Publications by category
Journal articles
Barbu MC, Amador C, Kwong A, Shen X, Adams M, Howard D, Walker R, Morris S, Min J, Liu C, et al (In Press). Complex Trait Methylation Risk Scores in the Prediction of Major Depressive Disorder.
van Dongen J, Hagenbeek FA, Suderman M, Roetman P, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty J, Adams MJ, et al (In Press). DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan.
Abstract:
DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan
AbstractDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2×10−7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Abstract.
Walker RM (In Press). Development and validation of DNA Methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes. Nature Aging
Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, Carnero-Montoro E, Lawson DJ, Burrows K, Suderman M, et al (In Press). Genomic and phenomic insights from an atlas of genetic effects on DNA methylation.
Abstract:
Genomic and phenomic insights from an atlas of genetic effects on DNA methylation
AbstractCharacterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.
Abstract.
Gao C, Amador C, Walker RM, Campbell A, Madden RA, Adams MJ, Bai X, Liu Y, Li M, Hayward C, et al (2023). Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans.
Genome Biology,
24(1).
Abstract:
Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans
Abstract
. Background
. The variation in the rate at which humans age may be rooted in early events acting through the genomic regions that are influenced by such events and subsequently are related to health phenotypes in later life. The parent-of-origin-effect (POE)-regulated methylome includes regions enriched for genetically controlled imprinting effects (the typical type of POE) and regions influenced by environmental effects associated with parents (the atypical POE). This part of the methylome is heavily influenced by early events, making it a potential route connecting early exposures, the epigenome, and aging. We aim to test the association of POE-CpGs with early and later exposures and subsequently with health-related phenotypes and adult aging.
.
. Results
. We perform a phenome-wide association analysis for the POE-influenced methylome using GS:SFHS (Ndiscovery = 5087, Nreplication = 4450). We identify and replicate 92 POE-CpG-phenotype associations. Most of the associations are contributed by the POE-CpGs belonging to the atypical class where the most strongly enriched associations are with aging (DNAmTL acceleration), intelligence, and parental (maternal) smoking exposure phenotypes. A proportion of the atypical POE-CpGs form co-methylation networks (modules) which are associated with these phenotypes, with one of the aging-associated modules displaying increased within-module methylation connectivity with age. The atypical POE-CpGs also display high levels of methylation heterogeneity, fast information loss with age, and a strong correlation with CpGs contained within epigenetic clocks.
.
. Conclusions
. These results identify the association between the atypical POE-influenced methylome and aging and provide new evidence for the “early development of origin” hypothesis for aging in humans.
.
Abstract.
Macdonald-Dunlop E, Taba N, Klarić L, Frkatović A, Walker R, Hayward C, Esko T, Haley C, Fischer K, Wilson JF, et al (2022). A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk.
Aging,
14(2), 623-659.
Abstract:
A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk
Biological age (BA), a measure of functional capacity and prognostic of health outcomes that discriminates between individuals of the same chronological age (chronAge), has been estimated using a variety of biomarkers. Previous comparative studies have mainly used epigenetic models (clocks), we use ~1000 participants to compare fifteen omics ageing clocks, with correlations of 0.21-0.97 with chronAge, even with substantial sub-setting of biomarkers. These clocks track common aspects of ageing with 95% of the variance in chronAge being shared among clocks. The difference between BA and chronAge - omics clock age acceleration (OCAA) - often associates with health measures. One year’s OCAA typically has the same effect on risk factors/10-year disease incidence as 0.09/0.25 years of chronAge. Epigenetic and IgG glycomics clocks appeared to track generalised ageing while others capture specific risks. We conclude BA is measurable and prognostic and that future work should prioritise health outcomes over chronAge.
Abstract.
Jung J, McCartney DL, Wagner J, Yoo J, Bell AS, Mavromatis LA, Rosoff DB, Hodgkinson CA, Sun H, Schwandt M, et al (2022). Additive Effects of Stress and Alcohol Exposure on Accelerated Epigenetic Aging in Alcohol Use Disorder. Biological Psychiatry, 93(4), 331-341.
Jung J, McCartney DL, Wagner J, Rosoff DB, Schwandt M, Sun H, Wiers CE, de Carvalho LM, Volkow ND, Walker RM, et al (2022). Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging. Molecular Psychiatry, 27(9), 3875-3884.
McCartney DL, Hillary RF, Conole ELS, Banos DT, Gadd DA, Walker RM, Nangle C, Flaig R, Campbell A, Murray AD, et al (2022). Blood-based epigenome-wide analyses of cognitive abilities. Genome Biology, 23(1).
Shen X, Caramaschi D, Adams MJ, Walker RM, Min JL, Kwong A, Hemani G, Genetics of DNA Methylation Consortium, Barbu MC, Whalley HC, et al (2022). DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses.
Genome Med,
14(1).
Abstract:
DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses.
BACKGROUND: Depression is a disabling and highly prevalent condition where genetic and epigenetic, such as DNA methylation (DNAm), differences contribute to disease risk. DNA methylation is influenced by genetic variation but the association between polygenic risk of depression and DNA methylation is unknown. METHODS: We investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N = 8898, mean age = 49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in the Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined = 2049, mean age = 79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N = 423, mean age = 17.1 years). Gene ontology analysis was conducted for the cytosine-guanine dinucleotide (CpG) probes significantly associated with depression PRS, followed by Mendelian randomisation (MR) analysis to infer the causal relationship between depression and DNAm. RESULTS: Widespread associations (NCpG = 71, pBonferroni < 0.05, p < 6.3 × 10-8) were found between PRS constructed using genetic risk variants for depression and DNAm in CpG probes that localised to genes involved in immune responses and neural development. The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r = 0.79) and in adolescents (r = 0.82). Gene Ontology analysis showed that significant CpG probes are enriched in immunological processes in the human leukocyte antigen system. Additional MWAS was conducted for each lead genetic risk variant. Over 47.9% of the independent genetic risk variants included in the PRS showed associations with DNAm in CpG probes located in both the same (cis) and distal (trans) locations to the genetic loci (pBonferroni < 0.045). Subsequent MR analysis showed that there are a greater number of causal effects found from DNAm to depression than vice versa (DNAm to depression: pFDR ranged from 0.024 to 7.45 × 10-30; depression to DNAm: pFDR ranged from 0.028 to 0.003). CONCLUSIONS: PRS for depression, especially those constructed from genome-wide significant genetic risk variants, showed methylome-wide differences associated with immune responses. Findings from MR analysis provided evidence for causal effect of DNAm to depression.
Abstract.
Author URL.
Lohoff F, Clarke T, Kaminsky ZA, Walker R, Bermingham M, Jung J, Morris S, Rosoff D, Barbu M, Charlet K, et al (2022). Epigenome-Wide Association Study of Alcohol Consumption in N=8161 Individuals and Relevance to Alcohol Use Disorder Pathophysiology. Biological Psychiatry, 91(9).
Hillary RF, Gadd DA, McCartney DL, Shi L, Campbell A, Walker RM, Ritchie CW, Deary IJ, Evans KL, Nevado‐Holgado AJ, et al (2022). Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer's disease implicate TBCA and TREM2 in disease risk. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 14(1).
Hillary RF, McCartney DL, McRae AF, Campbell A, Walker RM, Hayward C, Horvath S, Porteous DJ, Evans KL, Marioni RE, et al (2022). Identification of influential probe types in epigenetic predictions of human traits: implications for microarray design. Clinical Epigenetics, 14(1).
Gadd DA, Hillary RF, McCartney DL, Shi L, Stolicyn A, Robertson NA, Walker RM, McGeachan RI, Campbell A, Xueyi S, et al (2022). Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health. Nature Communications, 13(1).
Higham J, Kerr L, Zhang Q, Walker RM, Harris SE, Howard DM, Hawkins EL, Sandu A-L, Steele JD, Waiter GD, et al (2022). Local CpG density affects the trajectory and variance of age-associated DNA methylation changes. Genome Biology, 23(1).
Lee M, Joehanes R, McCartney DL, Kho M, Hüls A, Wyss AB, Liu C, Walker RM, Kardia SLR, Wingo TS, et al (2022). Opioid medication use and blood DNA methylation: epigenome-wide association meta-analysis. Epigenomics, 14(23), 1479-1492.
Sun Y-Q, Richmond RC, Suderman M, Min JL, Battram T, Flatberg A, Beisvag V, Nøst TH, Guida F, Jiang L, et al (2021). Assessing the role of genome-wide DNA methylation between smoking and risk of lung cancer using repeated measurements: the HUNT study. International Journal of Epidemiology, 50(5).
Bøstrand SMK, Vaher K, Nooij L, Harris MA, Cole JH, Cox SR, Marioni RE, McCartney DL, Walker RM, McIntosh AM, et al (2021). Associations between alcohol use and accelerated biological ageing. Addiction Biology, 27(1), e13100-e13100.
Stevenson AJ, Gadd DA, Hillary RF, McCartney DL, Campbell A, Walker RM, Evans KL, Harris SE, Spires-Jones TL, McRae AF, et al (2021). Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6. The Journals of Gerontology Series A, 76(12), 2284-2292.
van Dongen J, Hagenbeek FA, Suderman M, Roetman PJ, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty JD, Adams MJ, et al (2021). DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan.
Mol Psychiatry,
26(6), 2148-2162.
Abstract:
DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan.
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Abstract.
Author URL.
Lohoff FW, Clarke T-K, Kaminsky ZA, Walker RM, Bermingham ML, Jung J, Morris SW, Rosoff D, Campbell A, Barbu M, et al (2021). Epigenome-wide association study of alcohol consumption in N = 8161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine/glutamate transporter SLC7A11 as a top target. Molecular Psychiatry, 27(3), 1754-1764.
Barbu MC, Harris M, Shen X, Aleks S, Green C, Amador C, Walker R, Morris S, Adams M, Sandu A, et al (2021). Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study. Epigenetics, 17(10), 1143-1158.
McCartney DL, Min JL, Richmond RC, Lu AT, Sobczyk MK, Davies G, Broer L, Guo X, Jeong A, Jung J, et al (2021). Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
Genome Biol,
22(1).
Abstract:
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
Abstract.
Author URL.
Amador C, Zeng Y, Barber M, Walker RM, Campbell A, McIntosh AM, Evans KL, Porteous DJ, Hayward C, Wilson JF, et al (2021). Genome-wide methylation data improves dissection of the effect of smoking on body mass index. PLOS Genetics, 17(9).
Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, Carnero-Montoro E, Lawson DJ, Burrows K, Suderman M, et al (2021). Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
Nat Genet,
53(9), 1311-1321.
Abstract:
Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.
Abstract.
Author URL.
Walker RM, Vaher K, Bermingham ML, Morris SW, Bretherick AD, Zeng Y, Rawlik K, Amador C, Campbell A, Haley CS, et al (2021). Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles. Genome Medicine, 13(1).
Zeng Y, Amador C, Gao C, Walker RM, Morris SW, Campbell A, Frkatović A, Madden RA, Adams MJ, He S, et al (2021). Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome. EBioMedicine, 74
Gospodinova KO, Olsen D, Kaas M, Anderson SM, Phillips J, Walker RM, Bermingham ML, Payne AL, Giannopoulos P, Pandya D, et al (2021). Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks. Cellular and Molecular Neurobiology, 43(1), 237-249.
Schlosser P, Tin A, Matias-Garcia PR, Thio CHL, Joehanes R, Liu H, Weihs A, Yu Z, Hoppmann A, Grundner-Culemann F, et al (2021). Meta-analyses identify DNA methylation associated with kidney function and damage. Nature Communications, 12(1).
Barbu MC, Huider F, Campbell A, Amador C, Adams MJ, Lynall M-E, Howard DM, Walker RM, Morris SW, Van Dongen J, et al (2021). Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system. Molecular Psychiatry, 27(3), 1647-1657.
Howard DM, Pain O, Arathimos R, Barbu MC, Amador C, Walker RM, Jermy B, Adams MJ, Deary IJ, Porteous D, et al (2021). Methylome-wide association study of early life stressors and adult mental health. Human Molecular Genetics, 31(4).
Banos DT, McCartney DL, Patxot M, Anchieri L, Battram T, Christiansen C, Costeira R, Walker RM, Morris SW, Campbell A, et al (2020). Author Correction: Bayesian reassessment of the epigenetic architecture of complex traits. Nature Communications, 11(1).
Trejo Banos D, McCartney DL, Patxot M, Anchieri L, Battram T, Christiansen C, Costeira R, Walker RM, Morris SW, Campbell A, et al (2020). Bayesian reassessment of the epigenetic architecture of complex traits. Nature Communications, 11(1).
Madden RA, McCartney DL, Walker RM, Hillary RF, Bermingham ML, Rawlik K, Morris SW, Campbell A, Porteous DJ, Deary IJ, et al (2020). Birth weight associations with DNA methylation differences in an adult population. Epigenetics, 16(7), 783-796.
Stevenson AJ, McCartney DL, Hillary RF, Campbell A, Morris SW, Bermingham ML, Walker RM, Evans KL, Boutin TS, Hayward C, et al (2020). Characterisation of an inflammation-related epigenetic score and its association with cognitive ability. Clinical Epigenetics, 12(1).
Mur J, McCartney DL, Walker RM, Campbell A, Bermingham ML, Morris SW, Porteous DJ, McIntosh AM, Deary IJ, Evans KL, et al (2020). DNA methylation in APOE: the relationship with Alzheimer's and with cardiovascular health. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 6(1).
Seeboth A, McCartney DL, Wang Y, Hillary RF, Stevenson AJ, Walker RM, Campbell A, Evans KL, McIntosh AM, Hägg S, et al (2020). DNA methylation outlier burden, health, and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936. Clinical Epigenetics, 12(1).
Hillary RF, Stevenson AJ, McCartney DL, Campbell A, Walker RM, Howard DM, Ritchie CW, Horvath S, Hayward C, McIntosh AM, et al (2020). Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden. Clinical Epigenetics, 12(1).
Barbu MC, Shen X, Walker RM, Howard DM, Evans KL, Whalley HC, Porteous DJ, Morris SW, Deary IJ, Zeng Y, et al (2020). Epigenetic prediction of major depressive disorder. Molecular Psychiatry, 26(9), 5112-5123.
Lohoff F, Roy A, Jung J, Longley M, Rosoff D, Luo A, P'Connell E, Sorcher J, Sun H, Schwandt M, et al (2020). Epigenome-Wide Association Study and Multi-Tissue Replication of Individuals with Alcohol Use Disorder: Evidence for Abnormal Glucocorticoid Signaling Pathway Gene Regulation. Biological Psychiatry, 87(9).
Lohoff FW, Roy A, Jung J, Longley M, Rosoff DB, Luo A, O’Connell E, Sorcher JL, Sun H, Schwandt M, et al (2020). Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation. Molecular Psychiatry, 26(6), 2224-2237.
Walker RM, Bermingham ML, Vaher K, Morris SW, Clarke T, Bretherick AD, Zeng Y, Amador C, Rawlik K, Pandya K, et al (2020). Epigenome‐wide analyses identify DNA methylation signatures of dementia risk. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 12(1).
Langdon R, Richmond R, Elliott HR, Dudding T, Kazmi N, Penfold C, Ingarfield K, Ho K, Bretherick A, Haley C, et al (2020). Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer. Clinical Epigenetics, 12(1).
Green C, Shen X, Stevenson AJ, Conole ELS, Harris MA, Barbu MC, Hawkins EL, Adams MJ, Hillary RF, Lawrie SM, et al (2020). Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder. Brain Behavior and Immunity, 92, 39-48.
Clarke T, Morris SW, Walker R, Whalley H, Evans K, McIntosh A (2019). 17AN EPIGENOME-WIDE ASSOCIATION STUDY (EWAS) OF ALCOHOL CONSUMPTION REVEALS DNA METHYLATION SIGNATURES OF ALCOHOL USE. European Neuropsychopharmacology, 29, s1075-s1076.
Gibson J, Russ TC, Clarke T-K, Howard DM, Hillary RF, Evans KL, Walker RM, Bermingham ML, Morris SW, Campbell A, et al (2019). A meta-analysis of genome-wide association studies of epigenetic age acceleration. PLOS Genetics, 15(11).
Hamilton OKL, Zhang Q, McRae AF, Walker RM, Morris SW, Redmond P, Campbell A, Murray AD, Porteous DJ, Evans KL, et al (2019). An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort. International Journal of Obesity, 43(9), 1795-1802.
McCartney DL, Zhang F, Hillary RF, Zhang Q, Stevenson AJ, Walker RM, Bermingham ML, Boutin T, Morris SW, Campbell A, et al (2019). An epigenome-wide association study of sex-specific chronological ageing. Genome Medicine, 12(1).
Walker RM, MacGillivray L, McCafferty S, Wrobel N, Murphy L, Kerr SM, Morris SW, Campbell A, McIntosh AM, Porteous DJ, et al (2019). Assessment of dried blood spots for DNA methylation profiling. Wellcome Open Research, 4
Bressler J, Marioni RE, Walker RM, Xia R, Gottesman RF, Windham BG, Grove ML, Guan W, Pankow JS, Evans KL, et al (2019). Epigenetic Age Acceleration and Cognitive Function in African American Adults in Midlife: the Atherosclerosis Risk in Communities Study. The Journals of Gerontology Series A, 75(3), 473-480.
Bermingham ML, Walker RM, Marioni RE, Morris SW, Rawlik K, Zeng Y, Campbell A, Redmond P, Whalley HC, Adams MJ, et al (2019). Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD. EBioMedicine, 43, 576-586.
Zhang Q, Vallerga CL, Walker RM, Lin T, Henders AK, Montgomery GW, He J, Fan D, Fowdar J, Kennedy M, et al (2019). Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing. Genome Medicine, 11(1).
Barker V, Walker RM, Evans KL, Lawrie SM (2019). Methylation of glucocorticoid receptor (NR3C1), BDNF and oxytocin receptor genes in association with childhood maltreatment in schizophrenia and schizoaffective disorder. Schizophrenia Research, 216, 529-531.
Zeng Y, Amador C, Xia C, Marioni R, Sproul D, Walker RM, Morris SW, Bretherick A, Canela-Xandri O, Boutin TS, et al (2019). Parent of origin genetic effects on methylation in humans are common and influence complex trait variation. Nature Communications, 10(1).
Zeng Y, Amador C, Xia C, Marioni R, Sproul D, Walker RM, Morris SW, Bretherick A, Canela-Xandri O, Boutin TS, et al (2019). Publisher Correction: Parent of origin genetic effects on methylation in humans are common and influence complex trait variation. Nature Communications, 10(1).
Hafferty J, Adams M, Howard D, Clarke T, Morris SW, Bermingham M, Walker R, Marioni R, Campbell A, Nicodemus K, et al (2019). SA66EPIGENOME-WIDE ASSOCIATION STUDY OF ANTIDEPRESSANT USE. European Neuropsychopharmacology, 29
McIntosh A, Walker R, Marioni R, Deary IJ, Haley CS, Evans K, Whalley H (2019). SA8 ACCELERATED EPIGENETIC AGEING ASSOCIATED WITH MAJOR DEPRESSIVE DISORDER, NEUROTICISM, AND PSYCHOLOGICAL DISTRESS. European Neuropsychopharmacology, 29
McCartney DL, Walker RM, Morris SW, Anderson SM, Duff BJ, Marioni RE, Millar JK, McCarthy SE, Ryan NM, Lawrie SM, et al (2018). Altered DNA methylation associated with a translocation linked to major mental illness. Schizophrenia, 4(1).
Jovanova OS, Nedeljkovic I, Derek S, Walker RM, Liu C, Luciano M, Bressler J, Brody J, Drake AJ, Evans KL, et al (2018). DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies. JAMA Psychiatry, 75(9), 949-959.
McCartney DL, Hillary RF, Stevenson AJ, Ritchie SJ, Walker RM, Zhang Q, Morris SW, Bermingham ML, Campbell A, Murray AD, et al (2018). Epigenetic prediction of complex traits and death. Genome Biology, 19(1).
McCartney DL, Stevenson AJ, Hillary RF, Walker RM, Bermingham ML, Morris SW, Clarke T-K, Campbell A, Murray AD, Whalley HC, et al (2018). Epigenetic signatures of starting and stopping smoking. EBioMedicine, 37, 214-220.
McCartney DL, Stevenson AJ, Walker RM, Gibson J, Morris SW, Campbell A, Murray AD, Whalley HC, Porteous DJ, McIntosh AM, et al (2018). Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 10(1), 429-437.
Walker RM, Christoforou AN, McCartney DL, Morris SW, Kennedy NA, Morten P, Anderson SM, Torrance HS, Macdonald A, Sussmann JE, et al (2016). DNA methylation in a Scottish family multiply affected by bipolar disorder and major depressive disorder. Clinical Epigenetics, 8(1).
McCartney DL, Walker RM, Morris SW, McIntosh AM, Porteous DJ, Evans KL (2016). Identification of polymorphic and off-target probe binding sites on the Illumina Infinium MethylationEPIC BeadChip. Data in Brief, 9, 22-24.
Walker RM, Sussmann JE, Whalley HC, Ryan NM, Porteous DJ, McIntosh AM, Evans KL (2016). Preliminary assessment of pre‐morbid DNA methylation in individuals at high genetic risk of mood disorders. Bipolar Disorders, 18(5), 410-422.
Walker RM, Rybka J, Anderson SM, Torrance HS, Boxall R, Sussmann JE, Porteous DJ, McIntosh AM, Evans KL (2015). Preliminary investigation of miRNA expression in individuals at high familial risk of bipolar disorder. Journal of Psychiatric Research, 62, 48-55.
Rampino A, Walker RM, Torrance HS, Anderson SM, Fazio L, Di Giorgio A, Taurisano P, Gelao B, Romano R, Masellis R, et al (2014). Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia. PLOS ONE, 9(6).
Brown SM, Clapcote SJ, Millar JK, Torrance HS, Anderson SM, Walker R, Rampino A, Roder JC, Thomson PA, Porteous DJ, et al (2012). Erratum: Synaptic modulators Nrxn1 and Nrxn3 are disregulated in a Disc1 mouse model of schizophrenia. Molecular Psychiatry, 17(4), 469-469.
Walker RM, Hill AE, Newman AC, Hamilton G, Torrance HS, Anderson SM, Ogawa F, Derizioti P, Nicod J, Vernes SC, et al (2012). The DISC1 promoter: characterization and regulation by FOXP2. Human Molecular Genetics, 21(13), 2862-2872.
Brown SM, Clapcote SJ, Millar JK, Torrance HS, Anderson SM, Walker R, Rampino A, Roder JC, Thomson PA, Porteous DJ, et al (2011). Synaptic modulators Nrxn1 and Nrxn3 are disregulated in a Disc1 mouse model of schizophrenia. Molecular Psychiatry, 16(6), 585-587.
Walker RM, Christoforou A, Thomson PA, McGhee KA, Maclean A, Mühleisen TW, Strohmaier J, Nieratschker V, Nöthen MM, Rietschel M, et al (2010). Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder. Neuroscience Letters, 478(1), 9-13.
Sikka P, Walker R, Cockayne R, Wood MJA, Harrison PJ, Burnet PWJ (2010). D‐Serine metabolism in C6 glioma cells: Involvement of alanine‐serine‐cysteine transporter (ASCT2) and serine racemase (SRR) but not D‐amino acid oxidase (DAO). Journal of Neuroscience Research, 88(8), 1829-1840.
Pickard BS, Knight HM, Hamilton RS, Soares DC, Walker R, Boyd JKF, Machell J, Maclean A, McGhee KA, Condie A, et al (2008). A common variant in the 3′UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. Proceedings of the National Academy of Sciences of the United States of America, 105(39), 14940-14945.
Conferences
Shen X, Caramaschi D, Adams M, Walker R, Min JL, Kwong A, Barbu M, Whalley H, Harris S, Deary IJ, et al (2021). DNA METHYLOME-WIDE ASSOCIATION STUDY OF POLY-GENIC RISK SCORES FOR DEPRESSION IMPLICATING ANTIGEN PROCESSING AND IMMUNE RESPONSES.
Author URL.
van Dongen J, Hagenbeek FA, Suderman M, Roetman P, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty J, Adams MJ, et al (2020). DNA methylation signatures of a broad spectrum of aggressive behavior: a meta-analysis of epigenome-wide studies across the lifespan.
Author URL.
Publications by year
In Press
Barbu MC, Amador C, Kwong A, Shen X, Adams M, Howard D, Walker R, Morris S, Min J, Liu C, et al (In Press). Complex Trait Methylation Risk Scores in the Prediction of Major Depressive Disorder.
van Dongen J, Hagenbeek FA, Suderman M, Roetman P, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty J, Adams MJ, et al (In Press). DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan.
Abstract:
DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan
AbstractDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2×10−7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Abstract.
Walker RM (In Press). Development and validation of DNA Methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes. Nature Aging
Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, Carnero-Montoro E, Lawson DJ, Burrows K, Suderman M, et al (In Press). Genomic and phenomic insights from an atlas of genetic effects on DNA methylation.
Abstract:
Genomic and phenomic insights from an atlas of genetic effects on DNA methylation
AbstractCharacterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.
Abstract.
2023
Hillary RF, McCartney DL, Bernabeu E, Gadd DA, Cheng Y, Chybowska AD, Smith HM, Murphy L, Wrobel N, Campbell A, et al (2023). Blood-based epigenome-wide analyses on the prevalence and incidence of nineteen common disease states.
Gao C, Amador C, Walker RM, Campbell A, Madden RA, Adams MJ, Bai X, Liu Y, Li M, Hayward C, et al (2023). Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans.
Genome Biology,
24(1).
Abstract:
Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans
Abstract
. Background
. The variation in the rate at which humans age may be rooted in early events acting through the genomic regions that are influenced by such events and subsequently are related to health phenotypes in later life. The parent-of-origin-effect (POE)-regulated methylome includes regions enriched for genetically controlled imprinting effects (the typical type of POE) and regions influenced by environmental effects associated with parents (the atypical POE). This part of the methylome is heavily influenced by early events, making it a potential route connecting early exposures, the epigenome, and aging. We aim to test the association of POE-CpGs with early and later exposures and subsequently with health-related phenotypes and adult aging.
.
. Results
. We perform a phenome-wide association analysis for the POE-influenced methylome using GS:SFHS (Ndiscovery = 5087, Nreplication = 4450). We identify and replicate 92 POE-CpG-phenotype associations. Most of the associations are contributed by the POE-CpGs belonging to the atypical class where the most strongly enriched associations are with aging (DNAmTL acceleration), intelligence, and parental (maternal) smoking exposure phenotypes. A proportion of the atypical POE-CpGs form co-methylation networks (modules) which are associated with these phenotypes, with one of the aging-associated modules displaying increased within-module methylation connectivity with age. The atypical POE-CpGs also display high levels of methylation heterogeneity, fast information loss with age, and a strong correlation with CpGs contained within epigenetic clocks.
.
. Conclusions
. These results identify the association between the atypical POE-influenced methylome and aging and provide new evidence for the “early development of origin” hypothesis for aging in humans.
.
Abstract.
Gao C, Amador C, Walker RM, Campbell A, Madden RA, Adams MJ, Bai X, Liu Y, Li M, Hayward C, et al (2023). Phenome-wide analysis identifies parent-of-origin effects on the human methylome associated with changes in the rate of aging. , 4(01-27).
2022
Macdonald-Dunlop E, Taba N, Klarić L, Frkatović A, Walker R, Hayward C, Esko T, Haley C, Fischer K, Wilson JF, et al (2022). A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk.
Aging,
14(2), 623-659.
Abstract:
A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk
Biological age (BA), a measure of functional capacity and prognostic of health outcomes that discriminates between individuals of the same chronological age (chronAge), has been estimated using a variety of biomarkers. Previous comparative studies have mainly used epigenetic models (clocks), we use ~1000 participants to compare fifteen omics ageing clocks, with correlations of 0.21-0.97 with chronAge, even with substantial sub-setting of biomarkers. These clocks track common aspects of ageing with 95% of the variance in chronAge being shared among clocks. The difference between BA and chronAge - omics clock age acceleration (OCAA) - often associates with health measures. One year’s OCAA typically has the same effect on risk factors/10-year disease incidence as 0.09/0.25 years of chronAge. Epigenetic and IgG glycomics clocks appeared to track generalised ageing while others capture specific risks. We conclude BA is measurable and prognostic and that future work should prioritise health outcomes over chronAge.
Abstract.
Jung J, McCartney DL, Wagner J, Yoo J, Bell AS, Mavromatis LA, Rosoff DB, Hodgkinson CA, Sun H, Schwandt M, et al (2022). Additive Effects of Stress and Alcohol Exposure on Accelerated Epigenetic Aging in Alcohol Use Disorder. Biological Psychiatry, 93(4), 331-341.
Jung J, McCartney DL, Wagner J, Rosoff DB, Schwandt M, Sun H, Wiers CE, de Carvalho LM, Volkow ND, Walker RM, et al (2022). Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging. Molecular Psychiatry, 27(9), 3875-3884.
Lee L, Walker RM, Whiteley WN (2022). Assessing the role of vascular risk factors in dementia: Mendelian randomization meta-analysis and comparison with observational estimates.
Abstract:
Assessing the role of vascular risk factors in dementia: Mendelian randomization meta-analysis and comparison with observational estimates
Importance Although observational studies demonstrate that higher levels of vascular risk factors are associated with an increased risk of dementia, these associations might be explained by confounding or other biases. Mendelian randomization (MR) uses genetic instruments to test causal relationships in observational data. Objective to determine if genetically predicted modifiable risk factors (type 2 diabetes mellitus, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, body mass index, and circulating glucose) are associated with dementia by meta-analysing published MR studies. Secondary objectives were to identify heterogeneity in effect estimates across primary MR studies and to compare meta-analysis results with observational studies. Data sources MR studies identified by systematic search of Web of Science, OVID and Scopus. Study selection Primary MR studies investigating the modifiable risk factors of interest. Only one study from each cohort per risk factor was included. A quality assessment tool was developed to primarily assess the three assumptions of MR for each MR study. Data extraction and synthesis Data were extracted on study characteristics, exposure and outcome, effect estimates per unit increase, and measures of variation. Effect estimates were pooled to generate an overall estimate, I 2 and Cochrane Q values using fixed-effect model. Main outcomes and measures Odds ratio (OR) of developing dementia per standardized unit increase in the risk factor of interest. Results We screened 5211 studies and included 12 primary MR studies after applying inclusion and exclusion criteria. Higher genetically predicted body mass index was associated with a higher odds of dementia (OR 1.03 [1.01, 1.05] per 5 kg/m 2 increase, one study, p = 0.00285). Overall estimates from MR studies showed a smaller number of associations than those from meta-analyses of observational studies. Conclusion and relevance Genetically predicted body mass index was associated with an increase in risk of dementia. Key points Question Are genetically predicted modifiable risk factors associated with dementia? Findings Genetically predicted higher body mass index was associated with a higher odds of dementia. No evidence was found to support an association between genetically predicted type 2 diabetes mellitus, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, plasma glucose and dementia risk. Meaning Many modifiable risk factors associated with dementia in observational studies may not play a causative role.
Abstract.
McCartney DL, Hillary RF, Conole ELS, Banos DT, Gadd DA, Walker RM, Nangle C, Flaig R, Campbell A, Murray AD, et al (2022). Blood-based epigenome-wide analyses of cognitive abilities. Genome Biology, 23(1).
Barbu MC, Amador C, Kwong A, Shen X, Adams M, Howard D, Walker R, Morris S, Min J, Liu C, et al (2022). Complex Trait Methylation Risk Scores in the Prediction of Major Depressive Disorder.
Shen X, Caramaschi D, Adams MJ, Walker RM, Min JL, Kwong A, Hemani G, Genetics of DNA Methylation Consortium, Barbu MC, Whalley HC, et al (2022). DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses.
Genome Med,
14(1).
Abstract:
DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses.
BACKGROUND: Depression is a disabling and highly prevalent condition where genetic and epigenetic, such as DNA methylation (DNAm), differences contribute to disease risk. DNA methylation is influenced by genetic variation but the association between polygenic risk of depression and DNA methylation is unknown. METHODS: We investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N = 8898, mean age = 49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in the Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined = 2049, mean age = 79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N = 423, mean age = 17.1 years). Gene ontology analysis was conducted for the cytosine-guanine dinucleotide (CpG) probes significantly associated with depression PRS, followed by Mendelian randomisation (MR) analysis to infer the causal relationship between depression and DNAm. RESULTS: Widespread associations (NCpG = 71, pBonferroni < 0.05, p < 6.3 × 10-8) were found between PRS constructed using genetic risk variants for depression and DNAm in CpG probes that localised to genes involved in immune responses and neural development. The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r = 0.79) and in adolescents (r = 0.82). Gene Ontology analysis showed that significant CpG probes are enriched in immunological processes in the human leukocyte antigen system. Additional MWAS was conducted for each lead genetic risk variant. Over 47.9% of the independent genetic risk variants included in the PRS showed associations with DNAm in CpG probes located in both the same (cis) and distal (trans) locations to the genetic loci (pBonferroni < 0.045). Subsequent MR analysis showed that there are a greater number of causal effects found from DNAm to depression than vice versa (DNAm to depression: pFDR ranged from 0.024 to 7.45 × 10-30; depression to DNAm: pFDR ranged from 0.028 to 0.003). CONCLUSIONS: PRS for depression, especially those constructed from genome-wide significant genetic risk variants, showed methylome-wide differences associated with immune responses. Findings from MR analysis provided evidence for causal effect of DNAm to depression.
Abstract.
Author URL.
Chybowska AD, Gadd DA, Cheng Y, Bernabeu E, Campbell A, Walker RM, McIntosh AM, Wrobel N, Murphy L, Welsh P, et al (2022). Epigenetic contributions to clinical risk prediction of cardiovascular disease.
Hulls PM, McCartney DL, Bao Y, Walker RM, de Vocht F, Martin RM, Relton CL, Evans KL, Kumari M, Marioni RE, et al (2022). Epigenetic markers of adverse lifestyle identified among night shift workers.
Lohoff F, Clarke T, Kaminsky ZA, Walker R, Bermingham M, Jung J, Morris S, Rosoff D, Barbu M, Charlet K, et al (2022). Epigenome-Wide Association Study of Alcohol Consumption in N=8161 Individuals and Relevance to Alcohol Use Disorder Pathophysiology. Biological Psychiatry, 91(9).
Bretherick AD, Zeng Y, Walker RM, Hayward C, Porteous DJ, Evans KL, McIntosh AM, Baillie JK, Haley C, Ponting CP, et al (2022). Genetic control of KRAB-ZFP genes explains distal CpG-site methylation which associates with human disease phenotypes.
Hillary RF, Gadd DA, McCartney DL, Shi L, Campbell A, Walker RM, Ritchie CW, Deary IJ, Evans KL, Nevado‐Holgado AJ, et al (2022). Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer's disease implicate TBCA and TREM2 in disease risk. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 14(1).
Hillary RF, McCartney DL, McRae AF, Campbell A, Walker RM, Hayward C, Horvath S, Porteous DJ, Evans KL, Marioni RE, et al (2022). Identification of influential probe types in epigenetic predictions of human traits: implications for microarray design. Clinical Epigenetics, 14(1).
Gadd DA, Hillary RF, McCartney DL, Shi L, Stolicyn A, Robertson NA, Walker RM, McGeachan RI, Campbell A, Xueyi S, et al (2022). Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health. Nature Communications, 13(1).
Higham J, Kerr L, Zhang Q, Walker RM, Harris SE, Howard DM, Hawkins EL, Sandu A-L, Steele JD, Waiter GD, et al (2022). Local CpG density affects the trajectory and variance of age-associated DNA methylation changes. Genome Biology, 23(1).
Lee M, Joehanes R, McCartney DL, Kho M, Hüls A, Wyss AB, Liu C, Walker RM, Kardia SLR, Wingo TS, et al (2022). Opioid medication use and blood DNA methylation: epigenome-wide association meta-analysis. Epigenomics, 14(23), 1479-1492.
Hillary RF, McCartney DL, McRae AF, Campbell A, Walker RM, Hayward C, Horvath S, Porteous DJ, Evans KL, Marioni RE, et al (2022). The influence of biological and statistical properties of CpGs on epigenetic predictions of eighteen traits.
2021
Macdonald-Dunlop E, Taba N, Klaric L, Frkatovic A, Walker R, Hayward C, Esko T, Haley C, Fischer K, Wilson JF, et al (2021). A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk.
Sun Y-Q, Richmond RC, Suderman M, Min JL, Battram T, Flatberg A, Beisvag V, Nøst TH, Guida F, Jiang L, et al (2021). Assessing the role of genome-wide DNA methylation between smoking and risk of lung cancer using repeated measurements: the HUNT study. International Journal of Epidemiology, 50(5).
Bøstrand SMK, Vaher K, Nooij L, Harris MA, Cole JH, Cox SR, Marioni RE, McCartney DL, Walker RM, McIntosh AM, et al (2021). Associations between alcohol use and accelerated biological ageing. Addiction Biology, 27(1), e13100-e13100.
McCartney DL, Hillary RF, Conole ELS, Banos DT, Gadd DA, Walker RM, Nangle C, Flaig R, Campbell A, Murray ADD, et al (2021). Blood-based epigenome-wide analyses of cognitive abilities.
Stevenson AJ, Gadd DA, Hillary RF, McCartney DL, Campbell A, Walker RM, Evans KL, Harris SE, Spires-Jones TL, McRae AF, et al (2021). Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6. The Journals of Gerontology Series A, 76(12), 2284-2292.
Shen X, Caramaschi D, Adams M, Walker R, Min JL, Kwong A, Barbu M, Whalley H, Harris S, Deary IJ, et al (2021). DNA METHYLOME-WIDE ASSOCIATION STUDY OF POLY-GENIC RISK SCORES FOR DEPRESSION IMPLICATING ANTIGEN PROCESSING AND IMMUNE RESPONSES.
Author URL.
van Dongen J, Hagenbeek FA, Suderman M, Roetman PJ, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty JD, Adams MJ, et al (2021). DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan.
Mol Psychiatry,
26(6), 2148-2162.
Abstract:
DNA methylation signatures of aggression and closely related constructs: a meta-analysis of epigenome-wide studies across the lifespan.
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
Abstract.
Author URL.
Shen X, Caramaschi D, Adams MJ, Walker RM, Min JL, Kwong A, Hemani G, Consortium GODM, Barbu MC, Whalley HC, et al (2021). DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses.
Cheng Y, Gadd DA, Gieger C, Monterrubio-Gómez K, Zhang Y, Berta I, Stam MJ, Szlachetka N, Lobzaev E, Wrobel N, et al (2021). Development and validation of DNA Methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes.
Lohoff FW, Clarke T-K, Kaminsky ZA, Walker RM, Bermingham ML, Jung J, Morris SW, Rosoff D, Campbell A, Barbu M, et al (2021). Epigenome-wide association study of alcohol consumption in N = 8161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine/glutamate transporter SLC7A11 as a top target. Molecular Psychiatry, 27(3), 1754-1764.
Barbu MC, Harris M, Shen X, Aleks S, Green C, Amador C, Walker R, Morris S, Adams M, Sandu A, et al (2021). Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study. Epigenetics, 17(10), 1143-1158.
Hillary RF, Gadd DA, McCartney DL, Shi L, Campbell A, Walker RM, Ritchie CW, Deary IJ, Evans KL, Nevado-Holgado AJ, et al (2021). Genome and epigenome wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk.
McCartney DL, Min JL, Richmond RC, Lu AT, Sobczyk MK, Davies G, Broer L, Guo X, Jeong A, Jung J, et al (2021). Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
Genome Biol,
22(1).
Abstract:
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.
BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
Abstract.
Author URL.
Amador C, Zeng Y, Barber M, Walker RM, Campbell A, McIntosh AM, Evans KL, Porteous DJ, Hayward C, Wilson JF, et al (2021). Genome-wide methylation data improves dissection of the effect of smoking on body mass index. PLOS Genetics, 17(9).
Min JL, Hemani G, Hannon E, Dekkers KF, Castillo-Fernandez J, Luijk R, Carnero-Montoro E, Lawson DJ, Burrows K, Suderman M, et al (2021). Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
Nat Genet,
53(9), 1311-1321.
Abstract:
Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.
Abstract.
Author URL.
Walker RM, Vaher K, Bermingham ML, Morris SW, Bretherick AD, Zeng Y, Rawlik K, Amador C, Campbell A, Haley CS, et al (2021). Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles. Genome Medicine, 13(1).
Gadd DA, Hillary RF, McCartney DL, Shi L, Stolicyn A, Robertson N, Walker RM, McGeachan RI, Campbell A, Xueyi S, et al (2021). Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.
Zeng Y, Amador C, Gao C, Walker RM, Morris SW, Campbell A, Frkatović A, Madden RA, Adams MJ, He S, et al (2021). Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome. EBioMedicine, 74
Zeng Y, Amador C, Gao C, Walker RM, Morris SW, Campbell A, Frkatović A, Madden RA, Adams MJ, He S, et al (2021). Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome.
Higham J, Zhang Q, Walker RM, Harris SE, Howard DM, Hawkins EL, Sandu A-L, Steele JD, Waiter GD, Murray AD, et al (2021). Local CpG density affects the trajectory of age-associated epigenetic changes.
Gospodinova KO, Olsen D, Kaas M, Anderson SM, Phillips J, Walker RM, Bermingham ML, Payne AL, Giannopoulos P, Pandya D, et al (2021). Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks. Cellular and Molecular Neurobiology, 43(1), 237-249.
Gospodinova KO, Olsen D, Kaas M, Anderson SM, Phillips J, Walker RM, Bermingham ML, Payne AL, Giannopoulos P, Pandya D, et al (2021). Loss of SORCS2 is associated with neuronal DNA double-strand breaks.
Schlosser P, Tin A, Matias-Garcia PR, Thio CHL, Joehanes R, Liu H, Weihs A, Yu Z, Hoppmann A, Grundner-Culemann F, et al (2021). Meta-analyses identify DNA methylation associated with kidney function and damage. Nature Communications, 12(1).
Barbu MC, Huider F, Campbell A, Amador C, Adams MJ, Lynall M-E, Howard DM, Walker RM, Morris SW, Van Dongen J, et al (2021). Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system. Molecular Psychiatry, 27(3), 1647-1657.
Howard DM, Pain O, Arathimos R, Barbu MC, Amador C, Walker RM, Jermy B, Adams MJ, Deary IJ, Porteous D, et al (2021). Methylome-wide association study of early life stressors and adult mental health. Human Molecular Genetics, 31(4).
Howard DM, Pain O, Arathimos R, Barbu MC, Amador C, Walker RM, Jermy B, Adams MJ, Deary IJ, Porteous D, et al (2021). Methylome-wide association study of early life stressors and adult mental health reveals a relationship between birth date and cell type composition in blood.
2020
Bøstrand SMK, Vaher K, De Nooij L, Harris MA, Cole JH, Cox SR, Marioni RE, McCartney DL, Walker RM, McIntosh AM, et al (2020). Associations between alcohol use and accelerated biological ageing.
Banos DT, McCartney DL, Patxot M, Anchieri L, Battram T, Christiansen C, Costeira R, Walker RM, Morris SW, Campbell A, et al (2020). Author Correction: Bayesian reassessment of the epigenetic architecture of complex traits. Nature Communications, 11(1).
Trejo Banos D, McCartney DL, Patxot M, Anchieri L, Battram T, Christiansen C, Costeira R, Walker RM, Morris SW, Campbell A, et al (2020). Bayesian reassessment of the epigenetic architecture of complex traits. Nature Communications, 11(1).
Madden RA, McCartney DL, Walker RM, Hillary RF, Bermingham ML, Rawlik K, Morris SW, Campbell A, Porteous DJ, Deary IJ, et al (2020). Birth weight associations with DNA methylation differences in an adult population. Epigenetics, 16(7), 783-796.
Stevenson AJ, McCartney DL, Hillary RF, Campbell A, Morris SW, Bermingham ML, Walker RM, Evans KL, Boutin TS, Hayward C, et al (2020). Characterisation of an inflammation-related epigenetic score and its association with cognitive ability. Clinical Epigenetics, 12(1).
Stevenson AJ, Gadd DA, Hillary RF, McCartney DL, Campbell A, Walker RM, Evans KL, Harris SE, Spires-Jones TL, MacRae AF, et al (2020). Creating and validating a DNA methylation-based proxy for Interleukin-6.
Mur J, McCartney DL, Walker RM, Campbell A, Bermingham ML, Morris SW, Porteous DJ, McIntosh AM, Deary IJ, Evans KL, et al (2020). DNA methylation in APOE: the relationship with Alzheimer's and with cardiovascular health. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 6(1).
Seeboth A, McCartney DL, Wang Y, Hillary RF, Stevenson AJ, Walker RM, Campbell A, Evans KL, McIntosh AM, Hägg S, et al (2020). DNA methylation outlier burden, health, and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936. Clinical Epigenetics, 12(1).
Green C, Shen X, Stevenson AJ, Conole ELS, Harris MA, Barbu MC, Hawkins EL, Adams MJ, Lawrie SM, Evans KL, et al (2020). DNA methylation signatures of C-reactive protein associations with structural neuroimaging measures and major depressive disorder.
van Dongen J, Hagenbeek FA, Suderman M, Roetman P, Sugden K, Chiocchetti AG, Ismail K, Mulder RH, Hafferty J, Adams MJ, et al (2020). DNA methylation signatures of a broad spectrum of aggressive behavior: a meta-analysis of epigenome-wide studies across the lifespan.
Author URL.
Hillary RF, Stevenson AJ, McCartney DL, Campbell A, Walker RM, Howard DM, Ritchie CW, Horvath S, Hayward C, McIntosh AM, et al (2020). Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden.
Hillary RF, Stevenson AJ, McCartney DL, Campbell A, Walker RM, Howard DM, Ritchie CW, Horvath S, Hayward C, McIntosh AM, et al (2020). Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden. Clinical Epigenetics, 12(1).
Barbu MC, Shen X, Walker RM, Howard DM, Evans KL, Whalley HC, Porteous DJ, Morris SW, Deary IJ, Zeng Y, et al (2020). Epigenetic prediction of major depressive disorder. Molecular Psychiatry, 26(9), 5112-5123.
Gadd DA, Hillary RF, McCartney DL, Zaghlool SB, Stevenson AJ, Nangle C, Campbell A, Flaig R, Harris SE, Walker RM, et al (2020). Epigenetic scores for the circulating proteome as tools for disease prediction.
Lohoff F, Roy A, Jung J, Longley M, Rosoff D, Luo A, P'Connell E, Sorcher J, Sun H, Schwandt M, et al (2020). Epigenome-Wide Association Study and Multi-Tissue Replication of Individuals with Alcohol Use Disorder: Evidence for Abnormal Glucocorticoid Signaling Pathway Gene Regulation. Biological Psychiatry, 87(9).
Walker RM, Bermingham ML, Vaher K, Morris SW, Clarke T-K, Bretherick AD, Zeng Y, Amador C, Rawlik K, Pandya K, et al (2020). Epigenome-wide analyses identify DNA methylation signatures of dementia risk.
Lohoff FW, Roy A, Jung J, Longley M, Rosoff DB, Luo A, O’Connell E, Sorcher JL, Sun H, Schwandt M, et al (2020). Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation. Molecular Psychiatry, 26(6), 2224-2237.
Walker RM, Bermingham ML, Vaher K, Morris SW, Clarke T, Bretherick AD, Zeng Y, Amador C, Rawlik K, Pandya K, et al (2020). Epigenome‐wide analyses identify DNA methylation signatures of dementia risk. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 12(1).
McCartney DL, Min JL, Richmond RC, Lu AT, Sobczyk MK, Davies G, Broer L, Guo X, Jeong A, Jung J, et al (2020). Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing.
Amador C, Zeng Y, Barber M, Walker R, Campbell A, McIntosh AM, Evans KL, Porteous D, Hayward C, Wilson JF, et al (2020). Genome-wide methylation data improves dissection of the effect of smoking on body mass index.
Langdon R, Richmond R, Elliott HR, Dudding T, Kazmi N, Penfold C, Ingarfield K, Ho K, Bretherick A, Haley C, et al (2020). Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer. Clinical Epigenetics, 12(1).
Barbu M, Huider F, Campbell A, Amador C, Adams M, Lynall M, Howard D, Walker R, Morris S, Van Dongen J, et al (2020). Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system.
Green C, Shen X, Stevenson AJ, Conole ELS, Harris MA, Barbu MC, Hawkins EL, Adams MJ, Hillary RF, Lawrie SM, et al (2020). Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder. Brain Behavior and Immunity, 92, 39-48.
2019
Clarke T, Morris SW, Walker R, Whalley H, Evans K, McIntosh A (2019). 17AN EPIGENOME-WIDE ASSOCIATION STUDY (EWAS) OF ALCOHOL CONSUMPTION REVEALS DNA METHYLATION SIGNATURES OF ALCOHOL USE. European Neuropsychopharmacology, 29, s1075-s1076.
Gibson J, Russ TC, Clarke T-K, Howard DM, Hillary RF, Evans KL, Walker RM, Bermingham ML, Morris SW, Campbell A, et al (2019). A meta-analysis of genome-wide association studies of epigenetic age acceleration. PLOS Genetics, 15(11).
Gibson J, Russ TC, Clarke T-K, Howard DM, Evans KL, Walker RM, Bermingham ML, Morris SW, Campbell A, Hayward C, et al (2019). A meta-analysis of genome-wide association studies of epigenetic age acceleration.
Hamilton OKL, Zhang Q, McRae AF, Walker RM, Morris SW, Redmond P, Campbell A, Murray AD, Porteous DJ, Evans KL, et al (2019). An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort. International Journal of Obesity, 43(9), 1795-1802.
McCartney DL, Hillary RF, Zhang Q, Stevenson AJ, Walker RM, Bermingham ML, Morris SW, Campbell A, Murray AD, Whalley HC, et al (2019). An epigenome-wide association study of sex-specific chronological ageing.
McCartney DL, Zhang F, Hillary RF, Zhang Q, Stevenson AJ, Walker RM, Bermingham ML, Boutin T, Morris SW, Campbell A, et al (2019). An epigenome-wide association study of sex-specific chronological ageing. Genome Medicine, 12(1).
Walker RM, MacGillivray L, McCafferty S, Wrobel N, Murphy L, Kerr SM, Morris SW, Campbell A, McIntosh AM, Porteous DJ, et al (2019). Assessment of Dried Blood Spots for DNA Methylation Profiling.
Walker RM, MacGillivray L, McCafferty S, Wrobel N, Murphy L, Kerr SM, Morris SW, Campbell A, McIntosh AM, Porteous DJ, et al (2019). Assessment of dried blood spots for DNA methylation profiling. Wellcome Open Research, 4
Madden RA, McCartney DL, Walker RM, Hillary RF, Bermingham ML, Rawlik K, Morris SW, Campbell A, Porteous DJ, Deary IJ, et al (2019). Birth weight associations with psychiatric and physical health, cognitive function, and DNA methylation differences in an adult population.
Stevenson AJ, McCartney DL, Hillary RF, Campbell A, Morris SW, Bermingham ML, Walker RM, Evans KL, Boutin TS, Hayward C, et al (2019). Characterisation of an inflammation-related epigenetic score and its association with cognitive ability.
Mur J, McCartney DL, Walker RM, Campbell A, Bermingham ML, Morris SW, Porteous DJ, McIntosh AM, Deary IJ, Evans KL, et al (2019). DNA methylation in the APOE gene: its link with Alzheimer’s and cardiovascular health.
Seeboth A, McCartney DL, Wang Y, Hillary RF, Stevenson AJ, Walker RM, Evans KL, McIntosh AM, Hägg S, Deary IJ, et al (2019). DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936.
Bressler J, Marioni RE, Walker RM, Xia R, Gottesman RF, Windham BG, Grove ML, Guan W, Pankow JS, Evans KL, et al (2019). Epigenetic Age Acceleration and Cognitive Function in African American Adults in Midlife: the Atherosclerosis Risk in Communities Study. The Journals of Gerontology Series A, 75(3), 473-480.
Barbu MC, Walker RM, Howard DM, Evans KL, Whalley HC, Porteous DJ, Morris SW, Deary IJ, Marioni RE, Clarke T-K, et al (2019). Epigenetic prediction of major depressive disorder.
Walker RM, Vaher K, Bermingham ML, Morris SW, Bretherick AD, Zeng Y, Rawlik K, Amador C, Campbell A, Haley CS, et al (2019). Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2.
Bermingham ML, Walker RM, Marioni RE, Morris SW, Rawlik K, Zeng Y, Campbell A, Redmond P, Whalley HC, Adams MJ, et al (2019). Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD. EBioMedicine, 43, 576-586.
Langdon R, Richmond R, Elliott HR, Dudding T, Kazmi N, Penfold C, Ingarfield K, Ho K, Bretherick A, Haley C, et al (2019). Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer.
Zhang Q, Vallerga CL, Walker RM, Lin T, Henders AK, Montgomery GW, He J, Fan D, Fowdar J, Kennedy M, et al (2019). Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing. Genome Medicine, 11(1).
Barker V, Walker RM, Evans KL, Lawrie SM (2019). Methylation of glucocorticoid receptor (NR3C1), BDNF and oxytocin receptor genes in association with childhood maltreatment in schizophrenia and schizoaffective disorder. Schizophrenia Research, 216, 529-531.
Zeng Y, Amador C, Xia C, Marioni R, Sproul D, Walker RM, Morris SW, Bretherick A, Canela-Xandri O, Boutin TS, et al (2019). Parent of origin genetic effects on methylation in humans are common and influence complex trait variation. Nature Communications, 10(1).
Zeng Y, Amador C, Xia C, Marioni R, Sproul D, Walker RM, Morris SW, Bretherick A, Canela-Xandri O, Boutin TS, et al (2019). Publisher Correction: Parent of origin genetic effects on methylation in humans are common and influence complex trait variation. Nature Communications, 10(1).
Hafferty J, Adams M, Howard D, Clarke T, Morris SW, Bermingham M, Walker R, Marioni R, Campbell A, Nicodemus K, et al (2019). SA66EPIGENOME-WIDE ASSOCIATION STUDY OF ANTIDEPRESSANT USE. European Neuropsychopharmacology, 29
McIntosh A, Walker R, Marioni R, Deary IJ, Haley CS, Evans K, Whalley H (2019). SA8 ACCELERATED EPIGENETIC AGEING ASSOCIATED WITH MAJOR DEPRESSIVE DISORDER, NEUROTICISM, AND PSYCHOLOGICAL DISTRESS. European Neuropsychopharmacology, 29
2018
McCartney DL, Walker RM, Morris SW, Anderson SM, Duff BJ, Marioni RE, Millar JK, McCarthy SE, Ryan NM, Lawrie SM, et al (2018). Altered DNA methylation associated with a translocation linked to major mental illness. Schizophrenia, 4(1).
Hamilton OK, Zhang Q, McRae AF, Walker RM, Morris SW, Redmond P, Campbell A, Murray AD, Porteous DJ, Evans KL, et al (2018). An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort 1936.
Banos DT, McCartney DL, Battram T, Hemani G, Walker RM, Morris SW, Zhang Q, Porteous DJ, McRae AF, Wray NR, et al (2018). Bayesian reassessment of the epigenetic architecture of complex traits.
Jovanova OS, Nedeljkovic I, Derek S, Walker RM, Liu C, Luciano M, Bressler J, Brody J, Drake AJ, Evans KL, et al (2018). DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies. JAMA Psychiatry, 75(9), 949-959.
McCartney DL, Stevenson AJ, Walker RM, Gibson J, Morris SW, Campbell A, Murray AD, Whalley HC, Porteous DJ, McIntosh AM, et al (2018). DNA methylation age acceleration and risk factors for Alzheimer’s disease.
McCartney DL, Hillary RF, Stevenson AJ, Ritchie SJ, Walker RM, Zhang Q, Morris SW, Bermingham ML, Campbell A, Murray AD, et al (2018). Epigenetic prediction of complex traits and death. Genome Biology, 19(1).
McCartney DL, Stevenson AJ, Ritchie SJ, Walker RM, Zhang Q, Morris SW, Campbell A, Murray AD, Whalley HC, Gale CR, et al (2018). Epigenetic prediction of complex traits and death.
McCartney DL, Stevenson AJ, Hillary RF, Walker RM, Bermingham ML, Morris SW, Clarke T-K, Campbell A, Murray AD, Whalley HC, et al (2018). Epigenetic signatures of starting and stopping smoking. EBioMedicine, 37, 214-220.
McCartney DL, Stevenson AJ, Hillary RF, Walker RM, Bermingham ML, Morris SW, Clarke T-K, Campbell A, Murray AD, Whalley HC, et al (2018). Epigenetic signatures of starting and stopping smoking.
Bermingham ML, Walker RM, Marioni RE, Morris SM, Rawlik K, Zeng Y, Campbell A, Redmond P, Whalley HC, Adams MJ, et al (2018). Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD.
Zhang Q, Vallerga CL, Walker RM, Lin T, Henders AK, Montgomery GW, He J, Fan D, Fowdar J, Kennedy M, et al (2018). Improved prediction of chronological age from DNA methylation limits it as a biomarker of ageing.
McCartney DL, Stevenson AJ, Walker RM, Gibson J, Morris SW, Campbell A, Murray AD, Whalley HC, Porteous DJ, McIntosh AM, et al (2018). Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease. Alzheimer's & Dementia Diagnosis Assessment & Disease Monitoring, 10(1), 429-437.
2017
Whalley HC, Gibson J, Marioni R, Walker RM, Clarke T-K, Howard DM, Adams MJ, Hall L, Morris S, Deary IJ, et al (2017). Accelerated Epigenetic Ageing in Major Depressive Disorder.
2016
Walker RM, Christoforou AN, McCartney DL, Morris SW, Kennedy NA, Morten P, Anderson SM, Torrance HS, Macdonald A, Sussmann JE, et al (2016). DNA methylation in a Scottish family multiply affected by bipolar disorder and major depressive disorder. Clinical Epigenetics, 8(1).
McCartney DL, Walker RM, Morris SW, McIntosh AM, Porteous DJ, Evans KL (2016). Identification of polymorphic and off-target probe binding sites on the Illumina Infinium MethylationEPIC BeadChip. Data in Brief, 9, 22-24.
McCartney DL, Walker RM, Morris SW, McIntosh AM, Porteous DJ, Evans KL (2016). Identification of polymorphic and off-target probe binding sites on the Illumina Infinium MethylationEPIC BeadChip.
Walker RM, Sussmann JE, Whalley HC, Ryan NM, Porteous DJ, McIntosh AM, Evans KL (2016). Preliminary assessment of pre‐morbid DNA methylation in individuals at high genetic risk of mood disorders. Bipolar Disorders, 18(5), 410-422.
2015
Walker RM, Rybka J, Anderson SM, Torrance HS, Boxall R, Sussmann JE, Porteous DJ, McIntosh AM, Evans KL (2015). Preliminary investigation of miRNA expression in individuals at high familial risk of bipolar disorder. Journal of Psychiatric Research, 62, 48-55.
2014
Rampino A, Walker RM, Torrance HS, Anderson SM, Fazio L, Di Giorgio A, Taurisano P, Gelao B, Romano R, Masellis R, et al (2014). Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia. PLOS ONE, 9(6).
2012
Brown SM, Clapcote SJ, Millar JK, Torrance HS, Anderson SM, Walker R, Rampino A, Roder JC, Thomson PA, Porteous DJ, et al (2012). Erratum: Synaptic modulators Nrxn1 and Nrxn3 are disregulated in a Disc1 mouse model of schizophrenia. Molecular Psychiatry, 17(4), 469-469.
Walker RM, Hill AE, Newman AC, Hamilton G, Torrance HS, Anderson SM, Ogawa F, Derizioti P, Nicod J, Vernes SC, et al (2012). The DISC1 promoter: characterization and regulation by FOXP2. Human Molecular Genetics, 21(13), 2862-2872.
2011
Brown SM, Clapcote SJ, Millar JK, Torrance HS, Anderson SM, Walker R, Rampino A, Roder JC, Thomson PA, Porteous DJ, et al (2011). Synaptic modulators Nrxn1 and Nrxn3 are disregulated in a Disc1 mouse model of schizophrenia. Molecular Psychiatry, 16(6), 585-587.
2010
Walker RM, Christoforou A, Thomson PA, McGhee KA, Maclean A, Mühleisen TW, Strohmaier J, Nieratschker V, Nöthen MM, Rietschel M, et al (2010). Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder. Neuroscience Letters, 478(1), 9-13.
Sikka P, Walker R, Cockayne R, Wood MJA, Harrison PJ, Burnet PWJ (2010). D‐Serine metabolism in C6 glioma cells: Involvement of alanine‐serine‐cysteine transporter (ASCT2) and serine racemase (SRR) but not D‐amino acid oxidase (DAO). Journal of Neuroscience Research, 88(8), 1829-1840.
2008
Pickard BS, Knight HM, Hamilton RS, Soares DC, Walker R, Boyd JKF, Machell J, Maclean A, McGhee KA, Condie A, et al (2008). A common variant in the 3′UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. Proceedings of the National Academy of Sciences of the United States of America, 105(39), 14940-14945.