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Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Molecular Psychiatry volume 25, pages 1430–1446 (2020)Cite this article

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A Correction to this article was published on 18 May 2020

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Abstract

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094–92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10−7 versus rg = −0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10−4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

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References

  1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211–59.

    Google Scholar 

  2. McManus S, Bebbington P, Jenkins R, Brugha T. Mental health and wellbeing in England: Adult Psychiatric Morbidity Survey 2014: a survey carried out for NHS Digital by NatCen Social Research and the Department of Health Sciences, University of Leicester. NHS Digital, 2016.

  3. Green JG, McLaughlin KA, Berglund PA, Gruber MJ, Sampson NA, Zaslavsky AM, et al. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010;67:113–23.

    PubMed  PubMed Central  Google Scholar 

  4. Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry. 2012;169:141–51.

    PubMed  Google Scholar 

  5. Kessler RC. The effects of stressful life events on depression. Annu Rev Psychol. 1997;48:191–214.

    CAS  PubMed  Google Scholar 

  6. McLaughlin KA, Conron KJ, Koenen KC, Gilman SE. Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a population-based sample of adults. Psychol Med. 2010;40:1647–58.

    CAS  PubMed  Google Scholar 

  7. Kessler RC, Davis CG, Kendler KS. Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychol Med. 1997;27:1101–19.

    CAS  PubMed  Google Scholar 

  8. Collishaw S, Pickles A, Messer J, Rutter M, Shearer C, Maughan B. Resilience to adult psychopathology following childhood maltreatment: evidence from a community sample. Child Abus Negl. 2007;31:211–29.

    Google Scholar 

  9. Baldwin JR, Reuben A, Newbury JB, Danese A. Agreement between prospective and retrospective measures of childhood maltreatment: a systematic review and meta-analysis. JAMA Psychiatry. 2019. https://doi.org/10.1001/jamapsychiatry.2019.0097.

  10. Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry. 1999;156:837–41.

    CAS  PubMed  Google Scholar 

  11. Kendler KS, Karkowski-Shuman L. Stressful life events and genetic liability to major depression: genetic control of exposure to the environment? Psychol Med. 1997;27:539–47.

    CAS  PubMed  Google Scholar 

  12. Polderman TJC, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015;47:702–9.

    CAS  PubMed  Google Scholar 

  13. Yang J, Zeng J, Goddard ME, Wray NR, Visscher PM. Concepts, estimation and interpretation of SNP-based heritability. Nat Genet. 2017;49:1304–10.

    CAS  PubMed  Google Scholar 

  14. Hyde CL, Nagle MW, Tian C, Chen X, Paciga SA, Wendland JR, et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat Genet. 2016;48:1031–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018;50:668–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Jang KL, Vernon PA, Livesley WJ, Stein MB, Wolf H. Intra- and extra-familial influences on alcohol and drug misuse: a twin study of gene-environment correlation. Addiction. 2001;96:1307–18.

    CAS  PubMed  Google Scholar 

  17. Stein MB, Jang KL, Taylor S, Vernon PA, Livesley WJ. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. Am J Psychiatry. 2002;159:1675–81.

    PubMed  Google Scholar 

  18. Lyons MJ, Goldberg J, Eisen SA, True W, Tsuang MT, Meyer JM, et al. Do genes influence exposure to trauma? A twin study of combat. Am J Med Genet. 1993;48:22–7.

    CAS  PubMed  Google Scholar 

  19. Power RA, Wingenbach T, Cohen-Woods S, Uher R, Ng MY, Butler AW, et al. Estimating the heritability of reporting stressful life events captured by common genetic variants. Psychol Med. 2013;43:1965–71.

    CAS  PubMed  Google Scholar 

  20. Dunn EC, Brown RC, Dai Y, Rosand J, Nugent NR, Amstadter AB, et al. Genetic determinants of depression: recent findings and future directions. Harv Rev Psychiatry. 2015;23:1–18.

    PubMed  PubMed Central  Google Scholar 

  21. Schraedley PK, Turner RJ, Gotlib IH. Stability of retrospective reports in depression: traumatic events, past depressive episodes, and parental psychopathology. J Health Soc Behav. 2002;43:307–16.

    PubMed  Google Scholar 

  22. Dunn EC, Wiste A, Radmanesh F, Almli LM, Gogarten SM, Sofer T, et al. Genome-wide association study (GWAS) and genome-wide by environment interaction study (GWEIS) of depressive symptoms in african american and hispanic/latina women. Depress Anxiety. 2016;33:265–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Peterson RE, Cai N, Dahl AW, Bigdeli TB, Edwards AC, Webb BT, et al. Molecular genetic analysis subdivided by adversity exposure suggests etiologic heterogeneity in major depression. Am J Psychiatry. 2018;175:545–54.

    PubMed  PubMed Central  Google Scholar 

  24. Peyrot WJ, Milaneschi Y, Abdellaoui A, Sullivan PF, Hottenga JJ, Boomsma DI, et al. Effect of polygenic risk scores on depression in childhood trauma. Br J Psychiatry. 2014;205:113–9.

    PubMed  PubMed Central  Google Scholar 

  25. Mullins N, Power RA, Fisher HL, Hanscombe KB, Euesden J, Iniesta R, et al. Polygenic interactions with environmental adversity in the aetiology of major depressive disorder. Psychol Med. 2016;46:759–70.

    CAS  PubMed  Google Scholar 

  26. Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PAF, Sullivan PF et al. Does childhood trauma moderate polygenic risk for depression? A meta-analysis of 5765 subjects from the Psychiatric Genomics Consortium. Biol Psychiatry. 2017. https://doi.org/10.1016/j.biopsych.2017.09.009.

  27. Jaffee SR, Price TS. Gene-environment correlations: a review of the evidence and implications for prevention of mental illness. Mol Psychiatry. 2007;12:432–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lau JYF, Eley TC. Disentangling gene-environment correlations and interactions on adolescent depressive symptoms. J Child Psychol Psychiatry. 2008;49:142–50.

    PubMed  Google Scholar 

  29. Thapar A, Harold G, McGuffin P. Life events and depressive symptoms in childhood–shared genes or shared adversity? A research note. J Child Psychol Psychiatry. 1998;39:1153–8.

    CAS  PubMed  Google Scholar 

  30. Boardman JD, Alexander KB, Stallings MC. Stressful life events and depression among adolescent twin pairs. Biodemogr Soc Biol. 2011;57:53–66.

    Google Scholar 

  31. Davis KAS, Coleman JRI, Adams M, Allen N, Breen G, Cullen B, et al. Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants. BJPsych Open. 2018;4:83–90.

    PubMed  PubMed Central  Google Scholar 

  32. Allen NE, Sudlow C, Peakman T, Collins R, Biobank UK. UK biobank data: come and get it. Sci Transl Med. 2014;6:224ed4.

    PubMed  Google Scholar 

  33. Smith DJ, Nicholl BI, Cullen B, Martin D, Ul-Haq Z, Evans J, et al. Prevalence and characteristics of probable major depression and bipolar disorder within UK biobank: cross-sectional study of 172,751 participants. PLoS One. 2013;8:e75362.

    PubMed  PubMed Central  Google Scholar 

  34. Bellis MA, Hughes K, Leckenby N, Perkins C, Lowey H. National household survey of adverse childhood experiences and their relationship with resilience to health-harming behaviors in England. BMC Med. 2014;12:72.

    PubMed  PubMed Central  Google Scholar 

  35. Bernstein DP, Fink L, Handelsman L, Foote J, Lovejoy M, Wenzel K, et al. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry. 1994;151:1132–6.

    CAS  PubMed  Google Scholar 

  36. Grabe HJ, Schulz A, Schmidt CO, Appel K, Driessen M, Wingenfeld K, et al. A brief instrument for the assessment of childhood abuse and neglect: the childhood trauma screener (CTS). Psychiatr Prax. 2012;39:109–15.

    PubMed  Google Scholar 

  37. Townsend P, Phillimore P, Beattie A. Health and deprivation: inequality and the north. London: Croom Helm; 1988.

  38. Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR, Teumer A, et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016;48:1279–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Walter K, Min JL. UK10K Consortium et al. The UK10K project identifies rare variants in health and disease. Nature. 526:82–90.

  41. Manichaikul A, Mychaleckyj JC, Rich SS, Daly K, Sale M, Chen W-M. Robust relationship inference in genome-wide association studies. Bioinformatics. 2010;26:2867–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, et al. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat Genet. 2017;49:403–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Abraham G, Qiu Y, Inouye M. FlashPCA2: principal component analysis of Biobank-scale genotype datasets. Bioinformatics. 2017;33:2776–8.

    CAS  PubMed  Google Scholar 

  44. Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genet Epidemiol. 2008;32:227–34.

    PubMed  PubMed Central  Google Scholar 

  45. Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:7.

    PubMed  PubMed Central  Google Scholar 

  46. Lloyd-Jones LR, Robinson MR, Yang J, Visscher PM. Transformation of summary statistics from linear mixed model association on all-or-none traits to odds ratio. Genetics. 2018. https://doi.org/10.1534/genetics.117.300360.

  47. Marioni RE, Harris SE, Zhang Q, McRae AF, Hagenaars SP, Hill WD, et al. GWAS on family history of Alzheimer’s disease. Transl Psychiatry. 2018;8:99.

    PubMed  PubMed Central  Google Scholar 

  48. Team RC. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2014. 2014.

  49. Loh P-R, Kichaev G, Gazal S, Schoech AP, Price AL. Mixed-model association for biobank-scale datasets. Nat Genet. 2018;50:906–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Lee SH, Goddard ME, Wray NR, Visscher PM. A better coefficient of determination for genetic profile analysis. Genet Epidemiol. 2012;36:214–24.

    PubMed  Google Scholar 

  51. Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Schizophrenia Working Group of the Psychiatric Genomics Consortium. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47:291–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Loh P-R, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47:1236–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Daniel WW and Cross CL. Biostatistics: A Foundation for Analysis in the Health Sciences, 11th ed.  Hoboken, NJ: John Wiley & Sons; 2018.

  54. Tukey WJ. Bias and confidence in not-quite large samples. Ann Math Stat. 1958;29:614.

    Google Scholar 

  55. Quenouille MH. Notes on bias in estimation. Biometrika. 1956;43:353–60.

    Google Scholar 

  56. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–7.

    PubMed Central  Google Scholar 

  57. Psychiatric GWAS Consortium Bipolar Disorder Working Group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet. 2011;43:977–83.

    Google Scholar 

  58. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Soranzo N, Sanna S, Wheeler E, Gieger C, Radke D, Dupuis J, et al. Common variants at 10 genomic loci influence hemoglobin A1(C) levels via glycemic and nonglycemic pathways. Diabetes. 2010;59:3229–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Euesden J, Lewis CM, O’Reilly PF. PRSice: Polygenic Risk Score software. Bioinformatics. 2015;31:1466–8.

    CAS  PubMed  Google Scholar 

  61. Choi SW, O’Reilly PF PRSice-2: Polygenic Risk Score software for biobank-scale data. Gigascience. 2019;8. https://doi.org/10.1093/gigascience/giz082.

  62. Keller MC. Gene × environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution. Biol Psychiatry. 2014;75:18–24.

    PubMed  Google Scholar 

  63. Yzerbyt VY, Muller D, Judd CM. Adjusting researchers’ approach to adjustment: on the use of covariates when testing interactions. J Exp Soc Psychol. 2004;40:424–31.

    Google Scholar 

  64. Turley P, Walters RK, Maghzian O, Okbay A, Lee JJ, Fontana MA et al. Multi-trait analysis of genome-wide association summary statistics using MTAG. Nat Genet. 2018;50:229–37.

  65. Howard DM, Adams MJ, Shirali M, Clarke T-K, Marioni RE, Davies G, et al. Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nat Commun. 2018;9:1470.

    PubMed  PubMed Central  Google Scholar 

  66. Smith DJ, Escott-Price V, Davies G, Bailey MES, Colodro-Conde L, Ward J, et al. Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci. Mol Psychiatry. 2016;21:749–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Luciano M, Hagenaars SP, Davies G, Hill WD, Clarke T-K, Shirali M, et al. Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism. Nat Genet. 2018;50:6–11.

    CAS  PubMed  Google Scholar 

  68. Okbay A, Baselmans BML, De Neve J-E, Turley P, Nivard MG, Fontana MA, et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat Genet. 2016;48:624–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Nagel M, Jansen PR, Stringer S, Watanabe K, de Leeuw CA, Bryois J, et al. Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways. Nat Genet. 2018;50:920–7.

    CAS  PubMed  Google Scholar 

  70. Weissbrod O, Flint J, Rosset S. Estimating SNP-based heritability and genetic correlation in case-control studies directly and with summary statistics. Am J Hum Genet. 2018;103:89–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Golan D, Lander ES, Rosset S. Measuring missing heritability: inferring the contribution of common variants. Proc Natl Acad Sci USA. 2014;111:E5272–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Munafò MR, Tilling K, Taylor AE, Evans DM, Davey Smith G. Collider scope: when selection bias can substantially influence observed associations. Int J Epidemiol. 2018;47:226–35.

    PubMed  Google Scholar 

  73. Fry A, Littlejohns TJ, Sudlow C, Doherty N, Allen NE. OP41 The representativeness of the UK Biobank cohort on a range of sociodemographic, physical, lifestyle and health-related characteristics. J Epidemiol Community Health. 2016;70:A26–A26.

    Google Scholar 

  74. Martin AR, Gignoux CR, Walters RK, Wojcik GL, Neale BM, Gravel S, et al. Human demographic history impacts genetic risk prediction across diverse populations. Am J Hum Genet. 2017;100:635–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Haro JM, Arbabzadeh-Bouchez S, Brugha TS, de Girolamo G, Guyer ME, Jin R, et al. Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health surveys. Int J Methods Psychiatr Res. 2006;15:167–80.

    PubMed  PubMed Central  Google Scholar 

  76. Kessler RC, Wittchen H-U, Abelson JM, Mcgonagle K, Schwarz N, Kendler KS, et al. Methodological studies of the Composite International Diagnostic Interview (CIDI) in the US national comorbidity survey (NCS). Int J Methods Psychiatr Res. 1998;7:33–55.

    Google Scholar 

  77. Nusslock R, Alloy LB. Reward processing and mood-related symptoms: an RDoC and translational neuroscience perspective. J Affect Disord. 2017;216:3–16.

    PubMed  PubMed Central  Google Scholar 

  78. Meehl PE. Schizotaxia, schizotypy, schizophrenia. Am Psychol. 1962;17:827–38.

    Google Scholar 

  79. Bleuler M. Conception of schizophrenia within the last fifty years and today [abridged]. Proc R Soc Med. 1963;56:945.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Rosenthal D. A suggested conceptual framework. In: Rosenthal D editor. The Genain quadruplets: a case study and theoretical analysis of heredity and environment in schizophrenia. New York, NY, US: Basic Books, xiv; 1963, p. 505–11.

  81. Nussey DH, Wilson AJ, Brommer JE. The evolutionary ecology of individual phenotypic plasticity in wild populations. J Evol Biol. 2007;20:831–44.

    CAS  PubMed  Google Scholar 

  82. Wright AGC, Simms LJ. Stability and fluctuation of personality disorder features in daily life. J Abnorm Psychol. 2016;125:641–56.

    PubMed  PubMed Central  Google Scholar 

  83. Fuemmeler BF, Dedert E, McClernon FJ, Beckham JC. Adverse childhood events are associated with obesity and disordered eating: results from a U.S. population-based survey of young adults. J Trauma Stress. 2009;22:329–33.

    PubMed  PubMed Central  Google Scholar 

  84. Metzler M, Merrick MT, Klevens J, Ports KA, Ford DC. Adverse childhood experiences and life opportunities: shifting the narrative. Child Youth Serv Rev. 2017;72:141–9.

    Google Scholar 

  85. Jaffee SR, Ambler A, Merrick M, Goldman-Mellor S, Odgers CL, Fisher HL, et al. Childhood maltreatment predicts poor economic and educational outcomes in the transition to adulthood. Am J Public Health. 2018;108:1142–7.

    PubMed  PubMed Central  Google Scholar 

  86. Danese A, Tan M. Childhood maltreatment and obesity: systematic review and meta-analysis. Mol Psychiatry. 2014;19:544–54.

    CAS  PubMed  Google Scholar 

  87. Cross-Disorder Group of the Psychiatric Genomics Consortium Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013;381:1371.

    PubMed Central  Google Scholar 

  88. Hill WD, Hagenaars SP, Marioni RE, Harris SE, Liewald DCM, Davies G, et al. Molecular genetic contributions to social deprivation and household income in UK Biobank. Curr Biol. 2016;26:3083–9.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the members of the UK Biobank Mental Health Genetics Group for their valuable discussion and feedback on this work. We are also deeply indebted to the scientists involved in the construction of the UK Biobank, and to the investigators who comprise the PGC. Finally, we thank the hundreds of thousands of subjects who have shared their life experiences with investigators in the UK Biobank and the PGC. This research has been conducted using the UK Biobank Resource, as an approved extension to application 16577 (Dr Breen). This study represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. High performance computing facilities were funded with capital equipment grants from the GSTT Charity (TR130505) and Maudsley Charity (980). WJP was funded by NWO Veni grant 91619152. KLP acknowledges funding from the Alexander von Humboldt Foundation. KWC was funded in part by the National Institute of Mental Health (T32MH017119). NRW acknowledges funding from the Australian National Health and Medical Research Council (1078901 and 1087889). PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320).

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Naomi R. Wray17,18, Stephan Ripke19,20,21, Manuel Mattheisen22,23,24, Maciej Trzaskowski17, Enda M. Byrne17, Abdel Abdellaoui25, Mark J. Adams26, Esben Agerbo27,28,29, Tracy M. Air30, Till F. M. Andlauer31,32, Silviu-Alin Bacanu33, Marie Bækvad-Hansen29,34, Aartjan T. F. Beekman35, Tim B. Bigdeli33,36, Elisabeth B. Binder31,37, Julien Bryois38, Henriette N. Buttenschøn29,39,40, Jonas Bybjerg-Grauholm29,34, Na Cai41,42, Enrique Castelao43, Jane Hvarregaard Christensen24,29,40, Toni-Kim Clarke26, Jonathan R. I. Coleman44, Lucía Colodro-Conde45, Baptiste Couvy-Duchesne18,46, Nick Craddock47, Gregory E. Crawford48,49, Gail Davies50, Ian J. Deary50, Franziska Degenhardt51, Eske M. Derks45, Nese Direk52,53, Conor V. Dolan25, Erin C. Dunn54,55,56, Thalia C. Eley44, Valentina Escott-Price57, Farnush Farhadi Hassan Kiadeh58, Hilary K. Finucane59,60, Jerome C. Foo61, Andreas J. Forstner51,62,63,64, Josef Frank61, Héléna A. Gaspar44, Michael Gill65, Fernando S. Goes66, Scott D. Gordon45, Jakob Grove24,29,40,67, Lynsey S. Hall26,68, Christine Søholm Hansen29,34, Thomas F. Hansen69,70,71, Stefan Herms51,63, Ian B. Hickie72, Per Hoffmann51,63, Georg Homuth73, Carsten Horn74, Jouke-Jan Hottenga25, David M. Hougaard29, David M. Howard26,44, Marcus Ising75, Rick Jansen35, Ian Jones76, Lisa A. Jones77, Eric Jorgenson78, James A. Knowles79, Isaac S. Kohane80,81,82, Julia Kraft20, Warren W. Kretzschmar83, Zoltán Kutalik84,85, Yihan Li83, Penelope A. Lind45, Donald J. MacIntyre86,87, Dean F. MacKinnon66, Robert M. Maier18, Wolfgang Maier88, Jonathan Marchini89, Hamdi Mbarek25 Patrick McGrath90, Peter McGuffin44, Sarah E. Medland45, Divya Mehta18,91, Christel M. Middeldorp25,92,93, Evelin Mihailov94, Yuri Milaneschi35, Lili Milani94, Francis M. Mondimore66, Grant W. Montgomery17, Sara Mostafavi95,96, Niamh Mullins44, Matthias Nauck97,98, Bernard Ng96, Michel G. Nivard25, Dale R. Nyholt99, Paul F. O’Reilly44, Hogni Oskarsson100, Michael J. Owen76, Jodie N. Painter45, Carsten Bøcker Pedersen27,28,29, Marianne Giørtz Pedersen27,28,29, Roseann E. Peterson33,101, Erik Pettersson38, Wouter J. Peyrot35, Giorgio Pistis43, Danielle Posthuma102,103, Jorge A. Quiroz104, Per Qvist24,29,40, John P. Rice105, Brien P. Riley33, Margarita Rivera44,106, Saira Saeed Mirza52, Robert Schoevers107, Eva C. Schulte108,109, Ling Shen78, Jianxin Shi110, Stanley I. Shyn111, Engilbert Sigurdsson112, Grant C. B. Sinnamon113, Johannes H. Smit35, Daniel J. Smith114, Hreinn Stefansson115, Stacy Steinberg115, Fabian Streit61, Jana Strohmaier61, Katherine E. Tansey116, Henning Teismann117, Alexander Teumer118, Wesley Thompson29,70,119,120, Pippa A. Thomson121, Thorgeir E. Thorgeirsson115, Matthew Traylor122, Jens Treutlein61, Vassily Trubetskoy20, Andrés G. Uitterlinden123, Daniel Umbricht124, Sandra Van der Auwera125, Albert M. van Hemert126, Alexander Viktorin38, Peter M. Visscher17,18, Yunpeng Wang29,70,120, Bradley T. Webb127, Shantel Marie Weinsheimer29,70, Jürgen Wellmann117, Gonneke Willemsen25, Stephanie H. Witt61, Yang Wu17, Hualin S. Xi128, Jian Yang18,129, Futao Zhang17, Volker Arolt130, Bernhard T. Baune131,132,133, Klaus Berger117, Dorret I. Boomsma25, Sven Cichon51,63,134,135, Udo Dannlowski130, E. J. C. de Geus25,136, J. Raymond DePaulo66, Enrico Domenici137, Katharina Domschke138,139, Tõnu Esko21,94, Hans J. Grabe125, Steven P. Hamilton140, Caroline Hayward141, Andrew C. Heath105, Kenneth S. Kendler33, Stefan Kloiber75,142,143, Glyn Lewis144, Qingqin S. Li145, Susanne Lucae75, Pamela A. F. Madden105, Patrik K. Magnusson38, Nicholas G. Martin45, Andrew M. McIntosh26,50, Andres Metspalu94,146, Ole Mors29,147, Preben Bo Mortensen27,28,29,40, Bertram Müller-Myhsok31,148,149, Merete Nordentoft29,150, Markus M. Nöthen51, Michael C. O’Donovan76, Sara A. Paciga151, Nancy L. Pedersen38, Brenda W. J. H. Penninx35, Roy H. Perlis54,152, David J. Porteous121, James B. Potash153, Martin Preisig43, Marcella Rietschel61, Catherine Schaefer78, Thomas G. Schulze61,109,154,155,156, Jordan W. Smoller54,55,56, Kari Stefansson115,157, Henning Tiemeier52,158,159, Rudolf Uher160, Henry Völzke118, Myrna M. Weissman90,161, Thomas Werge29,70,162, Cathryn M. Lewis44,163, Douglas F. Levinson164, Gerome Breen44,165, Anders D. Børglum24,29,40, Patrick F. Sullivan38,166,167

Author information

Authors and Affiliations

  1. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Jonathan R. I. Coleman, Kirstin L. Purves, Christopher Rayner, Shing Wan Choi, Christopher Hübel, Héléna A. Gaspar, Evangelos Vassos, Andrea Danese, Barbara Maughan, Cathryn M. Lewis, Paul F. O’Reilly, Thalia C. Eley & Gerome Breen

  2. NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK

    Jonathan R. I. Coleman, Katrina A. S. Davis, Christopher Hübel, Héléna A. Gaspar, Evangelos Vassos, Cathryn M. Lewis, Matthew Hotopf, Thalia C. Eley & Gerome Breen

  3. Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Medical Center, Amsterdam, the Netherlands

    Wouter J. Peyrot

  4. Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Katrina A. S. Davis, Carol Kan & Matthew Hotopf

  5. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

    Sandra Van der Auwera & Hans J. Grabe

  6. Division of Psychiatry, University of Edinburgh, Edinburgh, UK

    Mark James Adams & Andrew M. McIntosh

  7. Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

    Donald M. Lyall & Daniel J. Smith

  8. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    Karmel W. Choi

  9. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Karmel W. Choi

  10. Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, MA, USA

    Karmel W. Choi & Erin C. Dunn

  11. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

    Karmel W. Choi & Erin C. Dunn

  12. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Erin C. Dunn

  13. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Andrea Danese

  14. National and Specialist CAMHS Trauma and Anxiety Clinic, South London and Maudsley NHS Foundation Trust, London, UK

    Andrea Danese

  15. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

    Naomi R. Wray

  16. Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia

    Naomi R. Wray

  17. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

    Naomi R Wray, Maciej Trzaskowski, Enda M Byrne, Grant W Montgomery, Peter M Visscher, Yang Wu & Futao Zhang

  18. Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia

    Naomi R Wray, Baptiste Couvy-Duchesne, Robert M Maier, Divya Mehta, Peter M Visscher & Jian Yang

  19. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

    Stephan Ripke

  20. Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany

    Stephan Ripke, Julia Kraft & Vassily Trubetskoy

  21. Medical and Population Genetics, Broad Institute, Cambridge, MA, USA

    Stephan Ripke & Tõnu Esko

  22. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wurzburg, Wurzburg, Germany

    Manuel Mattheisen

  23. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Manuel Mattheisen

  24. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Manuel Mattheisen, Jane Hvarregaard Christensen, Jakob Grove, Per Qvist & Anders D Børglum

  25. Dept of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    Abdel Abdellaoui, Conor V Dolan, Jouke-Jan Hottenga, Hamdi Mbarek, Christel M Middeldorp, Michel G Nivard, Gonneke Willemsen, Dorret I Boomsma & E. J. C de Geus

  26. Division of Psychiatry, University of Edinburgh, Edinburgh, Scotland

    Mark J Adams, Toni-Kim Clarke, Lynsey S Hall, David M Howard & Andrew M McIntosh

  27. Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark

    Esben Agerbo, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen & Preben Bo Mortensen

  28. National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    Esben Agerbo, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen & Preben Bo Mortensen

  29. iPSYCH, The Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark

    Esben Agerbo, Marie Bækvad-Hansen, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Jane Hvarregaard Christensen, Jakob Grove, Christine Søholm Hansen, David M Hougaard, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Per Qvist, Wesley Thompson, Yunpeng Wang, Shantel Marie Weinsheimer, Ole Mors, Preben Bo Mortensen, Merete Nordentoft, Thomas Werge & Anders D Børglum

  30. Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia

    Tracy M Air

  31. Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany

    Till F M Andlauer, Elisabeth B Binder & Bertram Müller-Myhsok

  32. Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Till F M Andlauer

  33. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

    Silviu-Alin Bacanu, Tim B Bigdeli, Roseann E Peterson, Brien P. Riley & Kenneth S Kendler

  34. Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark

    Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm & Christine Søholm Hansen

  35. Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands

    Aartjan T F Beekman, Rick Jansen, Yuri Milaneschi, Wouter J Peyrot, Johannes H Smit & Brenda W. J. H Penninx

  36. Virginia Institute for Psychiatric and Behavior Genetics, Richmond, VA, USA

    Tim B Bigdeli

  37. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    Elisabeth B Binder

  38. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Julien Bryois, Erik Pettersson, Alexander Viktorin, Patrik K Magnusson, Nancy L Pedersen & Patrick F Sullivan

  39. Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark

    Henriette N Buttenschøn

  40. iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark

    Henriette N Buttenschøn, Jane Hvarregaard Christensen, Jakob Grove, Per Qvist, Preben Bo Mortensen & Anders D Børglum

  41. Human Genetics, Wellcome Trust Sanger Institute, Cambridge, England

    Na Cai

  42. Statistical Genomics and Systems Genetics, European Bioinformatics Institute (EMBL-EBI), Cambridge, England

    Na Cai

  43. Department of Psychiatry, University Hospital of Lausanne, Prilly, VD, Switzerland

    Enrique Castelao, Giorgio Pistis & Martin Preisig

  44. Social Genetic and Developmental Psychiatry Centre, King’s College London, London, England

    Jonathan R I Coleman, Thalia C Eley, Héléna A Gaspar, David M Howard, Peter McGuffin, Niamh Mullins, Paul F O’Reilly, Margarita Rivera, Cathryn M Lewis & Gerome Breen

  45. Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    Lucía Colodro-Conde, Eske M Derks, Scott D Gordon, Penelope A Lind, Sarah E Medland, Jodie N Painter & Nicholas G Martin

  46. Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia

    Baptiste Couvy-Duchesne

  47. Psychological Medicine, Cardiff University, Cardiff, Wales

    Nick Craddock

  48. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA

    Gregory E Crawford

  49. Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA

    Gregory E Crawford

  50. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland

    Gail Davies, Ian J Deary & Andrew M McIntosh

  51. Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany

    Franziska Degenhardt, Andreas J Forstner, Stefan Herms, Per Hoffmann, Sven Cichon & Markus M Nöthen

  52. Department of Epidemiology, Erasmus MC, Rotterdam, Zuid-Holland, the Netherlands

    Nese Direk, Saira Saeed Mirza & Henning Tiemeier

  53. Department of Psychiatry, School Of Medicine, Dokuz Eylul University, Izmir, Turkey

    Nese Direk

  54. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    Erin C Dunn, Roy H Perlis & Jordan W Smoller

  55. Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA

    Erin C Dunn & Jordan W Smoller

  56. Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA

    Erin C Dunn & Jordan W Smoller

  57. Neuroscience and Mental Health, Cardiff University, Cardiff, Wales

    Valentina Escott-Price

  58. Department of Bioinformatics, University of British Columbia, Vancouver, BC, Canada

    Farnush Farhadi Hassan Kiadeh

  59. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Hilary K Finucane

  60. Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA

    Hilary K Finucane

  61. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany

    Jerome C Foo, Josef Frank, Fabian Streit, Jana Strohmaier, Jens Treutlein, Stephanie H Witt, Marcella Rietschel & Thomas G Schulze

  62. Department of Psychiatry (UPK), University of Basel, Basel, Switzerland

    Andreas J Forstner

  63. Department of Biomedicine, University of Basel, Basel, Switzerland

    Andreas J Forstner, Stefan Herms, Per Hoffmann & Sven Cichon

  64. Centre for Human Genetics, University of Marburg, Marburg, Germany

    Andreas J Forstner

  65. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland

    Michael Gill

  66. Psychiatry & Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA

    Fernando S Goes, Dean F MacKinnon, Francis M Mondimore & J Raymond DePaulo

  67. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark

    Jakob Grove

  68. Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, England

    Lynsey S Hall

  69. Department of Neurology, Danish Headache Centre, Rigshospitalet, Glostrup, Denmark

    Thomas F Hansen

  70. Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark

    Thomas F Hansen, Wesley Thompson, Yunpeng Wang, Shantel Marie Weinsheimer & Thomas Werge

  71. iPSYCH, The Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark

    Thomas F Hansen

  72. Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia

    Ian B Hickie

  73. Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

    Georg Homuth

  74. Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Carsten Horn

  75. Max Planck Institute of Psychiatry, Munich, Germany

    Marcus Ising, Stefan Kloiber & Susanne Lucae

  76. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales

    Ian Jones, Michael J Owen & Michael C O’Donovan

  77. Department of Psychological Medicine, University of Worcester, Worcester, England

    Lisa A Jones

  78. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    Eric Jorgenson, Ling Shen & Catherine Schaefer

  79. Psychiatry & The Behavioral Sciences, University of Southern California, Los Angeles, CA, USA

    James A Knowles

  80. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

    Isaac S Kohane

  81. Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Isaac S Kohane

  82. Informatics Program, Boston Children’s Hospital, Boston, MA, USA

    Isaac S Kohane

  83. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England

    Warren W. Kretzschmar & Yihan Li

  84. Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne, Lausanne, VD, Switzerland

    Zoltán Kutalik

  85. Swiss Institute of Bioinformatics, Lausanne, VD, Switzerland

    Zoltán Kutalik

  86. Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, England

    Donald J MacIntyre

  87. Mental Health, NHS 24, Glasgow, Scotland

    Donald J MacIntyre

  88. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

    Wolfgang Maier

  89. Department of Statistics, University of Oxford, Oxford, England

    Jonathan Marchini

  90. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Patrick McGrath & Myrna M Weissman

  91. School of Psychology and Counseling, Queensland University of Technology, Brisbane, QLD, Australia

    Divya Mehta

  92. Child and Youth Mental Health Service, Children’s Health Queensland Hospital and Health Service, South Brisbane, QLD, Australia

    Christel M Middeldorp

  93. Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia

    Christel M Middeldorp

  94. Estonian Genome Center, University of Tartu, Tartu, Estonia

    Evelin Mihailov, Lili Milani, Tõnu Esko & Andres Metspalu

  95. Medical Genetics, University of British Columbia, Vancouver, BC, Canada

    Sara Mostafavi

  96. Department of Statistics, University of British Columbia, Vancouver, BC, Canada

    Sara Mostafavi & Bernard Ng

  97. DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

    Matthias Nauck

  98. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

    Matthias Nauck

  99. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia

    Dale R Nyholt

  100. Humus, Reykjavik, Iceland

    Hogni Oskarsson

  101. Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    Roseann E Peterson

  102. Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, the Netherlands

    Danielle Posthuma

  103. Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    Danielle Posthuma

  104. Solid Biosciences, Boston, MA, USA

    Jorge A Quiroz

  105. Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, MO, USA

    John P Rice, Andrew C Heath & Pamela A F Madden

  106. Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain

    Margarita Rivera

  107. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Robert Schoevers

  108. Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

    Eva C Schulte

  109. Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Ludwig Maximilian University Munich, Munich, Germany

    Eva C Schulte & Thomas G Schulze

  110. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Jianxin Shi

  111. Behavioral Health Services, Kaiser Permanente Washington, Seattle, WA, USA

    Stanley I Shyn

  112. Faculty of Medicine, Department of Psychiatry, University of Iceland, Reykjavik, Iceland

    Engilbert Sigurdsson

  113. School of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia

    Grant C B Sinnamon

  114. Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland

    Daniel J Smith

  115. deCODE Genetics/Amgen, Reykjavik, Iceland

    Hreinn Stefansson, Stacy Steinberg, Thorgeir E Thorgeirsson & Kari Stefansson

  116. College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales

    Katherine E Tansey

  117. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Nordrhein-Westfalen, Germany

    Henning Teismann, Jürgen Wellmann & Klaus Berger

  118. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

    Alexander Teumer & Henry Völzke

  119. Department of Psychiatry, University of California, San Diego, San Diego, CA, USA

    Wesley Thompson

  120. KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway

    Wesley Thompson & Yunpeng Wang

  121. Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, Scotland

    Pippa A Thomson & David J Porteous

  122. Clinical Neurosciences, University of Cambridge, Cambridge, England

    Matthew Traylor

  123. Internal Medicine, Erasmus MC, Rotterdam, Zuid-Holland, the Netherlands

    Andrés G Uitterlinden

  124. Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Daniel Umbricht

  125. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany

    Sandra Van der Auwera & Hans J Grabe

  126. Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands

    Albert M van Hemert

  127. Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    Bradley T. Webb

  128. Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, USA

    Hualin S Xi

  129. Institute for Molecular Bioscience; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia

    Jian Yang

  130. Department of Psychiatry, University of Münster, Münster, Nordrhein-Westfalen, Germany

    Volker Arolt & Udo Dannlowski

  131. Department of Psychiatry, University of Münster, Münster, Germany

    Bernhard T Baune

  132. Department of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, Australia

    Bernhard T Baune

  133. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia

    Bernhard T Baune

  134. Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland

    Sven Cichon

  135. Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany

    Sven Cichon

  136. Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Amsterdam, the Netherlands

    E. J. C de Geus

  137. Centre for Integrative Biology, Università degli Studi di Trento, Trento, Trentino-Alto Adige, Italy

    Enrico Domenici

  138. Department of Psychiatry and Psychotherapy, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Katharina Domschke

  139. Center for NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Katharina Domschke

  140. Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, USA

    Steven P Hamilton

  141. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland

    Caroline Hayward

  142. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Stefan Kloiber

  143. Centre for Addiction and Mental Health, Toronto, ON, Canada

    Stefan Kloiber

  144. Division of Psychiatry, University College London, London, England

    Glyn Lewis

  145. Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA

    Qingqin S Li

  146. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    Andres Metspalu

  147. Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Germany

    Ole Mors

  148. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    Bertram Müller-Myhsok

  149. University of Liverpool, Liverpool, England

    Bertram Müller-Myhsok

  150. Mental Health Center Copenhagen, Copenhagen Universtity Hospital, Copenhagen, Denmark

    Merete Nordentoft

  151. Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, USA

    Sara A Paciga

  152. Psychiatry, Harvard Medical School, Boston, MA, USA

    Roy H Perlis

  153. Psychiatry, University of Iowa, Iowa City, IA, USA

    James B Potash

  154. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA

    Thomas G Schulze

  155. Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Goettingen, Niedersachsen, Germany

    Thomas G Schulze

  156. Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, USA

    Thomas G Schulze

  157. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Kari Stefansson

  158. Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, Zuid-Holland, the Netherlands

    Henning Tiemeier

  159. Department of Psychiatry, Erasmus MC, Rotterdam, Zuid-Holland, the Netherlands

    Henning Tiemeier

  160. Department of Psychiatry, Dalhousie University, Halifax, NS, Canada

    Rudolf Uher

  161. Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA

    Myrna M Weissman

  162. Department of Clinical Medicine, University of Copenhagen, Copenhagen, DK, Denmark

    Thomas Werge

  163. Department of Medical & Molecular Genetics, King’s College London, London, England

    Cathryn M Lewis

  164. Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA

    Douglas F Levinson

  165. NIHR Maudsley Biomedical Research Centre, King’s College London, London, England

    Gerome Breen

  166. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Patrick F Sullivan

  167. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Patrick F Sullivan

Authors
  1. Jonathan R. I. Coleman
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  2. Wouter J. Peyrot
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  3. Kirstin L. Purves
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Consortia

on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

  • Naomi R Wray
  • , Stephan Ripke
  • , Manuel Mattheisen
  • , Maciej Trzaskowski
  • , Enda M Byrne
  • , Abdel Abdellaoui
  • , Mark J Adams
  • , Esben Agerbo
  • , Tracy M Air
  • , Till F M Andlauer
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  • , Julien Bryois
  • , Henriette N Buttenschøn
  • , Jonas Bybjerg-Grauholm
  • , Na Cai
  • , Enrique Castelao
  • , Jane Hvarregaard Christensen
  • , Toni-Kim Clarke
  • , Jonathan R I Coleman
  • , Lucía Colodro-Conde
  • , Baptiste Couvy-Duchesne
  • , Nick Craddock
  • , Gregory E Crawford
  • , Gail Davies
  • , Ian J Deary
  • , Franziska Degenhardt
  • , Eske M Derks
  • , Nese Direk
  • , Conor V Dolan
  • , Erin C Dunn
  • , Thalia C Eley
  • , Valentina Escott-Price
  • , Farnush Farhadi Hassan Kiadeh
  • , Hilary K Finucane
  • , Jerome C Foo
  • , Andreas J Forstner
  • , Josef Frank
  • , Héléna A Gaspar
  • , Michael Gill
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  • , Scott D Gordon
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  • , Lynsey S Hall
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  • , Stephanie H Witt
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  • , Andrew M McIntosh
  • , Andres Metspalu
  • , Ole Mors
  • , Preben Bo Mortensen
  • , Bertram Müller-Myhsok
  • , Merete Nordentoft
  • , Markus M Nöthen
  • , Michael C O’Donovan
  • , Sara A Paciga
  • , Nancy L Pedersen
  • , Brenda W. J. H Penninx
  • , Roy H Perlis
  • , David J Porteous
  • , James B Potash
  • , Martin Preisig
  • , Marcella Rietschel
  • , Catherine Schaefer
  • , Thomas G Schulze
  • , Jordan W Smoller
  • , Kari Stefansson
  • , Henning Tiemeier
  • , Rudolf Uher
  • , Henry Völzke
  • , Myrna M Weissman
  • , Thomas Werge
  • , Cathryn M Lewis
  • , Douglas F Levinson
  • , Gerome Breen
  • , Anders D Børglum
  •  & Patrick F Sullivan

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Correspondence to Thalia C. Eley or Gerome Breen.

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Coleman, J.R.I., Peyrot, W.J., Purves, K.L. et al. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank. Mol Psychiatry 25, 1430–1446 (2020). https://doi.org/10.1038/s41380-019-0546-6

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