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

被引：111

作者：

Coleman, Jonathan R. I. ^{[1
,2
,43
]}

Peyrot, Wouter J. ^{[3
,33
,34
]}

Purves, Kirstin L. ^{[1
]}

Davis, Katrina A. S. ^{[2
,4
]}

Rayner, Christopher ^{[1
]}

Choi, Shing Wan ^{[1
]}

Hubel, Christopher ^{[1
,2
]}

Gaspar, Helena A. ^{[1
,2
,43
]}

Kan, Carol ^{[4
]}

Van der Auwera, Sandra ^{[5
]}

Adams, Mark James ^{[6
]}

Lyall, Donald M. ^{[7
]}

Choi, Karmel W. ^{[8
,9
,10
,11
]}

Dunn, Erin C. ^{[8
,10
,11
,12
,54
,55
]}

Vassos, Evangelos ^{[1
,2
]}

Danese, Andrea ^{[1
,13
,14
]}

Maughan, Barbara ^{[1
]}

Grabe, Hans J. ^{[5
]}

Lewis, Cathryn M. ^{[1
,2
,43
,157
]}

O'Reilly, Paul F. ^{[1
,43
]}

McIntosh, Andrew M. ^{[6
,49
]}

Smith, Daniel J. ^{[7
]}

Wray, Naomi R. ^{[15
,16
]}

Hotopf, Matthew ^{[2
,4
]}

Eley, Thalia C. ^{[1
,2
,43
]}

Breen, Gerome ^{[1
,2
,43
,159
]}

Wray, Naomi R. ^{[15
,16
]}

Ripke, Stephan ^{[17
,18
,19
]}

Mattheisen, Manuel ^{[20
,21
,22
]}

Trzaskowski, Maciej ^{[15
]}

Byrne, Enda M. ^{[15
]}

Abdellaoui, Abdel ^{[23
,24
]}

Adams, Mark J. ^{[6
]}

Agerbo, Esben ^{[25
,26
,27
]}

Air, Tracy M. ^{[28
]}

Andlauer, Till F. M. ^{[29
,30
]}

Bacanu, Silviu-Alin ^{[31
]}

Baekvad-Hansen, Marie ^{[27
,32
]}

Beekman, Aartjan T. F. ^{[33
,34
]}

Bigdeli, Tim B. ^{[31
,35
]}

Binder, Elisabeth B. ^{[29
,36
]}

Bryois, Julien ^{[37
]}

Buttenschon, Henriette N. ^{[27
,38
,39
]}

Bybjerg-Grauholm, Jonas ^{[27
,32
]}

Cai, Na ^{[40
,41
]}

Castelao, Enrique ^{[42
]}

Christensen, Jane Hvarregaard ^{[22
,27
,39
]}

Clarke, Toni-Kim ^{[6
]}

Coleman, Jonathan R. I. ^{[1
,2
,43
]}

Colodro-Conde, Lucia ^{[44
]}

机构：

[1] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London, England

[2] South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr, London, England

[3] Vrije Univ Med Ctr, Dept Psychiat, Amsterdam UMC, Amsterdam, Netherlands

[4] Kings Coll London, Dept Psychol Med, Inst Psychiat Psychol & Neurosci, London, England

[5] Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany

[6] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland

[7] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland

[8] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[9] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[10] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[11] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Genom Med, Boston, MA 02114 USA

[12] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA

[13] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat Psychol & Neurosci, London, England

[14] South London & Maudsley NHS Fdn Trust, Natl & Specialist CAMHS Trauma & Anxiety Clin, London, England

[15] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[16] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[17] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[18] Univ Med Berlin, Dept Psychiat & Psychotherapy, Campus Charite Mitte, Berlin, Germany

[19] Broad Inst, Med & Populat Genet, Cambridge, MA USA

[20] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany

[21] Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden

[22] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[23] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[24] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands

[25] Aarhus Univ, Ctr Integrated Register Based Res, Aarhus, Denmark

[26] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark

[27] Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark

[28] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia

[29] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany

[30] Tech Univ Munich, Dept Neurol, Klinikum Rechts Isar, Munich, Germany

[31] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA

[32] Statens Serum Inst, Dept Congenital Disorders, Ctr Neonatal Screening, Copenhagen, Denmark

[33] Vrije Univ Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[34] GGZ inGeest, Amsterdam, Netherlands

[35] Virginia Inst Psychiat & Behav Genet, Richmond, VA USA

[36] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

[37] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[38] Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, Aarhus, Denmark

[39] Aarhus Univ, Ctr Integrat Sequencing, iSEQ, Aarhus, Denmark

[40] Wellcome Trust Sanger Inst, Human Genet, Cambridge, England

[41] European Bioinformat Inst EMBL EBI, Stat Genom & Syst Genet, Cambridge, England

[42] Univ Hosp Lausanne, Dept Psychiat, Prilly, VD, Switzerland

[43] Kings Coll London, Social Genet & Dev Psychiat Ctr, London, England

[44] QIMR Berghofer Med Res Inst, Genet & Computat Biol, Brisbane, Qld, Australia

[45] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia

[46] Cardiff Univ, Psychol Med, Cardiff, Wales

[47] Duke Univ, Ctr Genom & Computat Biol, Durham, NC USA

[48] Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27706 USA

[49] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[50] Univ Bonn, Inst Human Genet, Sch Med, Bonn, Germany

来源：

MOLECULAR PSYCHIATRY | 2020年 / 25卷 / 07期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

CHILDHOOD MALTREATMENT; PSYCHIATRIC-DISORDERS; ASSOCIATION ANALYSIS; BIOLOGICAL INSIGHTS; MENTAL-HEALTH; EVENTS; RISK; SYMPTOMS; HERITABILITY; ADVERSITY;

D O I：

10.1038/s41380-019-0546-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (r(g) = 0.24, p = 1.8 x 10(-7) versus r(g) = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 x 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.

引用

页码：1430 / 1446

页数：17

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