Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

被引：95

作者：

Arnau-Soler, Aleix ^{[1
,2
]}

Macdonald-Dunlop, Erin ^{[3
]}

Adams, Mark J. ^{[4
,18
]}

Clarke, Toni-Kim ^{[4
]}

MacIntyre, Donald J. ^{[4
]}

Milburn, Keith ^{[5
]}

Navrady, Lauren ^{[4
]}

Hayward, Caroline ^{[6
]}

McIntosh, Andrew M. ^{[4
,18
,41
]}

Thomson, Pippa A. ^{[1
,2
,114
]}

Wray, Naomi R. ^{[7
,8
]}

Ripke, Stephan ^{[9
,10
,11
]}

Mattheisen, Manuel ^{[12
,13
,14
,15
]}

Trzaskowski, Maciej ^{[7
]}

Byrne, Enda M. ^{[7
]}

Abdellaoui, Abdel ^{[16
,17
]}

Agerbo, Esben ^{[15
,19
,20
]}

Air, Tracy M. ^{[21
]}

Andlauer, Till F. M. ^{[22
,23
]}

Bacanu, Silviu-Alin ^{[24
]}

Baekvad-Hansen, Marie ^{[15
,25
]}

Beekman, Aartjan T. F. ^{[26
,27
]}

Bigdeli, Tim B. ^{[24
,28
]}

Binder, Elisabeth B. ^{[22
,29
]}

Blackwood, Douglas H. R. ^{[18
]}

Bryois, Julien ^{[30
]}

Buttenscon, Henriette N. ^{[14
,15
,31
]}

Bybjerg-Grauholm, Jonas ^{[15
,25
]}

Cai, Na ^{[32
,33
]}

Castelao, Enrique ^{[34
]}

Christensen, Jane Hvarregaard ^{[13
,14
,15
]}

Coleman, Jonathan R., I ^{[18
]}

Colodro-Conde, Luca ^{[36
]}

Couvy-Duchesne, Baptiste ^{[8
,37
]}

Craddock, Nick ^{[38
]}

Rawford, Gregory E. C. ^{[39
,40
]}

Davies, Gail ^{[41
]}

Deary, Ian J. ^{[41
]}

Degenhardt, Franziska ^{[42
,43
]}

Derks, Eske M. ^{[36
]}

Direk, Nese ^{[44
,45
]}

Dolan, Conor, V ^{[16
,17
]}

Dunn, Erin C. ^{[46
,47
,48
]}

Eley, Thalia C. ^{[35
]}

Escott-Price, Valentina ^{[49
]}

Kiadeh, Farnush Farhadi Hassan ^{[50
]}

Finucane, Hilary K. ^{[51
,52
]}

Foo, Jerome C. ^{[53
]}

Forstner, Andreas J. ^{[42
,43
,54
,55
]}

Frank, Josef ^{[53
]}

机构：

[1] Univ Edinburgh, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh, Midlothian, Scotland

[2] MRC, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

[3] Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Teviot Pl, Edinburgh, Midlothian, Scotland

[4] Univ Edinburgh, Div Psychiat, Deanery Clin Sci, Royal Edinburgh Hosp, Morningside Pk, Edinburgh EH10 5HF, Midlothian, Scotland

[5] Univ Dundee, Hlth Informat Ctr, Dundee, Scotland

[6] Univ Edinburgh, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

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

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

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

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

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

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

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

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

[15] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark

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

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

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

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

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

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

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

[23] Munich Cluster Syst Neurol SyNergy, Munich, Germany

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

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

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

[27] GGZ inGeest, Amsterdam, Netherlands

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

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

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

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

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

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

[34] Univ Hosp Lausanne, Dept Psychiat, Prilly, Vaud, Switzerland

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

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

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

[38] Cardiff Univ, Psychol Med, Cardiff, S Glam, Wales

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

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

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

[42] Univ Bonn, Inst Human Genet, Bonn, Germany

[43] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany

[44] Erasmus MC, Epidemiol, Rotterdam, Zuid Holland, Netherlands

[45] Dokuz Eylul Univ, Sch Med, Psychiat, Izmir, Turkey

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

[47] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit PNGU, Boston, MA 02114 USA

[48] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA

[49] Cardiff Univ, Neurosci & Mental Hlth, Cardiff, S Glam, Wales

[50] Univ British Columbia, Bioinformat, Vancouver, BC, Canada

来源：

TRANSLATIONAL PSYCHIATRY | 2019年 / 9卷 / 1期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

SCOTTISH FAMILY HEALTH; LIFE EVENTS; SEROTONIN TRANSPORTER; MAJOR DEPRESSION; THREATENING EXPERIENCES; GENETIC MODERATION; AFRICAN-AMERICAN; ADOLESCENT TWIN; ASSOCIATION; RISK;

D O I：

10.1038/s41398-018-0360-y

中图分类号：

R749 [精神病学];

学科分类号：

100204 [神经病学];

摘要：

Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 x 10(-6)). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 x 10(-9); total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 x 10(-8); dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 x 10(-8); dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 x 10(-6)). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 x 10(-3)). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.

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