International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

被引：378

作者：

Nievergelt, Caroline M. ^{[1
,2
,3
]}

Maihofer, Adam X. ^{[1
,2
,3
]}

Klengel, Torsten ^{[4
,5
,6
]}

Atkinson, Elizabeth G. ^{[7
,8
]}

Chen, Chia-Yen ^{[7
,8
,9
]}

Choi, Karmel W. ^{[7
,10
,11
]}

Coleman, Jonathan R., I ^{[12
,13
]}

Dalvie, Shareefa ^{[14
]}

Duncan, Laramie E. ^{[15
]}

Gelernter, Joel ^{[16
,17
,18
]}

Levey, Daniel F. ^{[18
,19
]}

Logue, Mark W. ^{[20
]}

Polimanti, Renato ^{[18
,19
]}

Provost, Allison C. ^{[21
]}

Ratanatharathorn, Andrew ^{[11
]}

Stein, Murray B. ^{[1
,22
,23
]}

Torres, Katy ^{[1
,2
,3
]}

Aiello, Allison E. ^{[24
]}

Almli, Lynn M. ^{[25
]}

Amstadter, Ananda B. ^{[26
]}

Andersen, Sren B. ^{[27
]}

Andreassen, Ole A. ^{[28
]}

Arbisi, Paul A. ^{[29
]}

Ashley-Koch, Allison E. ^{[30
]}

Austin, S. Bryn ^{[4
,31
,32
,33
]}

Avdibegovic, Esmina ^{[34
]}

Babic, Dragan ^{[35
]}

Baekvad-Hansen, Marie ^{[36
,37
]}

Baker, Dewleen G. ^{[1
,2
,23
]}

Beckham, Jean C. ^{[38
,39
,40
]}

Bierut, Laura J. ^{[41
]}

Bisson, Jonathan, I ^{[42
]}

Boks, Marco P. ^{[43
]}

Bolger, Elizabeth A. ^{[4
,5
]}

Brglum, Anders D. ^{[37
,44
,45
]}

Bradley, Bekh ^{[25
,46
]}

Brashear, Megan ^{[47
]}

Breen, Gerome ^{[12
,13
]}

Bryant, Richard A. ^{[48
]}

Bustamante, Angela C. ^{[49
]}

Bybjerg-Grauholm, Jonas ^{[36
,37
]}

Calabrese, Joseph R. ^{[50
]}

Caldas-de-Almeida, Jose M. ^{[51
]}

Dale, Anders M. ^{[52
]}

Daly, Mark J. ^{[9
]}

Daskalakis, Nikolaos P. ^{[4
,5
,21
,53
]}

Deckert, Juergen ^{[54
]}

Delahanty, Douglas L. ^{[55
,56
]}

Dennis, Michelle F. ^{[38
,39
,40
]}

Disner, Seth G. ^{[57
]}

机构：

[1] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[2] Vet Affairs San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA 92093 USA

[3] Vet Affairs San Diego Healthcare Syst, Res Serv, San Diego, CA 92093 USA

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

[5] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA

[6] Univ Med Ctr Goettingen, Dept Psychiat, Gottingen, Germany

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

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

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

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

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

[12] Kings Coll London, Genet & Dev Psychiat Ctr, Inst Psychiat, London, England

[13] Kings Coll London, NIHR BRC Maudsley, London, England

[14] Univ Cape Town, Dept Psychiat, SA MRC Unit Risk & Resilience Mental Disorders, Cape Town, South Africa

[15] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[16] US Dept Vet Affairs, Dept Psychiat, West Haven, CT USA

[17] Yale Univ, Sch Med, Dept Genet & Neurosci, New Haven, CT USA

[18] VA Connecticut Healthcare Ctr, West Haven, CT USA

[19] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA

[20] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA

[21] Cohen Vet Biosci, Cambridge, MA USA

[22] Vet Affairs San Diego Healthcare Syst, Mill Vet Program, San Diego, CA USA

[23] Vet Affairs San Diego Healthcare Syst, Psychiat Serv, San Diego, CA USA

[24] Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA

[25] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

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

[27] Danish Vet Ctr, Res & Knowledge Ctr, Ringsted, Sjaelland, Denmark

[28] Univ Oslo, Inst Clin Med, Oslo, Norway

[29] Minneapolis VA Hlth Care Syst, Mental Hlth Serv Line, Minneapolis, MN USA

[30] Duke Univ, Duke Mol Physiol Inst, Durham, NC USA

[31] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA USA

[32] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[33] Harvard Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA

[34] Univ Clin Ctr Tuzla, Dept Psychiat, Tuzla, Bosnia & Herceg

[35] Univ Clin Ctr Mostar, Dept Psychiat, Mostar, Bosnia & Herceg

[36] Statens Serum Inst, Dept Congenital Disorders, Copenhagen, Denmark

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

[38] Durham VA Med Ctr, Durham, NC USA

[39] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA

[40] VA Mid Atlantic Mental Illness Res Educ & Clin Ct, Genet Res Lab, Durham, NC USA

[41] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[42] Cardiff Univ, Natl Ctr Mental Hlth, MRC Ctr Psychiat Genet & Genom, Cardiff, S Glam, Wales

[43] UMC Utrecht Brain Ctr Rudolf Magnus, Dept Translat Neurosci, Utrecht, Netherlands

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

[45] Aarhus Univ, Dept Biomed Human Genet, Aarhus, Denmark

[46] Atlanta VA Hlth Care Syst, Mental Hlth Serv Line, Decatur, GA USA

[47] Louisiana State Univ, Sch Publ Hlth & Dept Epidemiol, Hlth Sci Ctr, New Orleans, LA USA

[48] Univ New South Wales, Dept Psychol, Sydney, NSW, Australia

[49] Univ Michigan, Dept Internal Med, Med Sch, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA

[50] Univ Hosp, Dept Psychiat, Cleveland, OH USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

POSTTRAUMATIC-STRESS-DISORDER; HUMAN DEMOGRAPHIC HISTORY; LD SCORE REGRESSION; PARKINSON DISEASE; SNP HERITABILITY; TRAUMA; EFFICIENT; PREVENTION; PROFILES; SYMPTOMS;

D O I：

10.1038/s41467-019-12576-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

引用

页数：16

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