Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder A Mendelian Randomization Study

被引：34

作者：

Polimanti, Renato ^{[1
,2
]}

Ratanatharathorn, Andrew ^{[3
,9
]}

Maihofer, Adam X. ^{[4
,5
,6
,18
]}

Choi, Karmel W. ^{[7
,8
,9
]}

Stein, Murray B. ^{[4
,10
,18
]}

Morey, Rajendra A. ^{[11
,12
,51
]}

Logue, Mark W. ^{[13
,14
,22
]}

Nievergelt, Caroline M. ^{[4
,5
,6
,18
]}

Stein, Dan J. ^{[15
]}

Koenen, Karestan C. ^{[9
,124
]}

Gelernter, Joel ^{[1
,2
,16
,17
,61
]}

Klengel, Torsten ^{[19
]}

Atkinson, Elizabeth G. ^{[7
]}

Chen, Chia-Yen ^{[7
]}

Coleman, Jonathan R. I. ^{[20
]}

Dalvie, Shareefa ^{[15
]}

Duncan, Laramie E. ^{[21
]}

Provost, Allison C. ^{[23
]}

Torres, Katy ^{[18
]}

Aiello, Allison E. ^{[24
]}

Almli, Lynn M. ^{[25
]}

Amstadter, Ananda B. ^{[26
]}

Andersen, Soren B. ^{[27
]}

Andreassen, Ole A. ^{[28
]}

Arbisi, Paul A. ^{[29
]}

Ashley-Koch, Allison E. ^{[11
]}

Austin, S. Bryn ^{[30
]}

Avdibegovic, Esmina ^{[31
]}

Babic, Dragan ^{[32
]}

Baekvad-Hansen, Marie ^{[33
]}

Baker, Dewleen G. ^{[18
]}

Beckham, Jean C. ^{[34
]}

Bierut, Laura J. ^{[35
]}

Bisson, Jonathan I. ^{[36
]}

Boks, Marco P. ^{[37
]}

Bolger, Elizabeth A. ^{[19
]}

Borglum, Anders D. ^{[38
]}

Bradley, Bekh ^{[39
]}

Brashear, Megan ^{[40
,41
]}

Breen, Gerome ^{[42
]}

Bryant, Richard A. ^{[43
]}

Bustamante, Angela C. ^{[44
]}

Bybjerg-Grauholm, Jonas ^{[33
]}

Calabrese, Joseph R. ^{[45
]}

Caldas-de-Almeida, Jose M. ^{[46
]}

Dale, Anders M. ^{[47
]}

Daly, Mark J. ^{[48
]}

Daskalakis, Nikolaos P. ^{[23
]}

Deckert, Juergen ^{[49
]}

Delahanty, Douglas L. ^{[50
]}

机构：

[1] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA

[2] Vet Affairs Connecticut Healthcare Ctr, West Haven, CT USA

[3] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA

[4] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA

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

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

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

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

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

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

[11] Duke Univ, Dept Psychiat, Durham, NC 27706 USA

[12] Durham Vet Affairs Med Ctr, Durham, NC USA

[13] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA

[14] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA

[15] Univ Cape Town, Dept Psychiat, South African Med Res Council, Unit Risk & Resilience Mental Disorders, Cape Town, South Africa

[16] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA

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

[18] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA

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

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

[21] Stanford Univ, Dept Psychiat & Biobehav Sci, Stanford, CA 94305 USA

[22] Natl Ctr PTSD, Vet Affair Boston Healthcare Syst, Boston, MA USA

[23] Cohen Vet Biosci, Cambridge, MA USA

[24] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[25] Carter Consulting, Atlanta, GA USA

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

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

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

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

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

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

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

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

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

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

[36] Cardiff Univ, Natl Ctr Mental Hlth, Ctr Psychiat Genet & Genom, Med Res Council, Cardiff, S Glam, Wales

[37] Univ Med Ctr, Dept Translat Neurosci, Utrecht Brain Ctr Rudolf Magnus, Utrecht, Netherlands

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

[39] Atlanta Vet Affairs Hlth Care Syst, Mental Hlth Serv Line, Decatur, GA USA

[40] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA

[41] Louisiana State Univ, Dept Epidemiol, Hlth Sci Ctr, New Orleans, LA USA

[42] Kings Coll London, Biomed Res Ctr Maudsley, Natl Inst Hlth Res, London, England

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

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

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

[46] Lisbon Inst Global Mental Hlth, Chron Dis Res Ctr CEDOC, Lisbon, Portugal

[47] Univ Calif San Diego, Dept Radiol, Dept Neurosci, San Diego, CA 92103 USA

[48] Massachusetts Gen Hosp, PNGU, Boston, MA 02114 USA

[49] Univ Hosp Wurzburg, Ctr Mental Hlth Psychiat Psychosomat & Psychother, Wurzburg, Germany

[50] Kent State Univ, Dept Psychol Sci, Kent, OH 44242 USA

来源：

JAMA NETWORK OPEN | 2019年 / 2卷 / 05期

基金：

美国国家卫生研究院;

关键词：

COGNITIVE-ABILITY; GENETIC-VARIANTS; RNA-SEQ; RISK; SCHIZOPHRENIA; TRAJECTORIES; DIVERSITY; PTSD;

D O I：

10.1001/jamanetworkopen.2019.3447

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IMPORTANCE There is a well-established negative association of educational attainment (EA) and other traits related to cognitive ability with posttraumatic stress disorder (PTSD), but the underlying mechanisms are poorly understood. OBJECTIVES To investigate the association of PTSD with traits related to EA. DESIGN, SETTING, AND PARTICIPANTS Genetic correlation, polygenic risk scoring, and mendelian randomization (MR) were conducted including 23 185 individuals with PTSD and 151 309 control participants from the Psychiatric Genomics Consortium for PTSD and up to 1 131 881 individuals assessed for EA and related traits from UK Biobank, 23andMe, and the Social Science Genetic Association Consortium. Data were analyzed from July 3 through November 19, 2018. MAIN OUTCOMES AND MEASURES Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. RESULTS Summary association data from multiple genome-wide association studies were available for a total of 1 180 352 participants (634 391 [53.7%] women). Posttraumatic stress disorder showed negative genetic correlations with EA (r(g) = -0.26; SE = 0.05; P = 4.60 x 10(-8)). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (beta = -0.23; 95% CI, -0.07 to -0.39; P = .004). Investigating potential mediators of the EA-PTSD association, propensity for trauma exposure and risk-taking behaviors were observed as risk factors for PTSD independent of EA (trauma exposure: beta = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 x 10(-5); risk-taking: beta = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 x 10(-4)), while income may mediate the association of EA with PSTD (MR income: beta = -0.18; 95% CI, -0.29 to -0.07; P =.001; MR EA: beta = -0.23; 95% CI, -0.39 to -0.07; P =.004; multivariable MR income: beta = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: beta = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79). CONCLUSIONS AND RELEVANCE Large-scale genomic data sets add further evidence to the negative association of EA with PTSD, also supporting the role of economic status as a mediator in the association observed.

引用

页数：17

共 59 条

[1]

Abdellaoui A., 2018, BIORXIV, DOI [10.1101/457515, DOI 10.1101/457515]

[2] Genetic effects on gene expression across human tissues [J].

Aguet, Francois ;

Brown, Andrew A. ;

Castel, Stephane E. ;

Davis, Joe R. ;

He, Yuan ;

Jo, Brian ;

Mohammadi, Pejman ;

Park, Yoson ;

Parsana, Princy ;

Segre, Ayellet V. ;

Strober, Benjamin J. ;

Zappala, Zachary ;

Cummings, Beryl B. ;

Gelfand, Ellen T. ;

Hadley, Kane ;

Huang, Katherine H. ;

Lek, Monkol ;

Li, Xiao ;

Nedzel, Jared L. ;

Nguyen, Duyen Y. ;

Noble, Michael S. ;

Sullivan, Timothy J. ;

Tukiainen, Taru ;

MacArthur, Daniel G. ;

Getz, Gad ;

Management, Nih Program ;

Addington, Anjene ;

Guan, Ping ;

Koester, Susan ;

Little, A. Roger ;

Lockhart, Nicole C. ;

Moore, Helen M. ;

Rao, Abhi ;

Struewing, Jeffery P. ;

Volpi, Simona ;

Collection, Biospecimen ;

Brigham, Lori E. ;

Hasz, Richard ;

Hunter, Marcus ;

Johns, Christopher ;

Johnson, Mark ;

Kopen, Gene ;

Leinweber, William F. ;

Lonsdale, John T. ;

McDonald, Alisa ;

Mestichelli, Bernadette ;

Myer, Kevin ;

Roe, Bryan ;

Salvatore, Michael ;

Shad, Saboor .

NATURE, 2017, 550 (7675) :204-+

[3] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[4] Analysis of shared heritability in common disorders of the brain [J].

Anttila, Verneri ;

Bulik-Sullivan, Brendan ;

Finucane, Hilary K. ;

Walters, Raymond K. ;

Bras, Jose ;

Duncan, Laramie ;

Escott-Price, Valentina ;

Falcone, Guido J. ;

Gormley, Padhraig ;

Malik, Rainer ;

Patsopoulos, Nikolaos A. ;

Ripke, Stephan ;

Wei, Zhi ;

Yu, Dongmei ;

Lee, Phil H. ;

Turley, Patrick ;

Grenier-Boley, Benjamin ;

Chouraki, Vincent ;

Kamatani, Yoichiro ;

Berr, Claudine ;

Letenneur, Luc ;

Hannequin, Didier ;

Amouyel, Philippe ;

Boland, Anne ;

Deleuze, Jean-Francois ;

Duron, Emmanuelle ;

Vardarajan, Badri N. ;

Reitz, Christiane ;

Goate, Alison M. ;

Huentelman, Matthew J. ;

Kamboh, M. Ilyas ;

Larson, Eric B. ;

Rogaeva, Ekaterina ;

St George-Hyslop, Peter ;

Hakonarson, Hakon ;

Kukull, Walter A. ;

Farrer, Lindsay A. ;

Barnes, Lisa L. ;

Beach, Thomas G. ;

Demirci, F. Yesim ;

Head, Elizabeth ;

Hulette, Christine M. ;

Jicha, Gregory A. ;

Kauwe, John S. K. ;

Kaye, Jeffrey A. ;

Leverenz, James B. ;

Levey, Allan I. ;

Lieberman, Andrew P. ;

Pankratz, Vernon S. ;

Poon, Wayne W. .

SCIENCE, 2018, 360 (6395) :1313-+

[5] Comparing Trauma Exposure, Mental Health Needs, and Service Utilization Across Clinical Samples of Refugee, Immigrant, and US-Origin Children [J].

Betancourt, Theresa S. ;

Newnham, Elizabeth A. ;

Birman, Dina ;

Lee, Robert ;

Ellis, B. Heidi ;

Layne, Christopher M. .

JOURNAL OF TRAUMATIC STRESS, 2017, 30 (03) :209-218

[6] Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator [J].

Bowden, Jack ;

Smith, George Davey ;

Haycock, Philip C. ;

Burgess, Stephen .

GENETIC EPIDEMIOLOGY, 2016, 40 (04) :304-314

[7] Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression [J].

Bowden, Jack ;

Smith, George Davey ;

Burgess, Stephen .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2015, 44 (02) :512-525

[8]

Bowling A, 2005, HDB HLTH RES METHODS

[9] An atlas of genetic correlations across human diseases and traits [J].

Bulik-Sullivan, Brendan ;

Finucane, Hilary K. ;

Anttila, Verneri ;

Gusev, Alexander ;

Day, Felix R. ;

Loh, Po-Ru ;

Duncan, Laramie ;

Perry, John R. B. ;

Patterson, Nick ;

Robinson, Elise B. ;

Daly, Mark J. ;

Price, Alkes L. ;

Neale, Benjamin M. .

NATURE GENETICS, 2015, 47 (11) :1236-+

[10]

Burgess S, 2015, AM J EPIDEMIOL, V181, P251, DOI 10.1093/aje/kwu283

← 1 2 3 4 5 6 →