Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31050786
TITLE
Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study.
ABSTRACT
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
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. To investigate the association of PTSD with traits related to EA.
Design, Setting, and Participants
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. To investigate the association of PTSD with traits related to EA. 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
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. To investigate the association of PTSD with traits related to EA. 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. Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR.
Results
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. To investigate the association of PTSD with traits related to EA. 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. Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. 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 (rg = -0.26; SE = 0.05; P = 4.60 × 10-8). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (β = -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: β = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 × 10-5; risk-taking: β = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 × 10-4), while income may mediate the association of EA with PSTD (MR income: β = -0.18; 95% CI, -0.29 to -0.07; P = .001; MR EA: β = -0.23; 95% CI, -0.39 to -0.07; P = .004; multivariable MR income: β = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: β = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79).
Conclusions and Relevance
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. To investigate the association of PTSD with traits related to EA. 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. Genetic correlation obtained from linkage disequilibrium score regression, phenotypic variance explained by polygenic risk scores, and association estimates from MR. 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 (rg = -0.26; SE = 0.05; P = 4.60 × 10-8). Mendelian randomization analysis, conducting considering a random-effects inverse-variance weighted method, indicated that EA has a negative association with PTSD (β = -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: β = 0.37; 95% CI, 0.19 to 0.52; P = 2.57 × 10-5; risk-taking: β = 0.76; 95% CI, 0.38 to 1.13; P = 1.13 × 10-4), while income may mediate the association of EA with PSTD (MR income: β = -0.18; 95% CI, -0.29 to -0.07; P = .001; MR EA: β = -0.23; 95% CI, -0.39 to -0.07; P = .004; multivariable MR income: β = -0.32; 95% CI, -0.57 to 0.07; P = .02; multivariable MR EA: β = -0.04; 95% CI, -0.29 to 0.21; SE, 0.13; P = .79). 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.
DATE PUBLISHED
2019 05 03
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2019/05/04 06:00
pubmed 2019/05/06 06:00
medline 2020/02/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Polimanti R Polimanti Renato R Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut.
Ratanatharathorn A Ratanatharathorn Andrew A Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Maihofer AX Maihofer Adam X AX Veterans Affairs Center of Excellence for Stress and Mental Health and Research Service, Veterans Affairs San Diego Healthcare System, San Diego, California.
Choi KW Choi Karmel W KW Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
Stein MB Stein Murray B MB Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, California.
Morey RA Morey Rajendra A RA Durham Veterans Affairs Medical Center, Durham, North Carolina.
Logue MW Logue Mark W MW Department of Psychiatry, School of Medicine, Boston University, Boston, Massachusetts.
Nievergelt CM Nievergelt Caroline M CM Veterans Affairs Center of Excellence for Stress and Mental Health and Research Service, Veterans Affairs San Diego Healthcare System, San Diego, California.
Stein DJ Stein Dan J DJ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
Koenen KC Koenen Karestan C KC Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
Gelernter J Gelernter Joel J Department of Neuroscience, School of Medicine, Yale University, New Haven, Connecticut.
Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group
INVESTIGATORS
JOURNAL
VOLUME: 2
ISSUE: 5
TITLE: JAMA network open
ISOABBREVIATION: JAMA Netw Open
YEAR: 2019
MONTH: 05
DAY: 03
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2574-3805
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: JAMA Netw Open
COUNTRY: United States
ISSNLINKING: 2574-3805
NLMUNIQUEID: 101729235
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
R01 MH106595 NIMH NIH HHS United States
U01 MH109536 NIMH NIH HHS United States
U01 MH109532 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Cognition physiology
Cross-Sectional Studies physiology
Economic Status physiology
Educational Status physiology
Humans physiology
Mendelian Randomization Analysis methods
Polymorphism, Single Nucleotide methods
Risk-Taking methods
Stress Disorders, Post-Traumatic psychology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's