TY - JOUR
T1 - Genomic risk for post-traumatic stress disorder in families densely affected with alcohol use disorders
AU - Saenz de Viteri, Stacey
AU - Zhang, Jian
AU - Johnson, Emma C.
AU - Barr, Peter B.
AU - Edenberg, Howard J.
AU - Hesselbrock, Victor M.
AU - Nurnberger, John I.
AU - Pandey, Ashwini K.
AU - Kamarajan, Chella
AU - Kinreich, Sivan
AU - Tischfield, Jay A.
AU - Plawecki, Martin H.
AU - Kramer, John R.
AU - Lai, Dongbing
AU - Kuperman, Samuel
AU - Chan, Grace
AU - McCutcheon, Vivia V.
AU - Bucholz, Kathleen K.
AU - Porjesz, Bernice
AU - Meyers, Jacquelyn L.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/8
Y1 - 2023/8
N2 - Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N = 3533) and Million Veterans Program GWAS of PTSD (N = 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD (B = 0.126, p < 0.001), alcohol dependence (B = 0.231, p < 0.001), and cocaine dependence (B = 0.086, p < 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD (B = 0.090, p < 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.
AB - Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N = 3533) and Million Veterans Program GWAS of PTSD (N = 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD (B = 0.126, p < 0.001), alcohol dependence (B = 0.231, p < 0.001), and cocaine dependence (B = 0.086, p < 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD (B = 0.090, p < 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.
UR - http://www.scopus.com/inward/record.url?scp=85163037381&partnerID=8YFLogxK
U2 - 10.1038/s41380-023-02117-9
DO - 10.1038/s41380-023-02117-9
M3 - Article
C2 - 37344610
AN - SCOPUS:85163037381
SN - 1359-4184
VL - 28
SP - 3391
EP - 3396
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 8
ER -