TY - JOUR
T1 - Psychosocial moderation of polygenic risk for cannabis involvement
T2 - the role of trauma exposure and frequency of religious service attendance
AU - Meyers, Jacquelyn L.
AU - Salvatore, Jessica E.
AU - Aliev, Fazil
AU - Johnson, Emma C.
AU - McCutcheon, Vivia V.
AU - Su, Jinni
AU - Kuo, Sally I.Chun
AU - Lai, Dongbing
AU - Wetherill, Leah
AU - Wang, Jen C.
AU - Chan, Grace
AU - Hesselbrock, Victor
AU - Foroud, Tatiana
AU - Bucholz, Kathleen K.
AU - Edenberg, Howard J.
AU - Dick, Danielle M.
AU - Porjesz, Bernice
AU - Agrawal, Arpana
N1 - Funding Information:
This research was supported by K01DA037914 (to J.L.M.), K02DA32573 and DA040716 (to A.A.), MH109532 and DA040411 (to E.J.), K01AA024152 (to J.E.S.), and K02AA018755 (to D.M.D.). COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut, includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks); Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA (L. Almasy), Virginia Commonwealth University (D. Dick), Icahn School of Medicine at Mount Sinai (A. Goate), and Howard University (R. Taylor). Other COGA collaborators include: L. Bauer (University of Connecticut); J. McClintick, L. Wetherill, X. Xuei, Y. Liu, D. Lai, S. O’Connor, M. Plawecki, S. Lourens (Indiana University); G. Chan (University of Iowa; University of Connecticut); J. Meyers, D. Chorlian, C. Kamarajan, A. Pandey, J. Zhang (SUNY Downstate); J.-C. Wang, M. Kapoor, S. Bertelsen (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); J. Salvatore, F. Aliev, B. Cho (Virginia Commonwealth University); and Mark Kos (University of Texas Rio Grande Valley). A. Parsian and H. Chen are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Cannabis use and disorders (CUD) are influenced by multiple genetic variants of small effect and by the psychosocial environment. However, this information has not been effectively incorporated into studies of gene–environment interaction (GxE). Polygenic risk scores (PRS) that aggregate the effects of genetic variants can aid in identifying the links between genetic risk and psychosocial factors. Using data from the Pasman et al. GWAS of cannabis use (meta-analysis of data from the International Cannabis Consortium and UK Biobank), we constructed PRS in the Collaborative Study on the Genetics of Alcoholism (COGA) participants of European (N: 7591) and African (N: 3359) ancestry. The primary analyses included only individuals of European ancestry, reflecting the ancestral composition of the discovery GWAS from which the PRS was derived. Secondary analyses included the African ancestry sample. Associations of PRS with cannabis use and DSM-5 CUD symptom count (CUDsx) and interactions with trauma exposure and frequency of religious service attendance were examined. Models were adjusted for sex, birth cohort, genotype array, and ancestry. Robustness models were adjusted for cross-term interactions. Higher PRS were associated with a greater likelihood of cannabis use and with CUDsx among participants of European ancestry (p < 0.05 and p < 0.1 thresholds, respectively). PRS only influenced cannabis use among those exposed to trauma (R2: 0.011 among the trauma exposed vs. R2: 0.002 in unexposed). PRS less consistently influenced cannabis use among those who attend religious services less frequently; PRS × religious service attendance effects were attenuated when cross-term interactions with ancestry and sex were included in the model. Polygenic liability to cannabis use was related to cannabis use and, less robustly, progression to symptoms of CUD. This study provides the first evidence of PRS × trauma for cannabis use and demonstrates that ignoring important aspects of the psychosocial environment may mask genetic influences on polygenic traits.
AB - Cannabis use and disorders (CUD) are influenced by multiple genetic variants of small effect and by the psychosocial environment. However, this information has not been effectively incorporated into studies of gene–environment interaction (GxE). Polygenic risk scores (PRS) that aggregate the effects of genetic variants can aid in identifying the links between genetic risk and psychosocial factors. Using data from the Pasman et al. GWAS of cannabis use (meta-analysis of data from the International Cannabis Consortium and UK Biobank), we constructed PRS in the Collaborative Study on the Genetics of Alcoholism (COGA) participants of European (N: 7591) and African (N: 3359) ancestry. The primary analyses included only individuals of European ancestry, reflecting the ancestral composition of the discovery GWAS from which the PRS was derived. Secondary analyses included the African ancestry sample. Associations of PRS with cannabis use and DSM-5 CUD symptom count (CUDsx) and interactions with trauma exposure and frequency of religious service attendance were examined. Models were adjusted for sex, birth cohort, genotype array, and ancestry. Robustness models were adjusted for cross-term interactions. Higher PRS were associated with a greater likelihood of cannabis use and with CUDsx among participants of European ancestry (p < 0.05 and p < 0.1 thresholds, respectively). PRS only influenced cannabis use among those exposed to trauma (R2: 0.011 among the trauma exposed vs. R2: 0.002 in unexposed). PRS less consistently influenced cannabis use among those who attend religious services less frequently; PRS × religious service attendance effects were attenuated when cross-term interactions with ancestry and sex were included in the model. Polygenic liability to cannabis use was related to cannabis use and, less robustly, progression to symptoms of CUD. This study provides the first evidence of PRS × trauma for cannabis use and demonstrates that ignoring important aspects of the psychosocial environment may mask genetic influences on polygenic traits.
UR - http://www.scopus.com/inward/record.url?scp=85073656513&partnerID=8YFLogxK
U2 - 10.1038/s41398-019-0598-z
DO - 10.1038/s41398-019-0598-z
M3 - Article
C2 - 31636251
AN - SCOPUS:85073656513
VL - 9
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 269
ER -