Journal
FRONTIERS IN GENETICS
Volume 7, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2016.00149
Keywords
substance; polygenic; comorbidity; schizophrenia; depression; cannabis; cocaine
Categories
Funding
- National Science Foundation [DGE-1143954]
- National Institute on Drug Abuse [DA23668, DA32573, DA036583, DA032680]
- Klingenstein Third Generation Foundation
- National Institute on Aging [AG045231]
- Study of Addiction: Genetics and Environment (SAGE) through the NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422, phs000092.v1.p1]
- Gene Environment Association Studies (GENEVA) under GEI
- GENEVA Coordinating Center [U01 HG004446]
- National Center for Biotechnology Information
- Collaborative Study on the Genetics of Alcoholism [COGA] [U10 AA008401]
- Collaborative Genetic Study of Nicotine Dependence [COGEND] [P01 CA089392]
- Family Study of Cocaine Dependence [BCD] [R01 DA013423, R01 DA019963]
- Johns Hopkins University Center for Inherited Disease Research (CIDR)
- NIH GEI [U01HG004438]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH [HHSN268200782096C, U10AA008401]
- National institute on Alcohol Abuse and Alcoholism (NIAAA)
- National Institute on Drug Abuse (NIDA)
- NCI Cancer Center [P30 CA91842]
- Siteman Cancer Center
- ICTS/CTSA [UL1RR024992]
- National Center for Research Resources (NCRR), National Institutes of Health (NIH)
- NIH Roadmap for Medical Research
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Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium's Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)-and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p < 0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: (A) MDD PRS and non-problem cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.
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