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Biol Psychiatry. 2017 Nov 15;82(10):709-715. doi: 10.1016/j.biopsych.2017.04.020. Epub 2017 Jun 6.

Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia.

Author information

1
Washington University in St. Louis, St. Louis, Missouri. Electronic address: hartzs@wustl.edu.
2
Washington University in St. Louis, St. Louis, Missouri.
3
Veterans Affairs Eastern Kansas Health Care System, Leavenworth, Kansas; The University of Kansas Medical Center, Kansas City, Kansas.
4
RTI International, Research Triangle Park, North Carolina.
5
State University of New York Downstate Medical Center, Brooklyn, New York.

Abstract

BACKGROUND:

There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity.

METHODS:

We tested the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: the Collaborative Genetic Study of Nicotine Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317 control subjects). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to the 1000 Genomes reference panel.

RESULTS:

In each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo-R2 range 0.8-3.7%; minimum p = 4 × 10-23).

CONCLUSIONS:

These results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder.

KEYWORDS:

Genetics; Polygenic risk score; Schizophrenia; Substance dependence; Substance use disorder

PMID:
28739213
PMCID:
PMC5643224
DOI:
10.1016/j.biopsych.2017.04.020
[Indexed for MEDLINE]
Free PMC Article

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