Association between substance use disorder and polygenic liability to schizophrenia

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 Here, we test the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schiz...

Full description

Saved in:
Bibliographic Details
Published in:Biological psychiatry (1969) 2017-11, Vol.82 (10), p.709-715
Main Authors: Hartz, Sarah M., MD PhD, Horton, Amy, PhD, Oehlert, Mary, PhD, Carey, Caitlin E., MA, Agrawal, Arpana, PhD, Bogdan, Ryan, PhD, Chen, Li-Shiun, MD MSc, Hancock, Dana B., PhD, Johnson, Eric O., PhD, Pato, Carlos, MD, Pato, Michele, MD, Rice, John P., PhD, Bierut, Laura J., MD
Format: Article
Language:English
Subjects:
Adult
Case-Control Studies
Comorbidity
Female
Genetic Predisposition to Disease - genetics
Genetics
Genome-Wide Association Study
Genotype
Humans
Male
Meta-Analysis as Topic
Middle Aged
Multifactorial Inheritance - genetics
Phenotype
Polygenic risk score
Polymorphism, Single Nucleotide - genetics
Psychiatry
Risk Factors
Schizophrenia
Schizophrenia - genetics
Substance dependence
Substance use disorder
Substance-Related Disorders - genetics
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Here, we test 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: COGEND (ascertained for nicotine dependence n=918 cases, 988 controls), COGA (ascertained for alcohol dependence n=643 cases, 384 controls), and FSCD (ascertained for cocaine dependence n=210 cases, 317 controls). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to 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=4x10-23 ). 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.
ISSN:0006-3223
1873-2402
1873-2402
DOI:10.1016/j.biopsych.2017.04.020