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Association between substance use disorder and polygenic liability to schizophrenia
Hartz, S. M., Horton, A. C., Oehlert, M., Carey, C. E., Agrawal, A., Bogdan, R., Chen, L.-S., Hancock, D. B., Johnson, E. O., Pato, C. N., Pato, M. T., Rice, J. P., & Bierut, L. J. (2017). Association between substance use disorder and polygenic liability to schizophrenia. Biological Psychiatry, 82(10), 709-715. https://doi.org/10.1016/j.biopsych.2017.04.020
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-R-2 range 0.8-3.7%; minimum p = 4 x 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.
