Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia

作者：Hartz Sarah M^*; Horton Amy C; Oehlert Mary; Carey Caitlin E; Agrawal Arpana; Bogdan Ryan; Chen Li Shiun; Hancock Dana B; Johnson Eric O; Pato Carlos N; Pato Michele T; Rice John P; Bierut Laura J

来源：Biological Psychiatry, 2017, 82(10): 709-715.

DOI：10.1016/j.biopsych.2017.04.020

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

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.

• 出版日期2017-11-15