Abstract

BACKGROUND: Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders. METHODS: We constructed polygenic risk scores (PRSs) using GWAS meta-analysis summary statistics from a large discovery sample, GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN), for smoking initiation (SI; N?=?631,564), age of initiating regular smoking (AI; N?=?258,251), cigarettes per day (CPD; N?=?258,999), smoking cessation (SC; N?=?312,273), and drinks per week (DPW; N?=?527,402). We then estimated the fixed effect of these PRSs on the liability to 15 phenotypes related to tobacco and alcohol use, substance use disorders, and psychiatric disorders in an independent target sample of Australian adults. RESULTS: : 3.39 %-6.26 %) positively associated with only DPW. The variation of DPW was significantly influenced by sex*PRS-SI, sex*PRS-AI and sex*PRS-DPW. Such interaction effect was not detected in the other 14 phenotypes. CONCLUSIONS: Polygenic risks associated with tobacco use are also associated with liability to alcohol consumption, nicotine dependence, and conduct disorder.

Authors	Chang, Lun-Hsien; Whitfield, John B; Liu, Mengzhen; Medland, Sarah E; Hickie, Ian B; Martin, Nicholas G; Verhulst, Brad; Heath, Andrew C; Madden, Pamela A; Statham, Dixie J; Gillespie, Nathan A; ,
Journal	DRUG AND ALCOHOL DEPENDENCE
Pages	107704
Volume	205
Date	1/11/2019
Grant ID	APP10499110
Funding Body	National Health and Medical Research Council (NHMRC) in Australia
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.drugalcdep.2019.107704
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