The Interrelationship of the Genetic Risks for Different Forms of Substance Use Disorder in a Swedish National Sample : A Top-Down Genetic Analysis

Objective: The purpose of this study was to determine, using a top-down genetic analysis, the degree of specificity of the genetic risk factors for individual forms of substance use disorders (SUD). Method: We examined and followed to December 31, 2018, all individuals born in Sweden between 1960 and 1990 (N = 2,772,752) diagnosed with any of the following six SUDs: alcohol use disorder (AUD), drug use disorder (DUD), or one of four specific forms of DUD involving cannabis (CUD), cocaine and other stimulants (CSUD), opioids (OUD), or sedatives (SeUD). We examined population subsamples at high versus median genetic liability to each of these SUDs. In those samples, we then examined the prevalence of our SUDs in the high versus median liability groups, expressed as a tetrachoric correlation. Genetic liability was assessed by a family genetic risk score. Results: All SUDs were concentrated in those at high versus median risk for all six groups. DUD, CUD, and CSUD showed modest genetic specificity in that they were more concentrated in samples with high genetic liability to each of them than were other SUDs. The differences, however, were modest. No evidence for genetic specificity was seen for AUD, OUD, and SeUD, as other disorders were equally or more concentrated in those at high versus median genetic risk for that form of SUD. Conclusions: Individuals at high genetic risk for particular forms of SUD typically had elevated rates for all forms of SUDs, consistent with the nonspecificity of much of SUD genetic liability. Evidence of specificity of genetic risk for particular forms of SUD was noted but was quantitatively modest. (J. Stud. Alcohol Drugs, 84, 361–367, 2023)