Shared Genetic Risk between Eating Disorder and Substance Use-Related Phenotypes: Evidence from Genome-Wide Association Studies

Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic risk between eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use, mainly abuse and dependence (twin-based genetic correlation [rg]=0.23–0.53). Analytic advances facilitate the computation of genetic correlations using summary statistics from existing genome-wide association studies (GWAS). We investigated shared genetic risk between eating disorder and substance use and disorder phenotypes using GWAS data. Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; q<0.0001), and cannabis initiation and AN with binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, smoking cessation, and cigarettes per day) and AN without binge-eating (rgs=−0.19 to −0.23; qs<0.04). The observed patterns of association between different eating disorder and substance use-related phenotypes highlights the potentially complex and substance-specific relationships between these behaviors associated with significant public health burden.