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

Melissa A. Munn-Chernoff, Tatiana M. Foroud, Emma C. Johnson, Nathan A. Gillespie, Yi-Ling Chou, Alison M. Goate, Jonathan R. I. Coleman, David Goldman, Laura M. Thornton, Richard A. Grucza, …
bioRxiv
Cold Spring Harbor Laboratory
08/23/2019
DOI: 10.1101/741512
url
https://doi.org/10.1111/adb.12880View
Published (Version of record)This article has now been published in a journal and has been peer-reviewed by subject experts. This version may differ significantly from the preprint version.
url
https://doi.org/10.1101/741512View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [ r g ], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). 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. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). 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 ( r g =0.18; false discovery rate q =0.0006), cannabis initiation and AN ( r g =0.23; q <0.0001), and cannabis initiation and AN with binge-eating ( r g =0.27; q =0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating ( r gs =-0.19 to −0.23; qs <0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for MDD loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships between these behaviors.

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