A genome-wide association study of anorexia nervosa

Area of Science:

• Genetics
• Psychiatry
• Eating Disorders

Background:

• Anorexia nervosa (AN) is a complex eating disorder with a significant heritable component.
• Previous genetic studies, including genome-wide association studies (GWAS), have not identified robustly replicated genetic risk factors for AN.
• The Genetic Consortium for AN (GCAN) and Wellcome Trust Case Control Consortium 3 (WTCCC3) aimed to expand the genetic investigation of AN.

Purpose of the Study:

• To conduct a large-scale GWAS to identify genetic variants associated with anorexia nervosa.
• To meta-analyze results from discovery and replication cohorts to increase statistical power.
• To investigate potential genetic associations within AN subtypes (restricting and binge-purge).

Main Methods:

• A genome-wide association study (GWAS) was performed on 2907 anorexia nervosa (AN) cases and 14,860 controls.
• Seventy-six single nucleotide polymorphisms (SNPs) were selected for replication genotyping in additional AN cases and controls.
• A final global meta-analysis combined discovery and replication data, totaling 5551 AN cases and 21,080 controls.

Main Results:

• No single nucleotide polymorphisms (SNPs) reached the stringent threshold for genome-wide significance.
• Suggestive associations were observed for two intronic variants (rs9839776 in SOX2OT and rs17030795 in PPP3CA).
• Two additional signals were identified specifically in European ancestry cohorts (rs1523921 and rs1886797).

Conclusions:

• While this study, the largest GWAS for AN to date, did not identify genome-wide significant loci, the directional consistency of effects suggests true associations may exist.
• The current sample size appears underpowered to detect these true genetic findings.
• There is a critical need to increase the sample size of genotyped anorexia nervosa case-control cohorts for future genetic discoveries.