GWAS for anorexia nervosa finds 6 loci and suggests it is both a psychiatric and metabolic disease

Characterized primarily by extremely low BMI, anorexia nervosa (AN) is a complex, serious, and commonly misunderstood illness. Predominantly, but not exclusively affecting women, mortality from the illness and from suicide... [ view full abstract ]

Characterized primarily by extremely low BMI, anorexia nervosa (AN) is a complex, serious, and commonly misunderstood illness. Predominantly, but not exclusively affecting women, mortality from the illness and from suicide are markedly elevated, and outcomes remain unacceptably poor. AN is under-researched - no medications exist that are effective or target the core biology of the illness. Average twin-based heritability estimates are 50-60%, and genomic discovery in AN is just beginning. We conducted a genome-wide association study (GWAS) meta-analysis (15,807 cases and 50,411 controls) based on clinical, population-based, and volunteer cohorts and identified 6 independent genome-wide significant loci. Our analyses reveal high genetic correlations with obsessive-compulsive disorder (OCD), major depressive disorder (MDD), and anxiety disorders. However, we also observed strong negative genetic correlations between AN and fasting insulin levels, body fat percentage, and BMI as well as a strong positive genetic correlation between AN and high-density lipoprotein (HDL) cholesterol. These results may suggest that AN should be reconceptualised as both a psychiatric and metabolic disorder, though direction of causation also needs consideration.