Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic Correlations

Anorexia nervosa (AN) is a serious eating disorder characterized by restriction of energy intake relative to requirements, resulting in abnormally low body weight. It has a lifetime prevalence of approximately 1%, disproportionately affects females 1,2 , and has no well replicated evidence of effective pharmacological or psychological treatments despite high morbidity and mortality 2 . Twin studies support a genetic basis for the observed aggregation of AN in families 3 , with heritability estimates of 48%-74% 4 . Although initial genome-wide association studies (GWASs) were underpowered 5,6 , evidence suggested that signals for AN would be detected with increased power 5 . We present a GWAS of 3,495 AN cases and 10,982 controls with one genome-wide significant locus (index variant rs4622308, p=4.3x10 −9 ) in a region (chr12:56,372,585-56,482,185) which includes six genes. The SNP-chip heritability of AN from these data is 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability stems from common genetic variation. Using these GWAS results, we also find significant positive genetic correlations with schizophrenia, neuroticism, educational attainment, and HDL cholesterol, and significant negative genetic correlations with body mass, insulin, glucose, and lipid phenotypes. Our results support the reconceptualization of AN as a disorder with both psychiatric and metabolic components.