Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index (original) (raw)

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 (h_SNP^2) of AN from these data is 0.20 (SE=0.02), suggesting that a substantial fracti...