RT Journal Article
SR Electronic
T1 Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic Correlations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 088815
DO 10.1101/088815
A1 E. L. Duncan
A1 L. M. Thornton
A1 A. Hinney
A1 M. J. Daly
A1 P. F. Sullivan
A1 E. Zeggini
A1 G. Breen
A1 C. M. Bulik
YR 2016
UL http://biorxiv.org/content/early/2016/11/25/088815.abstract
AB 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 females1,2, and has no well replicated evidence of effective pharmacological or psychological treatments despite high morbidity and mortality2. Twin studies support a genetic basis for the observed aggregation of AN in families3, with heritability estimates of 48%-74%4. Although initial genome-wide association studies (GWASs) were underpowered5,6, evidence suggested that signals for AN would be detected with increased power5. 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.