Genomics of body fat percentage may contribute to sex bias in anorexia nervosa

Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):428-438. doi: 10.1002/ajmg.b.32709. Epub 2018 Dec 28.


Anorexia nervosa (AN) occurs nine times more often in females than in males. Although environmental factors likely play a role, the reasons for this imbalanced sex ratio remain unresolved. AN displays high genetic correlations with anthropometric and metabolic traits. Given sex differences in body composition, we investigated the possible metabolic underpinnings of female propensity for AN. We conducted sex-specific GWAS in a healthy and medication-free subsample of the UK Biobank (n = 155,961), identifying 77 genome-wide significant loci associated with body fat percentage (BF%) and 174 with fat-free mass (FFM). Partitioned heritability analysis showed an enrichment for central nervous tissue-associated genes for BF%, which was more prominent in females than males. Genetic correlations of BF% and FFM with the largest GWAS of AN by the Psychiatric Genomics Consortium were estimated to explore shared genomics. The genetic correlations of BF%male and BF%female with AN differed significantly from each other (p < .0001, δ = -0.17), suggesting that the female preponderance in AN may, in part, be explained by sex-specific anthropometric and metabolic genetic factors increasing liability to AN.

Keywords: GWAS; eating disorder; fat-free mass; female; genetic correlation; shared genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adult
  • Anorexia Nervosa / genetics*
  • Anorexia Nervosa / metabolism*
  • Anorexia Nervosa / physiopathology
  • Body Composition / genetics*
  • Body Mass Index
  • Case-Control Studies
  • Databases, Genetic
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods
  • Genomics / methods
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Sex Factors