Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
Volume 180, Issue 6, Pages 428-438Publisher
WILEY
DOI: 10.1002/ajmg.b.32709
Keywords
eating disorder; fat-free mass; female; genetic correlation; GWAS; shared genetics
Categories
Funding
- GSTT Charity [TR130505]
- Maudsley Charity [TR130505, 980]
- NIH [R01HD057194]
- UK Medical Research Council [MR/N015746/1]
- Vetenskapsradet [538-2013-8864]
- Wellcome Trust [109863/Z/15/Z]
- National Institutes of Health [R01HD057194]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Medical Research Council
- Klarman Family Foundation
- Swedish Research Council
- South London and Maudsley NHS Foundation Trust
- National Institute for Health Research
- Wellcome Trust [109863/Z/15/Z] Funding Source: Wellcome Trust
- MRC [1668713, MR/N015746/1] Funding Source: UKRI
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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, delta = -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.
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