Genomics of body fat percentage may contribute to sex bias in anorexia nervosa
File(s)Genome Res.-2018-Cvetesic-gr.235937.118.pdf (1.25 MB)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-09-01
Date Acceptance
2018-11-26
Citation
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2019, 180 (6), pp.428-438
ISSN
1552-4841
Publisher
Wiley
Start Page
428
End Page
438
Journal / Book Title
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume
180
Issue
6
Copyright Statement
© 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30593698
Subjects
GWAS
eating disorder
fat-free mass
female
genetic correlation
shared genetics
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-12-28