Genomics of Body Fat Percentage May Contribute to Sex Bias in Anorexia Nervosa

Overview

Journal Am J Med Genet B Neuropsychiatr Genet

Specialties Genetics
Neurology
Psychiatry

Date 2018 Dec 30

PMID 30593698

Citations 51

Authors

Christopher Hubel

Helena A Gaspar

Jonathan R I Coleman

Hilary Finucane

Kirstin L Purves

Ken B Hanscombe

Inga Prokopenko

Mariaelisa Graff

Julius S Ngwa

Tsegaselassie Workalemahu

Paul F OReilly

Cynthia M Bulik

Gerome Breen

Affiliations

Soon will be listed here.

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% and BF% 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.

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