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Am J Med Genet B Neuropsychiatr Genet. 2018 Dec 28. doi: 10.1002/ajmg.b.32709. [Epub ahead of print]

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

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Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
UK National Institute for Health Research (NIHR) Biomedical Research Centre, South London and Maudsley Hospital, London, United Kingdom.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Schmidt Fellows Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, United Kingdom.
Section of Genomics of Common Disease, Department of Medicine, Imperial College London, London, United Kingdom.
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.


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.


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


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