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

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DOI

  • Christopher Hübel, King's College London, South London and Maudsley NHS Foundation Trust, Karolinska Institutet
  • ,
  • Héléna A. Gaspar, King's College London, South London and Maudsley Hospital
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  • Jonathan R.I. Coleman, King's College London, South London and Maudsley Hospital
  • ,
  • Hilary Finucane, Broad Institute
  • ,
  • Kirstin L. Purves, King's College London
  • ,
  • Ken B. Hanscombe, King's College London
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  • Inga Prokopenko, Imperial College London, London, UK.
  • ,
  • Mariaelisa Graff, University of North Carolina
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  • Julius S. Ngwa, Johns Hopkins Bloomberg School of Public Health, Boston University School of Public Health
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  • Tsegaselassie Workalemahu, National Institutes of Health
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  • Paul F. O'Reilly, King's College London
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  • Cynthia M. Bulik, Karolinska Institutet, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
  • ,
  • Gerome Breen, King's College London, South London and Maudsley Hospital
  • ,
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
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  • Schizophrenia Working Group of the Psychiatric Genomics Consortium
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  • Tourette Syndrome/Obsessive-Compulsive Disorder Working Group of the Psychiatric Genomics Consortium
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  • MAGIC Investigators
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  • Eating Disorders Working Group of the Psychiatric Genomics Consortium
  • ,
  • Manuel Mattheisen (Member of author collaboration)
  • Jakob Grove (Member of author collaboration)
  • Preben Bo Mortensen (Member of author collaboration)

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.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume180
Issue6
Pages (from-to)428-438
Number of pages11
ISSN1552-4841
DOIs
Publication statusPublished - Sep 2019

    Research areas

  • eating disorder, fat-free mass, female, genetic correlation, GWAS, shared genetics, GENETIC-BASIS, METAANALYSIS, MASS INDEX, LOCI, HERITABILITY, RISK-FACTOR, GLYCEMIC TRAITS, POOLED ANALYSIS, WIDE ASSOCIATION, BIOLOGICAL INSIGHTS

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