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Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

Duncan, L., Yilmaz, Z., Gaspar, H., Walters, R., Goldstein, J., Anttila, V., Bulik-Sullivan, B., Ripke, S., Thornton, L., Hinney, A., Daly, M., Sullivan, P. F., Zeggini, E., Breen, G., Bulik, C. M., Eating Disorders Working Group of the Psychiatric Genomics Consortium & Kas, M. J. H., 1-Sep-2017, In : American Journal of Psychiatry. 174, 9, p. 850-858

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  • Signi fi cant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa

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DOI

  • Laramie Duncan
  • Zeynep Yilmaz
  • Helena Gaspar
  • Raymond Walters
  • Jackie Goldstein
  • Verneri Anttila
  • Brendan Bulik-Sullivan
  • Stephan Ripke
  • Laura Thornton
  • Anke Hinney
  • Mark Daly
  • Patrick F Sullivan
  • Eleftheria Zeggini
  • Gerome Breen
  • Cynthia M Bulik
  • Eating Disorders Working Group of the Psychiatric Genomics Consortium
  • Martinus J.H. Kas

OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.

METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h(2)SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.

RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h(2)SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.

CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Original languageEnglish
Pages (from-to)850-858
JournalAmerican Journal of Psychiatry
Volume174
Issue number9
Publication statusPublished - 1-Sep-2017

    Keywords

  • Journal Article, PSYCHIATRIC-DISORDERS, EATING-DISORDERS, RISK, GWAS, SCHIZOPHRENIA, METAANALYSIS, TRAITS, UPDATE

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