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

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dc.contributor.authorDuncan, L.
dc.contributor.authorYilmaz, Z.
dc.contributor.authorGaspar, H.
dc.contributor.authorWalters, R.
dc.contributor.authorGoldstein, J.
dc.contributor.authorAnttila, V.
dc.contributor.authorBulik-Sullivan, B.
dc.contributor.authorRipke, S.
dc.contributor.authorThornton, L.
dc.contributor.authorHinney, A.
dc.contributor.authorDaly, M.
dc.contributor.authorSullivan, P.F.
dc.contributor.authorZeggini, E.
dc.contributor.authorBreen, G.
dc.contributor.authorBulik, C.M.
dc.contributor.authorGaspar, H.
dc.contributor.authorWalters, R.
dc.contributor.authorGoldstein, J.
dc.contributor.authorAdan, R.
dc.contributor.authorAlfredsson, L.
dc.contributor.authoret al.
dc.date.issued2017
dc.description.abstractObjective: 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 [h2SNP]), 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 h2SNP 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.
dc.description.statementofresponsibilityLaramie Duncan ... Sarah Cohen-Woods ... et al [Eating Disorders Working Group of the Psychiatric Genomics Consortium]
dc.identifier.citationAmerican Journal of Psychiatry, 2017; 174(9):850-858
dc.identifier.doi10.1176/appi.ajp.2017.16121402
dc.identifier.issn0002-953X
dc.identifier.issn1535-7228
dc.identifier.orcidCohen-Woods, S. [0000-0003-2199-6129]
dc.identifier.urihttp://hdl.handle.net/2440/120516
dc.language.isoen
dc.publisherAmerican Psychiatric Association Publishing
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/324715
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/480420
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/310667
dc.relation.grantDGR 3984/08
dc.relation.grantK01MH093750
dc.relation.grantK01MH106675
dc.relation.grantK01MH109782
dc.relation.grantR01 MH109528
dc.relation.grantD0886501
dc.rightsCopyright Status Unknown
dc.source.urihttps://doi.org/10.1176/appi.ajp.2017.16121402
dc.subjectEating disorders; genetics; anorexia nervosa; metabolism; GWAS; diabetes
dc.titleSignificant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa
dc.typeJournal article
pubs.publication-statusPublished

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