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Am J Psychiatry DOI:10.1176/appi.ajp.2017.16121402

Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

Publication TypeJournal Article
Year of Publication2017
AuthorsDuncan, L, Yilmaz, Z, Gaspar, H, Walters, R, Goldstein, J, Anttila, V, Bulik-Sullivan, B, Ripke, S, Thornton, L, Hinney, A, Daly, M, Sullivan, PF, Zeggini, E, Breen, G, Bulik, CM
Corporate AuthorsEating Disorders Working Group of the Psychiatric Genomics Consortium
JournalAm J Psychiatry
Volume174
Issue9
Pages850-858
Date Published2017 09 01
ISSN1535-7228
KeywordsAnorexia Nervosa, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide
Abstract

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]), partitioned heritability, and genetic correlations (r) 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 hof 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.

DOI10.1176/appi.ajp.2017.16121402
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28494655?dopt=Abstract

Alternate JournalAm J Psychiatry
PubMed ID28494655
PubMed Central IDPMC5581217
Grant ListK01 MH109782 / MH / NIMH NIH HHS / United States
K01 MH106675 / MH / NIMH NIH HHS / United States
WT088827/Z/09 / / Wellcome Trust / United Kingdom
R01 DK075787 / DK / NIDDK NIH HHS / United States
/ / CIHR / Canada
U01 MH109514 / MH / NIMH NIH HHS / United States
K02 AA018755 / AA / NIAAA NIH HHS / United States
T32 MH076694 / MH / NIMH NIH HHS / United States
G0901245 / / Medical Research Council / United Kingdom
K01 MH093750 / MH / NIMH NIH HHS / United States
/ / Wellcome Trust / United Kingdom
U01 MH109539 / MH / NIMH NIH HHS / United States
R01 AA015416 / AA / NIAAA NIH HHS / United States
U01 MH094432 / MH / NIMH NIH HHS / United States
R01 MH092793 / MH / NIMH NIH HHS / United States
U01 MH109528 / MH / NIMH NIH HHS / United States
U01 HG006830 / HG / NHGRI NIH HHS / United States