학술논문
Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa
Document Type
article
Author
Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M; Gaspar, Héléna; Adan, Roger; Alfredsson, Lars; Ando, Tetsuya; Andreassen, Ole; Aschauer, Harald; Baker, Jessica; Barrett, Jeffrey; Bencko, Vladimir; Bergen, Andrew; Berrettini, Wade; Birgegård, Andreas; Boni, Claudette; Perica, Vesna Boraska; Brandt, Harry; Burghardt, Roland; Carlberg, Laura; Cassina, Matteo; Cesta, Carolyn; Cichon, Sven; Clementi, Maurizio; Cohen-Woods, Sarah; Coleman, Joni; Cone, Roger; Courtet, Philippe; Crawford, Steven; Crow, Scott; Crowley, Jim; Danner, Unna; Davis, Oliver; de Zwaan, Martina; Dedoussis, George; Degortes, Daniela; DeSocio, Janiece; Dick, Danielle; Dikeos, Dimitris; Dina, Christian; Ding, Bo; Dmitrzak-Weglarz, Monika; Docampo, Elisa; Egberts, Karin; Ehrlich, Stefan; Escaramís, Geòrgia; Esko, Tõnu; Espeseth, Thomas; Estivill, Xavier; Favaro, Angela; Fernández-Aranda, Fernando; Fichter, Manfred; Finan, Chris; Fischer, Krista; Floyd, James; Föcker, Manuel; Foretova, Lenka; Forzan, Monica; Fox, Caroline; Franklin, Christopher; Gaborieau, Valerie; Gallinger, Steven; Gambaro, Giovanni; Giegling, Ina; Gonidakis, Fragiskos; Gorwood, Philip; Gratacos, Monica; Guillaume, Sébastien; Guo, Yiran; Hakonarson, Hakon; Halmi, Katherine; Harrison, Rebecca; Hatzikotoulas, Konstantinos; Hauser, Joanna; Hebebrand, Johannes; Helder, Sietske; Hendriks, Judith; Herms, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Hilliard, Christopher
Source
American Journal of Psychiatry. 174(9)
Subject
Language
Abstract
ObjectiveThe authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.MethodFollowing 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.ResultsResults 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.ConclusionsAnorexia 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.