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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Watson, Hunna J ; Yilmaz, Zeynep ; Thornton, Laura M ; Bryois, Julien ; Mattheisen, Manuel ; Ripke, Stephan ; Yao, Shuyang ; Adan, Roger A H ; Ando, Tetsuya ; Andreassen, Ole A ; Perica, Vesna Boraska ; Buehren, Katharina ; Burghardt, Roland ; Cichon, Sven ; Clementi, Maurizio ; Cone, Roger D ; Courtet, Philippe ; Crowley, James J ; de Zwaan, Martina ; Dedoussis, George ; Degortes, Daniela ; Dick, Danielle M ; Dikeos, Dimitris ; Dina, Christian ; Docampo, Elisa ; Duncan, Laramie E ; Escaramís, Geòrgia ; Estivill, Xavier ; Fernández-Aranda, Fernando ; Fichter, Manfred M ; Foretova, Lenka ; Forstner, Andreas J ; Gallinger, Steven ; Guillaume, Sébastien ; Hakonarson, Hakon ; Hatzikotoulas, Konstantinos ; Hauser, Joanna ; Helder, Sietske G ; Herms, Stefan ; Herzog, Wolfgang ; Janout, Vladimir ; Julià, Antonio ; Kaminská, Deborah ; Kaprio, Jaakko ; Kas, Martien J H ; Kennedy, James L ; Keski-Rahkonen, Anna ; Kiezebrink, Kirsty ; Kim, Youl-Ri ; Klareskog, Lars ; Klump, Kelly L ; La Via, Maria C ; Lissowska, Jolanta ; Luykx, Jurjen ; Magistretti, Pierre J ; Maj, Mario ; Mattingsdal, Morten ; Metspalu, Andres ; Micali, Nadia ; Ophoff, Roel A ; Padyukov, Leonid ; Rabionet, Raquel ; Raevuori, Anu ; Ramoz, Nicolas ; Reichborn-Kjennerud, Ted ; Ripatti, Samuli ; Roberts, Marion ; Rotondo, Alessandro ; Rujescu, Dan ; Scherer, Stephen W ; Schmidt, Ulrike ; Sorbi, Sandro ; Świątkowska, Beata ; Szatkiewicz, Jin P ; Tenconi, Elena ; Tortorella, Alfonso ; Tsitsika, Artemis ; Tyszkiewicz-Nwafor, Marta ; Tziouvas, Konstantinos ; van Elburg, Annemarie A ; van Furth, Eric F ; Wagner, Gudrun ; Walton, Esther ; Widen, Elisabeth ; Zipfel, Stephan ; Boden, Joseph M ; Brandt, Harry ; Halmi, Katherine A ; Johnson, Craig ; Kaye, Walter H ; Pearson, John F ; Whiteman, David C ; Gordon, Scott ; Jordan, Jennifer ; Kennedy, Martin ; Wade, Tracey D ; Lichtenstein, Paul ; Mortensen, Preben Bo ; Sullivan, Patrick F ; Breen, Gerome

Nature genetics, 2019-08, Vol.51 (8), p.1207-1214 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
Autor: Watson, Hunna J ; Yilmaz, Zeynep ; Thornton, Laura M ; Bryois, Julien ; Mattheisen, Manuel ; Ripke, Stephan ; Yao, Shuyang ; Adan, Roger A H ; Ando, Tetsuya ; Andreassen, Ole A ; Perica, Vesna Boraska ; Buehren, Katharina ; Burghardt, Roland ; Cichon, Sven ; Clementi, Maurizio ; Cone, Roger D ; Courtet, Philippe ; Crowley, James J ; de Zwaan, Martina ; Dedoussis, George ; Degortes, Daniela ; Dick, Danielle M ; Dikeos, Dimitris ; Dina, Christian ; Docampo, Elisa ; Duncan, Laramie E ; Escaramís, Geòrgia ; Estivill, Xavier ; Fernández-Aranda, Fernando ; Fichter, Manfred M ; Foretova, Lenka ; Forstner, Andreas J ; Gallinger, Steven ; Guillaume, Sébastien ; Hakonarson, Hakon ; Hatzikotoulas, Konstantinos ; Hauser, Joanna ; Helder, Sietske G ; Herms, Stefan ; Herzog, Wolfgang ; Janout, Vladimir ; Julià, Antonio ; Kaminská, Deborah ; Kaprio, Jaakko ; Kas, Martien J H ; Kennedy, James L ; Keski-Rahkonen, Anna ; Kiezebrink, Kirsty ; Kim, Youl-Ri ; Klareskog, Lars ; Klump, Kelly L ; La Via, Maria C ; Lissowska, Jolanta ; Luykx, Jurjen ; Magistretti, Pierre J ; Maj, Mario ; Mattingsdal, Morten ; Metspalu, Andres ; Micali, Nadia ; Ophoff, Roel A ; Padyukov, Leonid ; Rabionet, Raquel ; Raevuori, Anu ; Ramoz, Nicolas ; Reichborn-Kjennerud, Ted ; Ripatti, Samuli ; Roberts, Marion ; Rotondo, Alessandro ; Rujescu, Dan ; Scherer, Stephen W ; Schmidt, Ulrike ; Sorbi, Sandro ; Świątkowska, Beata ; Szatkiewicz, Jin P ; Tenconi, Elena ; Tortorella, Alfonso ; Tsitsika, Artemis ; Tyszkiewicz-Nwafor, Marta ; Tziouvas, Konstantinos ; van Elburg, Annemarie A ; van Furth, Eric F ; Wagner, Gudrun ; Walton, Esther ; Widen, Elisabeth ; Zipfel, Stephan ; Boden, Joseph M ; Brandt, Harry ; Halmi, Katherine A ; Johnson, Craig ; Kaye, Walter H ; Pearson, John F ; Whiteman, David C ; Gordon, Scott ; Jordan, Jennifer ; Kennedy, Martin ; Wade, Tracey D ; Lichtenstein, Paul ; Mortensen, Preben Bo ; Sullivan, Patrick F ; Breen, Gerome
Assuntos: Adult ; Analysis ; Anorexia ; Anorexia nervosa ; Anorexia Nervosa - etiology ; Anorexia Nervosa - genetics ; Anorexia Nervosa - pathology ; Anthropometry ; Bioinformatics ; Body Mass Index ; Case-Control Studies ; Causes of ; Chromosomes ; Colorectal cancer ; comorbidity ; Consortia ; Diabetes ; Diagnosis ; Disorders ; Eating disorders ; Female ; Gene loci ; Genetic aspects ; genetic correlations ; Genetic Predisposition to Disease ; Genetics ; Genetics & genetic processes ; Genetics & Heredity ; Genetik ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Genomics - methods ; Génétique & processus génétiques ; Heritability ; Humans ; insights ; ld score regression ; Life Sciences ; Lipids ; Male ; Medicin och hälsovetenskap ; Mental disorders ; Mental Disorders - complications ; Mental Disorders - genetics ; Metabolic Diseases - complications ; Metabolic Diseases - genetics ; Metabolism ; myc ; Phenotype ; Physical activity ; polygenic ; prevalence ; Prognosis ; Quantitative Trait Loci ; risk ; Schizophrenia ; Sciences du vivant ; variants ; Working groups
É parte de: Nature genetics, 2019-08, Vol.51 (8), p.1207-1214
Notas: PMCID: PMC6779477
scopus-id:2-s2.0-85068455956
The members of this consortium are listed in the Supplementary Note
These authors contributed equally to this work
These authors jointly directed this project
C.M.B. and P.F.S. conceived and designed the study. L.T., C.M.B., and G.B. performed overall study coordination. C.M.B. was lead PI of ANGI. P.F.S. was Co-Investigator of ANGI. N.G.M., M.L., and P.B.M. were site PIs of ANGI. H.J.W., Z.Y., J.R.I.C., C.H., J.B., H.A.G., S.Y., V.M.L., M.M., P.G-R. and S.E.M. performed the statistical analyses. H.J.W., Z.Y., C.H., J.R.I.C., H.A.G., J.B., A.H., P.G-R., P.F.S., G.B. and C.M.B. comprised the writing group. C.M.B. and G.B. were PGC-ED co-chairs. S.R. provided statistical consultation. A.H. assisted with data interpretation. A.W.B., C.M.B., J.J., M.K., K.M.K., P.L., G.M., C.N., R.P., L.T., and T.D.W. collected and managed the ANGI samples at sites and assisted with site-specific study co-ordination. A.W.B., J.M.B., H.B., S.C., K.A.H., L.J.H., C.J., A.S.K., W.K., J.M., C.M.O., J.F.P., N.L.P., M.S., T.W., D.C.W., and D.B.W. provided ANGI controls and extra samples. L.E.D provided data expertise. S.G., J.G., A.K.H., A.J., K.M.K., J.T.L., R.P., and L.P. contributed to the ANGI study. S.G., J.G., K.K., J.T.L., M.M., S.M., and L.P. were ANGI site analysts. K.B.H. and K.L.P. provided additional analysis for some secondary analyses. G.W.M., T.D.W., A.B., P.L., and C.N. were ANGI investigators. J.J. and M.K. assisted with ANGI recruitment in NZ. C.M.B., G.B., and P.F.S. supervised the study. H.J.W., C.M.B., Z.Y., C.H., G.B., J.R.I.C., H.A.G., S.Y., J.B., P.F.S., and P.G. wrote the manuscript. PGC-ED members and other individuals contributed to sample acquisition and made individual data from subjects available: R.A.H.A., L.A. T.A., O.A.A., J.H.B., A.W.B., W.H.B., A.B., I.B., C.B., J.M.B., H.B., G.B., K. B., C.M.B., R.B., M.C., S.C., M.C., J.R.I.C., R.D.C., P.C., S.C., S.C., J.C., U.N.D., O.S.P.D, M.D, G.D., D.D., J.E.D., D.M.D., D.D., C.D., M.D., E.D.M., K.E., S.E., G.E., T.E., X.E., A.F., A.F., F.F., M.M.F., K.F., M.F., L.F., A.J.F., M.F., S.G., I.G., J.G., F.G., S.G., P.G., M.G.M., J.G., S.G., K.A.H., K.H., J.H., J.H., S.G.H., A.K.H., S.H., B.H., W.H., A.H., L.J.H., J.I.H., H.I., H.I., V.J., S.J., C.J., J.J., A.J., A.J., G.K., D.K., A.S.K., J.K,. L.K., A.K., M.J.H.K., W.K., J.L.K., M.K., A.K., K.K., Y.K., L.K., G.S.K., M.C.L, M.L., S.L., R.D.L., P.L., L.L., B.L., J.L., J.L., P.M., M.M., K.M., S.M., C.M., N.G.M., M.M., S.M., P.M., A.M., I.M., N.M., J.M., A.M.M., P.M., P.M., M.A.M., B.N., M.N., C.N., I.N., C.M.O., J.K.O., R.A.O., L.P., A.P., J.P., H.P., N.L.P., J.F.P., D.P., R.R., A.R., N.R., T.R., V.R., S.R., F.R., M.R., A.R., D.R., F.R., P.S., S.W.S., U.S., A.S., J.S., L.S., P.E.S., M.C.T.S.L., A.S., S.S., M.S., P.F.S., B.Ś., J.P.S., I.T., E.T., A.T., F.T., J.T., A.T., M.T., K.T., A.A.V, E.F.V., T.D.W., G.W., E.W., H.J.W., T.W., D.C.W., E.W., D.B.W., G.S., S.Z., and S.Z. All authors critically reviewed the manuscript.
Author contributions
Descrição: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness , affecting 0.9-4% of women and 0.3% of men , with twin-based heritability estimates of 50-60% . Mortality rates are higher than those in other psychiatric disorders , and outcomes are unacceptably poor . Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

United States: Nature Publishing Group

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