Human metabolic individuality in biomedical and pharmaceutical research.

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Serval ID
serval:BIB_AC1AF700E07A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
UNIL/CHUV
Title
Human metabolic individuality in biomedical and pharmaceutical research.
Journal
Nature
Author(s)
Suhre K., Shin S.Y., Petersen A.K., Mohney R.P., Meredith D., Wägele B., Altmaier E., CARDIoGRAM , Deloukas P., Deloukas P., Erdmann J., Grundberg E., Hammond C.J., de Angelis M.H., Kastenmüller G., Köttgen A., Kronenberg F., Mangino M., Meisinger C., Meitinger T., Mewes H.W., Milburn M.V., Prehn C., Raffler J., Ried J.S., Römisch-Margl W., Samani N.J., Small K.S., Wichmann H.E., Zhai G., Illig T., Spector T.D., Adamski J., Soranzo N., Gieger C.
Contributor(s)
CARDIoGRAM , Kathiresan S., Reilly MP., Samani NJ., Schunkert H., Erdmann J., Assimes TL., Boerwinkle E., Erdmann J., Hall A., Hengstenberg C., Kathiresan S., König IR., Laaksonen R., McPherson R., Reilly MP., Samani NJ., Schunkert H., Thompson JR., Thorsteinsdottir U., Ziegler A., König IR., Thompson JR., Absher D., Chen L., Cupples LA., Halperin E., Li M., Musunuru K., Preuss M., Schillert A., Thorleifsson G., Voight BF., Wells GA., Absher D., Assimes TL., Deloukas P., Erdmann J., Holm H., Kathiresan S., König IR., McPherson R., Reilly MP., Roberts R., Samani NJ., Schunkert H., Stewart AF., Fortmann S., Go A., Hlatky M., Iribarren C., Knowles J., Myers R., Quertermous T., Sidney S., Risch N., Tang H., Blankenberg S., Zeller T., Schillert A., Wild P., Ziegler A., Schnabel R., Sinning C., Lackner K., Tiret L., Nicaud V., Cambien F., Bickel C., Rupprecht HJ., Perret C., Proust C., Münzel T., Barbalic M., Bis J., Boerwinkle E., Chen IY., Cupples LA., Dehghan A., Demissie-Banjaw S., Folsom A., Glazer N., Gudnason V., Harris T., Heckbert S., Levy D., Lumley T., Marciante K., Morrison A., O'Donnell CJ., Psaty BM., Rice K., Rotter JI., Siscovick DS., Smith N., Smith A., Taylor KD., van Duijn C., Volcik K., Whitteman J., Ramachandran V., Hofman A., Uitterlinden A., Gretarsdottir S., Gulcher JR., Holm H., Kong A., Stefansson K., Thorgeirsson G., Andersen K., Thorleifsson G., Thorsteinsdottir U., Erdmann J., Fischer M., Grosshennig A., Hengstenberg C., König IR., Lieb W., Linsel-Nitschke P., Preuss M., Stark K., Schreiber S., Wichmann HE., Ziegler A., Schunkert H., Aherrahrou Z., Bruse P., Doering A., Erdmann J., Hengstenberg C., Illig T., Klopp N., König IR., Linsel-Nitschke P., Loley C., Medack A., Meisinger C., Meitinger T., Nahrstedt J., Peters A., Preuss M., Stark K., Wagner AK., Wichmann HE., Willenborg C., Ziegler A., Schunkert H., Böhm BO., Dobnig H., Grammer TB., Halperin E., Hoffmann MM., Kleber M., Laaksonen R., März W., Meinitzer A., Winkelmann BR., Pilz S., Renner W., Scharnagl H., Stojakovic T., Tomaschitz A., Winkler K., Voight BF., Musunuru K., Guiducci C., Burtt N., Gabriel SB., Siscovick DS., O'Donnell CJ., Elosua R., Peltonen L., Salomaa V., Schwartz SM., Melander O., Altshuler D., Kathiresan S., Stewart AF., Chen L., Dandona S., Wells GA., Jarinova O., McPherson R., Roberts R., Reilly MP., Li M., Qu L., Wilensky R., Matthai W., Hakonarson HH., Devaney J., Burnett MS., Pichard AD., Kent KM., Satler L., Lindsay JM., Waksman R., Knouff CW., Waterworth DM., Walker MC., Mooser V., Epstein SE., Rader DJ., Samani NJ., Thompson JR., Braund PS., Nelson CP., Wright BJ., Balmforth AJ., Ball SG., Hall AS.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
2011
Volume
477
Number
7362
Pages
54-60
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Biomedical Research, Blood/metabolism, Child, Chronic Disease, Coronary Artery Disease/genetics, Diabetes Mellitus/genetics, Drug Industry, Female, Genetic Loci/genetics, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Metabolism/genetics, Metabolomics, Middle Aged, Pharmacogenetics, Renal Insufficiency/genetics, Risk Factors, Venous Thromboembolism/genetics, Young Adult
OAI-PMH
oai:serval.unil.ch:BIB_AC1AF700E07A
DOI
10.1038/nature10354
Pubmed
21886157
Web of science
000294404300029
Create date
22/03/2012 10:44
Last modification date
20/08/2019 16:16
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