Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

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Serval ID
serval:BIB_342B86FD2B66
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
Journal
Nature Genetics
Author(s)
Kilpeläinen T.O., Zillikens M.C., Stančákova A., Finucane F.M., Ried J.S., Langenberg C., Zhang W., Beckmann J.S., Luan J., Vandenput L., Styrkarsdottir U., Zhou Y., Smith A.V., Zhao J.H., Amin N., Vedantam S., Shin S.Y., Haritunians T., Fu M., Feitosa M.F., Kumari M., Halldorsson B.V., Tikkanen E., Mangino M., Hayward C., Song C., Arnold A.M., Aulchenko Y.S., Oostra B.A., Campbell H., Cupples L.A., Davis K.E., Döring A., Eiriksdottir G., Estrada K., Fernández-Real J.M., Garcia M., Gieger C., Glazer N.L., Guiducci C., Hofman A., Humphries S.E., Isomaa B., Jacobs L.C., Jula A., Karasik D., Karlsson M.K., Khaw K.T., Kim L.J., Kivimäki M., Klopp N., Kühnel B., Kuusisto J., Liu Y., Ljunggren O., Lorentzon M., Luben R.N., McKnight B., Mellström D., Mitchell B.D., Mooser V., Moreno J.M., Männistö S., O'Connell J.R., Pascoe L., Peltonen L., Peral B., Perola M., Psaty B.M., Salomaa V., Savage D.B., Semple R.K., Skaric-Juric T., Sigurdsson G., Song K.S., Spector T.D., Syvänen A.C., Talmud P.J., Thorleifsson G., Thorsteinsdottir U., Uitterlinden A.G., van Duijn C.M., Vidal-Puig A., Wild S.H., Wright A.F., Clegg D.J., Schadt E., Wilson J.F., Rudan I., Ripatti S., Borecki I.B., Shuldiner A.R., Ingelsson E., Jansson J.O., Kaplan R.C., Gudnason V., Harris T.B., Groop L., Kiel D.P., Rivadeneira F., Walker M., Barroso I., Vollenweider P., Waeber G., Chambers J.C., Kooner J.S., Soranzo N., Hirschhorn J.N., Stefansson K., Wichmann H.E., Ohlsson C., O'Rahilly S., Wareham N.J., Speliotes E.K., Fox C.S., Laakso M., Loos R.J.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
2011
Volume
43
Number
8
Pages
753-760
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
Publication Status: epublish
Abstract
Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
Keywords
Adiponectin/blood, Adiposity/genetics, Alleles, Body Fat Distribution, Body Mass Index, Body Weight, Female, Genetic Variation/genetics, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins/genetics, Intracellular Signaling Peptides and Proteins/genetics, Male, Meta-Analysis as Topic, Metabolome/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Subcutaneous Fat
Pubmed
Web of science
Create date
29/06/2011 9:21
Last modification date
20/08/2019 13:20
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