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

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.

doi:10.1038/ng.866

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

Détails

Télécharger: 21706003_Postprint.pdf (1609.78 [Ko])
Etat: Public
Version: de l'auteur⸱e

ID Serval

serval:BIB_342B86FD2B66

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

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

Périodique

Nature Genetics

Auteur⸱e⸱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

Statut éditorial

Publié

Date de publication

2011

Volume

Numéro

Pages

753-760

Langue

anglais

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

Résumé

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.

Mots-clé

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

URN

urn:nbn:ch:serval-BIB_342B86FD2B660

OAI-PMH

oai:serval.unil.ch:BIB_342B86FD2B66

DOI

10.1038/ng.866

Pubmed

21706003

Web of science

000293178300011

Création de la notice

29/06/2011 10:21