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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile (CROSBI ID 173688)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Kilpeläinen, Tuomas O. ; Zillikens, M. Carola ; Stančákova, Alena ; Finucane, Francis M. ; Ried, Janina S. ; Langenberg, Claudia ; Zhang, Weihua ; Beckmann, Jacques S. ; Luan, Jian'an ; Vandenput, Liesbeth et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile // Nature genetics, 43 (2011), 8; 753-760. doi: 10.1038/ng.866

Podaci o odgovornosti

Kilpeläinen, Tuomas O. ; Zillikens, M. Carola ; Stančákova, Alena ; Finucane, Francis M. ; Ried, Janina S. ; Langenberg, Claudia ; Zhang, Weihua ; Beckmann, Jacques S. ; Luan, Jian'an ; Vandenput, Liesbeth ; Styrkarsdottir, Unnur ; Zhou, Yanhua ; Smith, Albert Vernon ; Zhao, Jing-Hua ; Amin, Najaf ; Vedantam, Sailaja ; Shin, So Youn ; Haritunians, Talin ; Fu, Mao ; Feitosa, Mary F. ; Kumari, Meena ; Halldorsson, Bjarni V. ; Tikkanen, Emmi ; Mangino, Massimo ; Hayward, Caroline ; Song, Ci ; Arnold, Alice M. ; Aulchenko, Yurii S. ; Oostra, Ben A. ; Campbell, Harry ; Cupples, Adrienne L. ; Davis, Kathryn E. ; Döring, Angela ; Eiriksdottir, Gudny ; Estrada, Karol ; Fernández-Real, Jose Manuel ; Garcia, Melissa ; Gieger, Christian ; Glazer, Nicole L. ; Guiducci, Candace ; Hofman, Albert ; Humphries, Steve E. ; Isomaa, Bo ; Jacobs, Leonie C. ; Jula, Antti ; Karasik, David ; Karlsson, Magnus K. ; Khaw, Kay-Tee ; Kim, Lauren J. ; Kivimäki, Mika ; Klopp, Norman ; Kühnel, Brigitte ; Kuusisto, Johanna ; Liu, Yongmei ; Ljunggren, Osten ; Lorentzon, Mattias ; Luben, Robert N. ; McKnight, Barbara ; Mellström, Dan ; Mitchell, Braxton D. ; Mooser, Vincent ; Moreno, Jose Maria ; Männistö, Satu ; O'Connell, Jeffery R. ; Pascoe, Laura ; Peltonen, Leena ; Peral, Belen ; Perola, Markus ; Psaty, Bruce M. ; Salomaa, Veikko ; Savage, David B. ; Semple, Robert K. ; Škarić-Jurić, Tatjana ; Sigurdsson, Gunnar ; Song, Kijoung S. ; Spector, Timothy D. ; Syvänen, Ann-Christine ; Talmud, Philippa J. ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Uitterlinden, Andre G. ; van Duijn, Cornelia M. ; Vidal-Puig, Antonio ; Wild, Sarah H. ; Wright, Alan F. ; Clegg, Deborah J. ; Schadt, Eric ; Wilson, James F. ; Rudan, Igor ; Ripatti, Samuli ; Borecki, Ingrid B. ; Shuldiner, Alan R. ; Ingelsson, Erik ; Jansson, John-Olov ; Kaplan, Robert C. ; Gudnason, Vilmundur ; Harris, Tamara B. ; Groop, Leif ; Kie, Douglas P. ; Rivadeneira, Fernando ; Walker, Mark ; Barroso, Ines ; Vollenweider, Peter ; Waeber, Gerard ; Chambers, John C. ; Kooner, Jaspal S. ; Soranzo, Nicole ; Hirschhorn, Joel N. ; Stefansson, Kari ; Wichmann, H.-Erich ; Ohlsson, Claes ; O'Rahilly, Stephen ; Wareham, Nicholas J. ; Speliotes, Elizabeth K. ; Fox, Caroline S. ; Laakso, Markku ; Loos, Ruth J.F.

engleski

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

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.

genome-wide association study; meta-analysis; fat distribution; adiposity; dyslipidemia; insulin resistance

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

43 (8)

2011.

753-760

objavljeno

1061-4036

10.1038/ng.866

Povezanost rada

Javno zdravstvo i zdravstvena zaštita, Etnologija i antropologija, Biologija

Poveznice
Indeksiranost