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

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Authors
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, L Adrienne
Davis, Kathryn E
Döring, Angela
Eiriksdottir, Gudny
Estrada, Karol
Fernández-Real, José 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, José Maria
Männistö, Satu
O'Connell, Jeffery R
Pascoe, Laura
Peltonen, Leena
Peral, Belén
Perola, Markus
Psaty, Bruce M
Salomaa, Veikko
Savage, David B
Semple, Robert K
Skaric-Juric, Tatjana
Sigurdsson, Gunnar
Song, Kijoung S
Spector, Timothy D
Syvänen, Ann-Christine
Talmud, Philippa J
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Uitterlinden, André 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
Kiel, Douglas P
Rivadeneira, Fernando
Walker, Mark
Barroso, Inês
Vollenweider, Peter
Waeber, Gérard
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
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Issue Date
2011-08

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Citation
Nat. Genet. 2011, 43(8):753-60
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.
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To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links
http://dx.doi.org/10.1038/ng.866
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262230/?tool=pubmed
Rights
Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.866
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