Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
Journal article
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 V., Zhao, Jing-Hua, Amin, Najaf, Vedantam, Sailaja, Shin, So-Youn, Haritunians, Talin, Fu, Mao, ... Loos, Ruth J. F.. (2011). Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nature Genetics. 43(8), pp. 753 - 760. https://doi.org/10.1038/ng.866
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 V., 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, Östen, 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 and Loos, Ruth J. F. |
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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. |
Year | 2011 |
Journal | Nature Genetics |
Journal citation | 43 (8), pp. 753 - 760 |
Publisher | Nature Publishing Group |
ISSN | 1061-4036 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/ng.866 |
Scopus EID | 2-s2.0-79960895140 |
Page range | 753 - 760 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/8q393/genetic-variation-near-irs1-associates-with-reduced-adiposity-and-an-impaired-metabolic-profile
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