Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Cecilia M. Lindgren, Iris M. Heid, Joshua C. Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K. Speliotes, Gudmar Thorleifsson, Cristen J. Willer, Blanca M. Herrera, Anne U. Jackson, Noha Lim, Paul Scheet, Nicole Soranzo, Najaf Amin, Yurii S. Aulchenko, John C. Chambers, Alexander Drong, Jian'an Luan, Helen N. LyonFernando Rivadeneira, Serena Sanna, Nicholas J. Timpson, M. Carola Zillikens, Jing Hua Zhao, Peter Almgren, Stefania Bandinelli, Amanda J. Bennett, Richard N. Bergman, Lori L. Bonnycastle, Suzannah J. Bumpstead, Stephen J. Chanock, Lynn Cherkas, Peter Chines, Lachlan Coin, Cyrus Cooper, Gabriel Crawford, Angela Doering, Anna Dominiczak, Alex S. F. Doney, Shah Ebrahim, Paul Elliott, Michael R. Erdos, Karol Estrada, Luigi Ferrucci, Guido Fischer, Nita G. Forouhi, Colin N. A. Palmer, George Davey Smith, Andrew D. Morris, Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia

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    Abstract

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

    Original languageEnglish
    Article numbere1000508
    Pages (from-to)-
    Number of pages13
    JournalPLoS Genetics
    Volume5
    Issue number6
    DOIs
    Publication statusPublished - Jun 2009

    Keywords

    • FTO GENE
    • WAIST CIRCUMFERENCE
    • ADULT OBESITY
    • ENVIRONMENTAL-CONDITIONS
    • INSULIN-RESISTANCE
    • SEQUENCE VARIANTS
    • COMMON VARIANTS
    • EXPRESSION
    • IMPUTATION
    • HEIGHT

    Cite this

    Lindgren, C. M., Heid, I. M., Randall, J. C., Lamina, C., Steinthorsdottir, V., Qi, L., Speliotes, E. K., Thorleifsson, G., Willer, C. J., Herrera, B. M., Jackson, A. U., Lim, N., Scheet, P., Soranzo, N., Amin, N., Aulchenko, Y. S., Chambers, J. C., Drong, A., Luan, J., ... Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia (2009). Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genetics, 5(6), -. [e1000508]. https://doi.org/10.1371/journal.pgen.1000508