Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Elizabeth K. Speliotes, Cristen J. Willer, Sonja I. Berndt, Keri L. Monda, Gudmar Thorleifsson, Anne U. Jackson, Hana Lango Allen, Cecilia M. Lindgren, Jian'an Luan, Reedik Maegi, Joshua C. Randall, Sailaja Vedantam, Thomas W. Winkler, Lu Qi, Tsegaselassie Workalemahu, Iris M. Heid, Valgerdur Steinthorsdottir, Heather M. Stringham, Michael N. Weedon, Eleanor WheelerAndrew R. Wood, Teresa Ferreira, Robert J. Weyant, Ayellet V. Segre, Karol Estrada, Liming Liang, James Nemesh, Ju-Hyun Park, Stefan Gustafsson, Tuomas O. Kilpelaenen, Jian Yang, Nabila Bouatia-Naji, Tonu Esko, Mary F. Feitosa, Zoltan Kutalik, Massimo Mangino, Soumya Raychaudhuri, Andre Scherag, Albert Vernon Smith, Ryan Welch, Jing Hua Zhao, Katja K. Aben, Devin M. Absher, Najaf Amin, Anna L. Dixon, Eva Fisher, Nicole L. Glazer, Michael E. Goddard, Nancy L. Heard-Costa, John Connell, MAGIC

    Research output: Contribution to journalArticlepeer-review

    2395 Citations (Scopus)

    Abstract

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

    Original languageEnglish
    Pages (from-to)937-U53
    Number of pages14
    JournalNature Genetics
    Volume42
    Issue number11
    DOIs
    Publication statusPublished - Nov 2010

    Keywords

    • GENOME-WIDE ASSOCIATION
    • GASTRIC-INHIBITORY POLYPEPTIDE
    • MELANOCORTIN-4 RECEPTOR GENE
    • GLUCOSE-HOMEOSTASIS
    • COMMON VARIANTS
    • ADULT OBESITY
    • EARLY-ONSET
    • FTO GENE
    • FAT MASS
    • RISK

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