Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Cristen J. Willer, Elizabeth K. Speliotes, Ruth J. F. Loos, Shengxu Li, Cecilia M. Lindgren, Iris M. Heid, Sonja I. Berndt, Amanda L. Elliott, Anne U. Jackson, Claudia Lamina, Guillaume Lettre, Noha Lim, Helen N. Lyon, Steven A. McCarroll, Konstantinos Papadakis, Lu Qi, Joshua C. Randall, Rosa Maria Roccasecca, Serena Sanna, Paul ScheetMichael N. Weedon, Eleanor Wheeler, Jing Hua Zhao, Leonie C. Jacobs, Inga Prokopenko, Nicole Soranzo, Toshiko Tanaka, Nicholas J. Timpson, Peter Almgren, Amanda Bennett, Richard N. Bergman, Sheila A. Bingham, Lori L. Bonnycastle, Morris Brown, Noel L. P. Burtt, Peter Chines, Lachlan Coin, Francis S. Collins, John M. Connell, Cyrus Cooper, George Davey Smith, Elaine M. Dennison, Parimal Deodhar, Paul Elliott, Michael R. Erdos, Karol Estrada, David M. Evans, Lauren Gianniny, Christian Gieger, Christopher J. Gillson, Giant Consortium, Wellcome Trust Case Control

    Research output: Contribution to journalArticlepeer-review

    1278 Citations (Scopus)

    Abstract

    Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

    Original languageEnglish
    Pages (from-to)25-34
    Number of pages10
    JournalNature Genetics
    Volume41
    Issue number1
    DOIs
    Publication statusPublished - Jan 2009

    Keywords

    • GENOME-WIDE ASSOCIATION
    • CORONARY-ARTERY-DISEASE
    • FTO GENE
    • ALCOHOL DEPENDENCE
    • COMMON VARIANTS
    • NEURITE OUTGROWTH
    • CHILDHOOD OBESITY
    • ADULT OBESITY
    • EXPRESSION
    • MICE

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