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    NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium

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    pgen.1000539.pdf (200.3Kb)
    Date Issued
    2009-6-26
    Related DOI
    10.1371/journal.pgen.1000539
    Author
    Heard-Costa, Nancy L.
    Zillikens, M. Carola
    Monda, Keri L.
    Johansson, Åsa
    Harris, Tamara B.
    Fu, Mao
    Haritunians, Talin
    Feitosa, Mary F.
    Aspelund, Thor
    Eiriksdottir, Gudny
    Garcia, Melissa
    Launer, Lenore J.
    Smith, Albert V.
    Mitchell, Braxton D.
    McArdle, Patrick F.
    Shuldiner, Alan R.
    Bielinski, Suzette J.
    Boerwinkle, Eric
    Brancati, Fred
    Demerath, Ellen W.
    Pankow, James S.
    Arnold, Alice M.
    Chen, Yii-Der Ida
    Glazer, Nicole L.
    McKnight, Barbara
    Psaty, Bruce M.
    Rotter, Jerome I.
    Amin, Najaf
    Campbell, Harry
    Gyllensten, Ulf
    Pattaro, Cristian
    Pramstaller, Peter P.
    Rudan, Igor
    Struchalin, Maksim
    Vitart, Veronique
    Gao, Xiaoyi
    Kraja, Aldi
    Province, Michael A.
    Zhang, Qunyuan
    Atwood, Larry D.
    Dupuis, Josée
    Hirschhorn, Joel N.
    Jaquish, Cashell E.
    O'Donnell, Christopher J.
    Vasan, Ramachandran S.
    White, Charles C.
    Aulchenko, Yurii S.
    Estrada, Karol
    Hofman, Albert
    Rivadeneira, Fernando
    Uitterlinden, André G.
    Witteman, Jacqueline C. M.
    Oostra, Ben A.
    Kaplan, Robert C.
    Gudnason, Vilmundur
    O'Connell, Jeffrey R.
    Borecki, Ingrid B.
    Van Duijn, Cornelia M.
    Cupples, L. Adrienne
    Fox, Caroline S.
    North, Kari E.
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    Permanent Link
    https://hdl.handle.net/2144/2962
    Citation
    Heard-Costa, Nancy L., M. Carola Zillikens, Keri L. Monda, Åsa Johansson, Tamara B. Harris, Mao Fu, Talin Haritunians, Mary F. Feitosa, Thor Aspelund, Gudny Eiriksdottir, Melissa Garcia, Lenore J. Launer, Albert V. Smith, Braxton D. Mitchell, Patrick F. McArdle, Alan R. Shuldiner, Suzette J. Bielinski, Eric Boerwinkle, Fred Brancati, Ellen W. Demerath, James S. Pankow, Alice M. Arnold, Yii-Der Ida Chen, Nicole L. Glazer, Barbara McKnight, Bruce M. Psaty, Jerome I. Rotter, Najaf Amin, Harry Campbell, Ulf Gyllensten, Cristian Pattaro, Peter P. Pramstaller, Igor Rudan, Maksim Struchalin, Veronique Vitart, Xiaoyi Gao, Aldi Kraja, Michael A. Province, Qunyuan Zhang, Larry D. Atwood, Josée Dupuis, Joel N. Hirschhorn, Cashell E. Jaquish, Christopher J. O'Donnell, Ramachandran S. Vasan, Charles C. White, Yurii S. Aulchenko, Karol Estrada, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Jacqueline C. M. Witteman, Ben A. Oostra, Robert C. Kaplan, Vilmundur Gudnason, Jeffrey R. O'Connell, Ingrid B. Borecki, Cornelia M. van Duijn, L. Adrienne Cupples, Caroline S. Fox, Kari E. North. "NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium" PLoS Genetics5(6):e1000539. (2009)
    Abstract
    Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity. Author Summary Obesity is a major health concern worldwide. In the past two years, genome-wide association studies of DNA markers known as SNPs (single nucleotide polymorphisms) have identified two novel genetic factors that may help scientists better understand why some people may be more susceptible to obesity. Similarly, this paper describes results from a large scale genome-wide association analysis for obesity susceptibility genes that includes 31,373 individuals from 8 separate studies. We uncovered a new gene influencing waist circumference, the neurexin 3 gene (NRXN3), which has been previously implicated in studies of addiction and reward behavior. These findings lend further evidence that our genes may influence our desire and consumption of food and, in turn, our susceptibility to obesity.
    Collections
    • MED: Medicine Papers [229]
    • Framingham Heart Study Papers [52]
    • MED: Neurology Papers [66]
    • SPH Biostatistics Papers [122]

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