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

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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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Title: NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium
Author: Heard-Costa, Nancy L.; Zillikens, M. Carola; Monda, Keri L.; 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; Jaquish, Cashell E.; Vasan, Ramachandran S.; White, Charles C.; Aulchenko, Yurii S.; Estrada, Karol; Rivadeneira, Fernando; Uitterlinden, André G.; Witteman, Jacqueline C. M.; Oostra, Ben A.; Gudnason, Vilmundur; O'Connell, Jeffrey R.; Borecki, Ingrid B.; van Duijn, Cornelia M.; Cupples, L. Adrienne; North, Kari E.; Hirschhorn, Joel Naom; O'Donnell, Christopher Joseph; Hofman, Albert; Kaplan, Robert C.; Fox, Caroline; Johansson, Asa

Note: Order does not necessarily reflect citation order of authors.

Citation: Heard-Costa, Nancy L., M. Carola Zillikens, Keri L. Monda, Asa Johansson, Tamara B. Harris, Mao Fu, Talin Haritunians, et. al. 2009. NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium. PLoS Genetics 5(6): e1000539.
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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.
Published Version: doi://10.1371/journal.pgen.1000539
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695005/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4739277

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