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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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dc.contributor.author Heard-Costa, Nancy L. en_US
dc.contributor.author Zillikens, M. Carola en_US
dc.contributor.author Monda, Keri L. en_US
dc.contributor.author Johansson, Åsa en_US
dc.contributor.author Harris, Tamara B. en_US
dc.contributor.author Fu, Mao en_US
dc.contributor.author Haritunians, Talin en_US
dc.contributor.author Feitosa, Mary F. en_US
dc.contributor.author Aspelund, Thor en_US
dc.contributor.author Eiriksdottir, Gudny en_US
dc.contributor.author Garcia, Melissa en_US
dc.contributor.author Launer, Lenore J. en_US
dc.contributor.author Smith, Albert V. en_US
dc.contributor.author Mitchell, Braxton D. en_US
dc.contributor.author McArdle, Patrick F. en_US
dc.contributor.author Shuldiner, Alan R. en_US
dc.contributor.author Bielinski, Suzette J. en_US
dc.contributor.author Boerwinkle, Eric en_US
dc.contributor.author Brancati, Fred en_US
dc.contributor.author Demerath, Ellen W. en_US
dc.contributor.author Pankow, James S. en_US
dc.contributor.author Arnold, Alice M. en_US
dc.contributor.author Chen, Yii-Der Ida en_US
dc.contributor.author Glazer, Nicole L. en_US
dc.contributor.author McKnight, Barbara en_US
dc.contributor.author Psaty, Bruce M. en_US
dc.contributor.author Rotter, Jerome I. en_US
dc.contributor.author Amin, Najaf en_US
dc.contributor.author Campbell, Harry en_US
dc.contributor.author Gyllensten, Ulf en_US
dc.contributor.author Pattaro, Cristian en_US
dc.contributor.author Pramstaller, Peter P. en_US
dc.contributor.author Rudan, Igor en_US
dc.contributor.author Struchalin, Maksim en_US
dc.contributor.author Vitart, Veronique en_US
dc.contributor.author Gao, Xiaoyi en_US
dc.contributor.author Kraja, Aldi en_US
dc.contributor.author Province, Michael A. en_US
dc.contributor.author Zhang, Qunyuan en_US
dc.contributor.author Atwood, Larry D. en_US
dc.contributor.author Dupuis, Josée en_US
dc.contributor.author Hirschhorn, Joel N. en_US
dc.contributor.author Jaquish, Cashell E. en_US
dc.contributor.author O'Donnell, Christopher J. en_US
dc.contributor.author Vasan, Ramachandran S. en_US
dc.contributor.author White, Charles C. en_US
dc.contributor.author Aulchenko, Yurii S. en_US
dc.contributor.author Estrada, Karol en_US
dc.contributor.author Hofman, Albert en_US
dc.contributor.author Rivadeneira, Fernando en_US
dc.contributor.author Uitterlinden, André G. en_US
dc.contributor.author Witteman, Jacqueline C. M. en_US
dc.contributor.author Oostra, Ben A. en_US
dc.contributor.author Kaplan, Robert C. en_US
dc.contributor.author Gudnason, Vilmundur en_US
dc.contributor.author O'Connell, Jeffrey R. en_US
dc.contributor.author Borecki, Ingrid B. en_US
dc.contributor.author van Duijn, Cornelia M. en_US
dc.contributor.author Cupples, L. Adrienne en_US
dc.contributor.author Fox, Caroline S. en_US
dc.contributor.author North, Kari E. en_US
dc.date.accessioned 2012-01-09T21:00:17Z
dc.date.available 2012-01-09T21:00:17Z
dc.date.issued 2009-6-26 en_US
dc.identifier.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) en_US
dc.identifier.issn 1553-7404 en_US
dc.identifier.uri http://hdl.handle.net/2144/2962
dc.description.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. en_US
dc.description.sponsorship National Institues of Health (N01-AG-12100, HHSN268200625226C, UL1RR025005); NIA Intramural Research Program; Althingi; National Institute on Aging; National Heart, Lung, and Blood Institute (N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, R01HL08770003, U01 HL080295, R01 HL087652); National Human Genome Research Institute (U01HG004402); National Center for Research Resources (UL1 RR 025005); National Institutes of Health (NIH) and NIH Roadmap for Medical Research (N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133); National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; Cedars-Sinai Board of Governors' Chair in Medical Genetics; Cedars-Sinai General Clinical Research Center (M01-RR00425); National Institues of Diabetes and Digestive and Kidney Diseases (DK063491, R01DK06833603, R01DK07568101) Affymetrix genotyping was supported by contract N02-HL-6-4278, U01 HL84756, U01 HL72515, R01 AG18728, R01 AR046838, R01 HL088119, NIH P30 DK072488); University of Maryland General Clinical Research Center (M01 RR 16500); Department of Veterans Affairs; Veterans Affairs Medical Center Baltimore Geriatric Research; Education and Clinical Center (GRECC); Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry of Education, Culture, and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam; Netherlands Organization for Scientific Research (175.010.2005.011, 911.03.012); Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (050-060-810); European Commission FP6 STRP (018947, LSHG-CT-2006-01947); Ministry of Health of the Autonomous Province of Bolzano and the South Tyrolean Sparkasse Foundation; Netherlands Organization for Scientific Research (91203014); Russian Foundation for Basic Research (NWO-RFBR, 047.017.043); Center of Medical Systems Biology; Medical Research Council UK to H.C., A.F.W. and I.R.; and Ministry of Science, Education and Sport of the Republic of Croatia (108-1080315-0302) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pgen.1000539 en_US
dc.identifier.pubmedid 19557197 en_US
dc.identifier.pmcid 2695005 en_US


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