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


Show simple item record Heard-Costa, Nancy L. en_US Zillikens, M. Carola en_US Monda, Keri L. en_US Johansson, Åsa en_US Harris, Tamara B. en_US Fu, Mao en_US Haritunians, Talin en_US Feitosa, Mary F. en_US Aspelund, Thor en_US Eiriksdottir, Gudny en_US Garcia, Melissa en_US Launer, Lenore J. en_US Smith, Albert V. en_US Mitchell, Braxton D. en_US McArdle, Patrick F. en_US Shuldiner, Alan R. en_US Bielinski, Suzette J. en_US Boerwinkle, Eric en_US Brancati, Fred en_US Demerath, Ellen W. en_US Pankow, James S. en_US Arnold, Alice M. en_US Chen, Yii-Der Ida en_US Glazer, Nicole L. en_US McKnight, Barbara en_US Psaty, Bruce M. en_US Rotter, Jerome I. en_US Amin, Najaf en_US Campbell, Harry en_US Gyllensten, Ulf en_US Pattaro, Cristian en_US Pramstaller, Peter P. en_US Rudan, Igor en_US Struchalin, Maksim en_US Vitart, Veronique en_US Gao, Xiaoyi en_US Kraja, Aldi en_US Province, Michael A. en_US Zhang, Qunyuan en_US Atwood, Larry D. en_US Dupuis, Josée en_US Hirschhorn, Joel N. en_US Jaquish, Cashell E. en_US O'Donnell, Christopher J. en_US Vasan, Ramachandran S. en_US White, Charles C. en_US Aulchenko, Yurii S. en_US Estrada, Karol en_US Hofman, Albert en_US Rivadeneira, Fernando en_US Uitterlinden, André G. en_US Witteman, Jacqueline C. M. en_US Oostra, Ben A. en_US Kaplan, Robert C. en_US Gudnason, Vilmundur en_US O'Connell, Jeffrey R. en_US Borecki, Ingrid B. en_US van Duijn, Cornelia M. en_US Cupples, L. Adrienne en_US Fox, Caroline S. en_US North, Kari E. en_US 2012-01-09T21:00:17Z 2012-01-09T21:00:17Z 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.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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