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NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.
Tuesday,2012-11-06 12:18 America/Los_Angeles — eenright
| Title | NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Heard-Costa, NL, Zillikens, CM, Monda, KL, Johansson, A, Harris, TB, Fu, M, Haritunians, T, Feitosa, MF, Aspelund, T, Eiriksdottir, G, Garcia, M, Launer, LJ, Smith, AV, Mitchell, BD, McArdle, PF, Shuldiner, AR, Bielinski, SJ, Boerwinkle, E, Brancati, F, Demerath, EW, Pankow, JS, Arnold, AM, Chen, Y-DI, Glazer, NL, McKnight, B, Psaty, BM, Rotter, JI, Amin, N, Campbell, H, Gyllensten, U, Pattaro, C, Pramstaller, PP, Rudan, I, Struchalin, M, Vitart, V, Gao, X, Kraja, A, Province, MA, Zhang, Q, Atwood, LD, Dupuis, J, Hirschhorn, JN, Jaquish, CE, O'Donnell, CJ, Vasan, RS, White, CC, Aulchenko, YS, Estrada, K, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Witteman, JCM, Oostra, BA, Kaplan, RC, Gudnason, V, O'Connell, JR, Borecki, IB, van Duijn, CM, Cupples, AL, Fox, CS, North, KE |
| Journal | PLoS Genet |
| Volume | 5 |
| Issue | 6 |
| Pagination | e1000539 |
| Date Published | 2009 Jun |
| ISSN | 1553-7404 |
| Keywords | Aged, Body Mass Index, Cohort Studies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Nerve Tissue Proteins, Obesity, Polymorphism, Single Nucleotide, Waist Circumference |
| Abstract | <p>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 = 6.4x10(-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 = 5.3x10(-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 = 7.4x10(-6), 0.024 z-score units (0.10 kg/m(2)) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07-1.19; p = 3.2x10(-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.</p> |
| DOI | 10.1371/journal.pgen.1000539 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 19557197 |
| PubMed Central ID | PMC2695005 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States M01-RR00425 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States P30 DK063491-05 / DK / NIDDK NIH HHS / United States R01 AR046838 / AR / NIAMS NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States HSN268200625226C / / PHS HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL72515 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States UL1 RR 025005 / RR / NCRR NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States P30 DK079637 / DK / NIDDK NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 AG18728 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States M01 RR 16500 / RR / NCRR NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01-HC-15103 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01DK06833603 / DK / NIDDK NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States P30 DK063491-039004 / DK / NIDDK NIH HHS / United States U01 HL084756 / HL / NHLBI NIH HHS / United States R01DK07568101 / DK / NIDDK NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States P30 DK072488 / DK / NIDDK NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States U01 HL072515 / HL / NHLBI NIH HHS / United States P30 DK063491-029004 / DK / NIDDK NIH HHS / United States M01 RR016500 / RR / NCRR NIH HHS / United States U01 HL84756 / HL / NHLBI NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States R01HL08770003 / HL / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States P30 DK063491-019004 / DK / NIDDK NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States P30 DK063491-049004 / DK / NIDDK NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 AG018728 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01 HL088119 / HL / NHLBI NIH HHS / United States |