NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.
NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.
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DOI：
10.1371/journal.pgen.1000539
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发表时间：
2009-06
期刊：
影响因子：
4.5
通讯作者：
North KE
中科院分区：
文献类型：
--
作者：
Heard-Costa NL;Zillikens MC;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 YD;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 JC;Oostra BA;Kaplan RC;Gudnason V;O'Connell JR;Borecki IB;van Duijn CM;Cupples LA;Fox CS;North KE
腹部中央脂肪是糖尿病和心血管疾病的一个重要风险因素。为了确定影响腹部中央脂肪的常见变异，我们对腰围（WC）进行了两阶段的全基因组关联分析。共有三个基因位点达到了全基因组显著水平。在第一阶段，来自八项队列研究的31373名白种人后裔证实了FTO和MC4R的作用，并在神经连接蛋白3基因[NRXN3（rs10146997，p = 6.4×10⁻⁷）]中发现了一个与腰围相关的新位点。在第二阶段，通过将第一阶段的结果与GIANT联盟中38641名参与者的结果相结合，证实了与NRXN3的关联（仅在GIANT中p = 0.009，联合分析p = 5.3×10⁻⁸，n = 70014）。G等位基因每增加一个拷贝，平均腰围增加0.0498个标准差单位（0.65厘米）。这个单核苷酸多态性（SNP）也与体重指数（BMI）相关[p = 7.4×10⁻⁶，G等位基因每增加一个拷贝，增加0.024个标准差单位（0.10千克/平方米）]以及肥胖风险相关（比值比1.13，95%置信区间1.07 - 1.19；G等位基因每增加一个拷贝，p = 3.2×10⁻⁵）。NRXN3基因先前已涉及成瘾和奖赏行为，这进一步证明常见的肥胖形式可能是一种由中枢神经系统介导的疾病。我们的研究结果表明，NRXN3中的常见变异与腰围、体重指数和肥胖相关。
肥胖是全球主要的健康问题。在过去两年中，对被称为单核苷酸多态性（SNP）的DNA标记进行的全基因组关联研究已经确定了两个新的遗传因素，这可能有助于科学家更好地理解为什么有些人可能更容易肥胖。同样，本文描述了一项针对肥胖易感基因的大规模全基因组关联分析的结果，该分析包括来自8项独立研究的31373个人。我们发现了一个影响腰围的新基因，即神经连接蛋白3基因（NRXN3），它先前已在成瘾和奖赏行为的研究中被涉及。这些发现进一步证明我们的基因可能影响我们对食物的欲望和摄取，进而影响我们对肥胖的易感性。
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. 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.
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影响因子：
158.5
作者：
Cecil, Joanne E.;Tavendale, Roger;Palmer, Colin N. A.
通讯作者：
Palmer, Colin N. A.
影响因子：
30.8
作者：
Chambers, John C.;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
影响因子：
3.5
作者：
Lachman, Herbert M.;Fann, Cathy S. J.;Knowles, James A.
通讯作者：
Knowles, James A.
影响因子：
7.1
作者：
Lyon, HN;Hirschhorn, JN
通讯作者：
Hirschhorn, JN
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ