Linkage analysis of obesity phenotypes in pre- and post-menopausal women from a United States mid-western population.
Linkage analysis of obesity phenotypes in pre- and post-menopausal women from a United States mid-western population.
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DOI：
10.1186/1471-2350-11-156
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发表时间：
2010-11-09
影响因子：
--
通讯作者：
Vachon CM
中科院分区：
文献类型：
--
作者：
Kelemen LE;Atkinson EJ;de Andrade M;Pankratz VS;Cunningham JM;Wang A;Hilker CA;Couch FJ;Sellers TA;Vachon CM
肥胖有很强的遗传影响，一些变异在女性中的关联性比男性更强。女性在绝经后也更有可能将体重分布在腹部。我们调查了遗传位点是否与绝经状态不同的肥胖相关表型有不同的联系。采用403个微卫星标记对来自90个多代同堂家庭的172名绝经前妇女和405名绝经后妇女的体重指数（BMI）、腰围（WC）、臀围（HC）和腰臀比（WHR）表型进行单变量和双变量连锁分析。双变量分析使用肥胖表型的成对组合来检测遗传相关性状具有多效性效应的位点的连锁。在WC、HC和WHR模型中调整BMI。与绝经后女性相比，绝经前女性的BMI（分别为h2 = 94%和h2 = 39%）和HC（分别为h2 = 99%和h2 = 43%）的遗传率较高，WC（分别为h2 = 29%和h2 = 61%）和WHR（分别为h2 = 39%和h2 = 57%）的遗传率较低。在绝经前女性中，最强的连锁证据是BMI和HC特征在3 p26（双变量LOD = 3.65）和13 q13-q14（双变量LOD = 3.59）的组合。在绝经后女性中，遗传连锁的最高证据水平是HC在4p15.3（单变量LOD = 2.70）和14 q13（单变量LOD = 2.51）。WC与任何位点均无明显连锁。这些结果支持了脂肪沉积的遗传基础，不同的绝经状态，并表明，相同的基因座编码的基因，影响一般肥胖（BMI）和HC，特别是在绝经前妇女。然而，较低的遗传力在绝经前妇女的腰围和腰臀比表明，绝经前腰围可能在更大程度上受可控的环境因素比绝经后腰围。可能的是，针对绝经前妇女体重控制的干预措施可能会预防或减轻绝经后腹部重量沉积。
Obesity has a strong genetic influence, with some variants showing stronger associations among women than men. Women are also more likely to distribute weight in the abdomen following menopause. We investigated whether genetic loci link with obesity-related phenotypes differently by menopausal status. We performed univariate and bivariate linkage analysis for the phenotypes of body mass index (BMI), waist (W) and hip (H) circumferences (WC, HC), and WH ratio (WHR) separately among 172 pre-menopausal and 405 post-menopausal women from 90 multigenerational families using a genome scan with 403 microsatellite markers. Bivariate analysis used pair-wise combinations of obesity phenotypes to detect linkage at loci with pleiotropic effects for genetically correlated traits. BMI was adjusted in models of WC, HC and WHR. Pre-menopausal women, compared to post-menopausal women, had higher heritability for BMI (h2 = 94% versus h2 = 39%, respectively) and for HC (h2 = 99% versus h2 = 43%, respectively), and lower heritability for WC (h2 = 29% versus h2 = 61%, respectively) and for WHR (h2 = 39% versus h2 = 57%, respectively). Among pre-menopausal women, the strongest evidence for linkage was for the combination of BMI and HC traits at 3p26 (bivariate LOD = 3.65) and at 13q13-q14 (bivariate LOD = 3.59). Among post-menopausal women, the highest level of evidence for genetic linkage was for HC at 4p15.3 (univariate LOD = 2.70) and 14q13 (univariate LOD = 2.51). WC was not clearly linked to any locus. These results support a genetic basis for fat deposition that differs by menopausal status, and suggest that the same loci encode genes that influence general obesity (BMI) and HC, specifically, among pre-menopausal women. However, lower heritability among pre-menopausal women for WC and WHR suggests that pre-menopausal waist girth may be influenced to a greater extent by controllable environmental factors than post-menopausal waist girth. Possibly, targeted interventions for weight control among pre-menopausal women may prevent or attenuate post-menopausal abdominal weight deposition.
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影响因子：
120.7
作者：
Flegal, Katherine M.;Carroll, Margaret D.;Curtin, Lester R.
通讯作者：
Curtin, Lester R.
影响因子：
120.7
作者：
Flegal, KM;Carroll, MD;Johnson, CL
通讯作者：
Johnson, CL
影响因子：
4.5
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
通讯作者：
North KE
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：
168.9
作者：
Danaei, G;Vander Hoorn, S;Ezzati, M
通讯作者：
Ezzati, M