Genome scan for human obesity and linkage to markers in 20q13
Genome scan for human obesity and linkage to markers in 20q13
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DOI：
10.1086/302195
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发表时间：
1999-01-01
影响因子：
9.8
通讯作者：
Price, RA
中科院分区：
文献类型：
--
作者：
Lee, JH;Reed, DR;Price, RA
肥胖是一种高度流行的多基因性状，可预测发病率和死亡率的增加。在这里，我们报告的结果，从基因组扫描的基础上354标记在513个成员的92个核心家庭确定通过极端肥胖和正常体重。平均标记间隔与10 cM相似。我们检查了四种相关的肥胖表型，包括通过生物电阻抗评估的体重指数（BMI）（既作为定量诱饵，也作为BMI大于或等于30 kg/m2的阈值的离散特征）和脂肪百分比（既作为定量诱饵，也作为阈值为40%的离散特征）。在基因组扫描的初始阶段，20 q中的四个标记给出了连锁的阳性证据，这在大多数肥胖表型和分析方法中是一致的。饱和后20 q与额外的标记（共25个标记）的扩增样本：713名成员从124个家庭，我们发现连锁的几个标记在一个区域，20 q13，以前牵连在人类和动物研究。对于单点分析，20 q13中的三个标志物（D20 S107、D20 S211和D20 S149）的经验P值（基于蒙特卡罗模拟，其控制了多重检验）小于或等于0.01。此外，D20 S476的参数、仅受影响分析得出的LOD评分为3.06（P =.00009），受影响同胞对检验得出的LOD评分为3.17（P =.000067）。多点分析进一步强化和定位了这些发现，该区域包括几个可能的肥胖候选基因。我们的研究结果表明，一个或多个影响肥胖的基因位于20 q13。
Obesity is a highly prevalent, multigenic trait that predicts increased morbidity and mortality. Here we report results from a genome scan based on 354 markers in 513 members of 92 nuclear families ascertained through extreme obesity and normal body weight. The average marker interval was similar to 10 cM. We examined four correlated obesity phenotypes, including the body-mass index (BMI) (both as a quantitative bait and as a discrete trait with a threshold of BMI greater than or equal to 30 kg/m(2)) and percentage of fat (both as a quantitative bait and as a discrete trait with a threshold of 40%) as assessed by bioelectrical impedance. In the initial stage of the genome scan, four markers in 20q gave positive evidence for linkage, which was consistent across most obesity phenotypes and analytic methods. After saturating 20q with additional markers (25 markers total) in an augmented sample of: 713 members from 124 families, we found linkage to several markers in a region, 20q13, previously implicated in both human and animal studies. Three markers (D20S107, D20S211, and D20S149) in 20q13 had empirical P values (based on Monte Carlo simulations, which controlled for multiple testing) less than or equal to.01 for single-point analysis. In addition, the parametric, affecteds-only analysis for D20S476 yielded a LOD score of 3.06 (P =.00009), and the affected-sib-pair test yielded a LOD score of 3.17 (P =.000067). Multipoint analyses further strengthened and localized these findings, This region includes several plausible candidate genes for obesity. Our results suggest that one or more genes affecting obesity are located in 20q13.