A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program.
A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program.
复制标题
DOI：
10.1086/340362
复制
发表时间：
2002-05
影响因子：
9.8
通讯作者：
Xiaodong Wu;R. Cooper;I. Borecki;C. Hanis;M. Bray;C. Lewis;Xiaofeng Zhu-;Donghui Kan;A. Luke;David Curb
中科院分区：
文献类型：
--
作者：
Xiaodong Wu;R. Cooper;I. Borecki;C. Hanis;M. Bray;C. Lewis;Xiaofeng Zhu-;Donghui Kan;A. Luke;David Curb
肥胖基因组扫描的综合分析是利用国家心脏、肺和血液研究所家庭血压项目的中期结果进行的。在这个研究项目中，四个多中心的研究者网络进行了八项单独的研究。数据来自四个种族群体（白色，黑人，墨西哥裔美国人和亚洲人）的6,849人。该样本代表了已分析肥胖症的全基因组扫描数据的最大单个集合，并提供了对复杂表型的连锁分析的再现性的测试。体重指数（BMI）被用作肥胖的衡量标准。首先，通过使用方差分量法，在四个网络中的八个种族中的每一个中分别进行全基因组连锁分析。在个体研究的分析中，只有一个区域显示出与BMI的显著关联：3q22.1（对于GENOA网络黑色样本，LOD 3.45）。另外发现了6个相关LOD >2的区域，包括3p24.1、7p15.2、7q22.3、14q24.3、16q12.2和17p11.2。在这些发现中，7p15.2，7q22.3和17p11.2的连锁已在其他地方报道。然后使用修改的Fisher综合程序来联合收割机组合来自八个基因组扫描中的每一个的P值。对荟萃分析进行了补充，结合了白人、黑人和墨西哥裔美国人的平均等位基因共享身份（pi）。使用这种方法，我们发现了3q 27处数量性状基因座的强有力连锁证据（标记D3 S2427; LOD 3.40，P= 0.03）。至少在另外两项研究中，同一位置已被证明与肥胖相关的特征和糖尿病有关。这些结果（1）证实了先前报道的3号、7号和17号染色体上的肥胖易感基因座，（2）表明，只要相同的基因在所有考虑的样本中都有影响，那么将不同研究的样本结合起来可以提高检测具有小到中等影响的共同基因的能力。
A combined analysis of genome scans for obesity was undertaken using the interim results from the National Heart, Lung, and Blood Institute Family Blood Pressure Program. In this research project, four multicenter networks of investigators conducted eight individual studies. Data were available on 6,849 individuals from four ethnic groups (white, black, Mexican American, and Asian). The sample represents the largest single collection of genomewide scan data that has been analyzed for obesity and provides a test of the reproducibility of linkage analysis for a complex phenotype. Body mass index (BMI) was used as the measure of adiposity. Genomewide linkage analyses were first performed separately in each of the eight ethnic groups in the four networks, through use of the variance-component method. Only one region in the analyses of the individual studies showed significant linkage with BMI: 3q22.1 (LOD 3.45, for the GENOA network black sample). Six additional regions were found with an associated LOD >2, including 3p24.1, 7p15.2, 7q22.3, 14q24.3, 16q12.2, and 17p11.2. Among these findings, the linkage at 7p15.2, 7q22.3, and 17p11.2 has been reported elsewhere. A modified Fisher's omnibus procedure was then used to combine the P values from each of the eight genome scans. A complimentary approach to the meta-analysis was undertaken, combining the average allele-sharing identity by descent (pi) for whites, blacks, and Mexican Americans. Using this approach, we found strong linkage evidence for a quantitative-trait locus at 3q27 (marker D3S2427; LOD 3.40, P=.03). The same location has been shown to be linked with obesity-related traits and diabetes in at least two other studies. These results (1) confirm the previously reported obesity-susceptibility locus on chromosomes 3, 7, and 17 and (2) demonstrate that combining samples from different studies can increase the power to detect common genes with a small-to-moderate effect, so long as the same gene has an effect in all samples considered.