Wu Xiaodong, Cooper Richard S, Borecki Ingrid, Hanis Craig, Bray Molly, Lewis Cora E, Zhu Xiaofeng, Kan Donghui, Luke Amy, Curb David
Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL 60153, USA.
Am J Hum Genet. 2002 May;70(5):1247-56. doi: 10.1086/340362. Epub 2002 Mar 28.
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.
利用美国国立心肺血液研究所家庭血压项目的中期结果，对肥胖症的全基因组扫描进行了综合分析。在这个研究项目中，四个多中心研究团队开展了八项独立研究。研究数据来自四个种族群体（白人、黑人、墨西哥裔美国人及亚裔）的6849名个体。该样本是针对肥胖症进行分析的最大规模的全基因组扫描数据单一集合，为复杂表型的连锁分析的可重复性提供了检验。体重指数（BMI）被用作肥胖程度的衡量指标。全基因组连锁分析首先通过方差成分法在四个研究团队中的八个种族群体中分别进行。在各独立研究的分析中，只有一个区域显示出与BMI存在显著连锁：3q22.1（在热那亚研究团队的黑人样本中，LOD为3.45）。另外还发现了六个LOD>2的相关区域，包括3p24.1、7p15.2、7q22.3、14q24.3、16q12.2和17p11.2。在这些研究结果中，7p15.2、7q22.3和17p11.2的连锁情况在其他地方已有报道。然后使用改良的Fisher综合检验法对八项全基因组扫描的P值进行合并。采用了一种与荟萃分析互补的方法，将白人、黑人和墨西哥裔美国人的平均同源等位基因共享度（pi）进行合并。通过这种方法，我们在3q27（标记D3S2427；LOD 3.40，P = 0.03）发现了一个数量性状位点的强连锁证据。在至少另外两项研究中，相同位置已被证明与肥胖相关性状及糖尿病存在连锁关系。这些结果（1）证实了先前报道的位于3号、7号和17号染色体上的肥胖易感位点，并且（2）表明合并来自不同研究的样本能够提高检测具有中、小效应的常见基因的效能，只要同一基因在所有纳入考虑的样本中都有作用。
