Zintzaras Elias, Kitsios Georgios
Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, 41222, Larissa, Greece.
J Hum Genet. 2006;51(11):1015-1021. doi: 10.1007/s10038-006-0053-x. Epub 2006 Sep 22.
Myocardial infarction (MI) is a complication of coronary artery disease and the leading cause of death in the Western world. MI is considered a distinct phenotype with an increased genetic component for its premature type. MI's exact inheritance pattern is still unknown. Genome searches for identifying susceptibility loci for premature MI produced inconclusive or inconsistent results. Thus, a genome search meta-analysis (GSMA) was applied to available genome search data on premature MI. GSMA is a non-parametric method to identify genetic regions that rank high, on average in terms of linkage statistics across genome searches unweighted or weighted by study size. The significance of each region's average and heterogeneity, unadjusted or adjusted by neighbouring average simulated ranks, was calculated using a Monte Carlo test. The meta-analysis involved five genome searches in Caucasians. Eight regions (6p22.3-6p21.1, 14p13-14q13.1, 13q33.1-13q34, 5p15.33-5p15.1, 8q13.2-8q22.2, 1p36.21-1p35.2, 12q24.31-12q24.33, 8q24.21-8q24.3) were found to have significant average rank by either unweighted or weighted analyses. In addition, region 8q24.21-8q24.3 produced significant low heterogeneity (P (unadjusted)=0.03 and P (adjusted)=0.05). Four regions (6p22.3-6p21.1, 14p13-14q13.1, 8q13.2-8q22.2, 8q24.21-8q24.3) were not identified by the individual studies. The meta-analysis suggests that these four regions should be further investigated for genes that confer susceptibility to MI.
心肌梗死（MI）是冠状动脉疾病的一种并发症，也是西方世界主要的死亡原因。MI被认为是一种独特的表型，其早发型具有增加的遗传成分。MI的确切遗传模式仍然未知。针对早发型MI进行的全基因组搜索以确定易感基因座，结果并不确定或不一致。因此，将全基因组搜索荟萃分析（GSMA）应用于早发型MI的现有全基因组搜索数据。GSMA是一种非参数方法，用于识别在未加权或按研究规模加权的全基因组搜索中，连锁统计平均排名较高的遗传区域。使用蒙特卡罗检验计算每个区域的平均值和异质性的显著性，未调整或通过相邻平均模拟排名进行调整。该荟萃分析涉及对白种人的五项全基因组搜索。通过未加权或加权分析发现八个区域（6p22.3 - 6p21.1、14p13 - 14q13.1、13q33.1 - 13q34、5p15.33 - 5p15.1、8q13.2 - 8q22.2、1p36.21 - 1p35.2、12q24.31 - 12q24.33、8q24.21 - 8q24.3）具有显著的平均排名。此外，区域8q24.21 - 8q24.3产生了显著的低异质性（P（未调整）=0.03，P（调整）=0.05）。四项单独研究未识别出四个区域（6p22.3 - 6p21.1、14p13 - 14q13.1、8q13.2 - 8q22.2、8q24.21 - 8q24.3）。该荟萃分析表明，应进一步研究这四个区域中赋予MI易感性的基因。
