Premature myocardial infarction novel susceptibility locus on chromosome 1P34-36 identified by genomewide linkage analysis
Premature myocardial infarction novel susceptibility locus on chromosome 1P34-36 identified by genomewide linkage analysis
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DOI：
10.1086/381560
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发表时间：
2004-02-01
影响因子：
9.8
通讯作者：
Topol, EJ
中科院分区：
文献类型：
--
作者：
Wang, Q;Rao, SQ;Topol, EJ
在西方世界，最常见的死亡和残疾原因是动脉粥样硬化性冠状动脉疾病（CAD）和急性心肌梗死（MI）。这种常见疾病被认为具有多基因基础，与环境因素有复杂的相互作用。在这里，我们报告了在一个特征明确的美国人中进行的全基因组MI易感基因搜索的结果。S.队列包括428个家族性早发CAD和MI多发性家族的1，613名个体：712名MI，974名CAD，平均发病年龄为44.4 ± 9.7岁。基因分型是在国家心脏、肺和血液研究所哺乳动物基因分型设施通过使用跨越整个人类基因组每10 cM的408个标记进行的。用改良的Haseman-Elston回归模型进行连锁分析。进行了三次全基因组扫描：单点、多点和仅对白色家系（队列的92%）进行的多点扫描。在染色体1 p34 -36区域检测到一个新的MI显著易感位点，其多点等位基因共享P值小于或等于10（-12）（LOD=11.68）。通过使用排列检验进行验证，在该位点产生了.00011的逐点经验P值，这对应于P的全基因组显著性。
The most frequent causes of death and disability in the Western world are atherosclerotic coronary artery disease (CAD) and acute myocardial infarction (MI). This common disease is thought to have a polygenic basis with a complex interaction with environmental factors. Here, we report results of a genomewide search for susceptibility genes for MI in a well-characterized U. S. cohort consisting of 1,613 individuals in 428 multiplex families with familial premature CAD and MI: 712 with MI, 974 with CAD, and average age of onset of 44.4+/-9.7 years. Genotyping was performed at the National Heart, Lung, and Blood Institute Mammalian Genotyping Facility through use of 408 markers that span the entire human genome every 10 cM. Linkage analysis was performed with the modified Haseman-Elston regression model through use of the SIBPAL program. Three genomewide scans were conducted: single-point, multipoint, and multipoint performed on of white pedigrees only (92% of the cohort). One novel significant susceptibility locus was detected for MI on chromosomal region 1p34-36, with a multipoint allele-sharing P value of less than or equal to10(-12) (LOD=11.68). Validation by use of a permutation test yielded a pointwise empirical P value of .00011 at this locus, which corresponds to a genomewide significance of P