Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish
Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish
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DOI：
10.1159/000103630
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发表时间：
2007-01-01
期刊：
影响因子：
1.8
通讯作者：
Shuldiner, Alan R.
中科院分区：
文献类型：
--
作者：
Post, Wendy;Shen, Haiqing;Shuldiner, Alan R.
背景资料：通过全基因组关联研究，我们发现心电图QT间期与NOS 1AP（CAPON）基因多态性相关。本研究的目的是在旧秩序阿米什人中复制这种关联。方法：选择4个NOS 1AP单核苷酸多态性位点（SNPs），在感兴趣区域（类似于120 kb片段）捕获所有主要单倍型。在遗传和表型干预（HAPI）心脏研究的763例受试者中完成了基因分型。使用方差分量法进行关联分析，考虑个体的相关性。结果：QT间期的遗传度为0.50 +/- 0.09（p = 1.9 x 10（-9））。所有四种SNP都是常见的，SNP之间具有高度相关性。四个SNPs中的两个（成对r（2）= 0.86）与校正QT间期的变化显著相关（rs 1415262，p = 0.02和rs 10494366，p = 0.006，两者的加性模型）。SNP rs 10494366解释了0.9%的QT间期变异性，平均遗传效应为6.1 ms。包含rs 10494366次要等位基因的单倍型与较长的QT间期相关。结论：这项研究提供了进一步的证据表明，NOS 1AP变异影响QT间期，并进一步验证了全基因组关联研究的实用性，这是一种相对较新的基因发现方法。版权所有（c）2007 S. Karger AG，巴塞尔
Background: Through a genome-wide association study, we discovered an association of the electrocardiographic QT interval with polymorphisms in the NOS1AP ( CAPON) gene. The purpose of the current study was to replicate this association in the Old Order Amish. Methods: Four NOS1AP SNPs were selected that captured all major haplotypes in the region of interest (similar to 120 kb segment). Genotyping was completed in 763 subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study. Association analyses were performed using a variance components methodology, accounting for relatedness of individuals. Results: Heritability of the QT interval was 0.50 +/- 0.09 (p = 1.9 x 10(-9)). All four SNPs were common with a high degree of correlation between SNPs. Two of the four SNPs (pairwise r(2) = 0.86) were significantly associated with variation in adjusted QT interval (rs1415262, p = 0.02 and rs10494366, p = 0.006, additive models for both). SNP rs10494366 explained 0.9% of QT interval variability, with an average genetic effect of 6.1 ms. Haplotypes that contained the minor allele for rs10494366 were associated with longer QT interval. Conclusions: This study provides further evidence that NOS1AP variants influence QT interval and further validates the utility of genome-wide association studies, a relatively new approach to gene discovery. Copyright (c) 2007 S. Karger AG, Basel