Study of exonic variation identifies incremental information regarding lipid-related and coronary heart disease genes.
Study of exonic variation identifies incremental information regarding lipid-related and coronary heart disease genes.
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外显子变异的研究确定了有关脂质相关和冠心病基因的增量信息。
DOI：
10.1161/circresaha.114.304693
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发表时间：
2014
影响因子：
20.1
通讯作者：
Quertermous,Thomas
中科院分区：
文献类型：
--
作者：
Assimes,ThemistoclesL;Quertermous,Thomas
Assimes 和 Quertermous 鉴定了 CHD 479 中的致病基因，11 个基因中的总共 16 个变异达到了全基因组显着性。其中大多数映射到已知的脂质位点，其中因果基因没有模糊性。然而，2 个映射到的基因（RNF111 和 TM6SF2）此前并未明确与血脂水平相关。重要的是，这些变体中只有 2 个的次要等位基因频率 < 1%，只有 3 个变体的次要等位基因频率 < 2%。 9 个已建立的脂质位点内的全基因组显着变异揭示了与相应 GWAS 索引 SNP 的一系列大部分可预测的关系。 7 在某些位点，外显子变异被发现与 GWAS 索引 SNP 相同或在统计学上无法区分（例如 APOB 变异和 LDL、LPL 变异和甘油三酯）。在其他位点，外显子 SNP 充当独立于 GWAS 索引 SNP 的额外强信号（例如 ABCG5/ABCG8 变体和 LDL、
Assimes and Quertermous Identification of a Causal Gene in CHD 479 a total of 16 variants in 11 genes reached genome-wide significance. Most of these mapped to known lipid loci where there is no ambiguity of the causal gene. However, 2 mapped to genes (RNF111 and TM6SF2) that have not been previously clearly implicated in blood lipid levels. Importantly, only 2 of these variants had a minor allele frequency< 1%, and only 3 had a minor allele frequency< 2%. The genome-wide significant variants within the 9 established lipid loci revealed a range of mostly predictable relationships to the corresponding GWAS index SNPs. 7 At some loci, the exonic variant was found to be either identical or statistically indistinguishable to the GWAS index SNP (eg, APOB variant and LDL, LPL variant and triglycerides). At other loci, the exonic SNPs served as additional strong signals independent of the GWAS index SNPs (eg, ABCG5/ABCG8 variants and LDL,