Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol
Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol
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DOI：
10.1093/hmg/ddh119
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发表时间：
2004-05-15
影响因子：
3.5
通讯作者：
Reich, JG
中科院分区：
文献类型：
--
作者：
Knoblauch, H;Bauerfeind, A;Reich, JG
单核苷酸多态(SNPs)和多基因衍生的单倍型可以解释复杂性状的遗传差异；然而，这一假说尚未得到严格的检验。在早期的一项研究中，我们分析了6个基因，现在扩大到包括13个基因。我们研究了250个家庭，1054个个体，并测量了血脂表型。我们重点研究了低密度胆固醇(LDL)、高密度胆固醇(HDL)及其比值(LDL/HDL)。根据标准遗传模型对表型变异的成分分析表明，低密度脂蛋白的遗传变异占总变异的26%，高密度脂蛋白的遗传变异解释38%，低密度脂蛋白/高密度脂蛋白的遗传变异解释28%。对13个血脂相关基因的93个SNPs进行基因分型，共产生230种单倍型。所有被测基因中单倍型的关联解释了遗传表型变异的主要部分。对于低密度脂蛋白，与单倍型的关联解释了67%，对于高密度脂蛋白，解释了相对于多基因背景的遗传差异的58%。我们的结论是，这些单倍型解释了这些代表性德国家系中低密度脂蛋白、高密度脂蛋白和低密度脂蛋白/高密度脂蛋白的大部分遗传差异。对每个座位遗传变异的贡献率分析表明，APOE(50%)、CETP(28%)、LIPC(9%)、APOB(8%)和LDLR(5%)影响低密度脂蛋白(LDL)的变异。LIPC(53%)、CETP(25%)、ABCA1(10%)、LPL(6%)和LDLR(6%)影响高密度脂蛋白的变异。低密度脂蛋白/高密度脂蛋白比值主要受APOE(36%)、CETP(27%)和LIPC(31%)的影响。这种扩展的分析大大增加了对这些复杂性状的遗传变异的解释。
Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed six genes and have now expanded this investigation to include 13. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL), high-density cholesterol (HDL) and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model` showed that the genetic variance on LDL explained 26%, on HDL explained 38% and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%) and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%) and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%) and LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.