Regional heritability mapping method helps explain missing heritability of blood lipid traits in isolated populations

Single single-nucleotide polymorphism (SNP) genome-wide association studies (SSGWAS) may fail to identify loci with modest effects on a trait. The recently developed regional heritability mapping (RHM) method can potentially identify such loci. In this study, RHM was compared with the SSGWAS for blood lipid traits (high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma concentrations of total cholesterol (TC) and triglycerides (TG)). Data comprised 2246 adults from isolated populations genotyped using ~300 000 SNP arrays. The results were compared with large meta-analyses of these traits for validation. Using RHM, two significant regions affecting HDL on chromosomes 15 and 16 and one affecting LDL on chromosome 19 were identified. These regions covered the most significant SNPs associated with HDL and LDL from the meta-analysis. The chromosome 19 region was identified in our data despite the fact that the most significant SNP in the meta-analysis (or any SNP tagging it) w...

单核苷酸多态性（single-nucleotide polymorphism, SNP）全基因组关联研究（Single SNP Genome-Wide Association Studies, SSGWAS）通常难以识别对性状具有中等效应的基因座。近期研发的区域遗传力定位（regional heritability mapping, RHM）方法则有望识别此类基因座。本研究将RHM方法与SSGWAS应用于血脂性状——包括高密度脂蛋白（high-density lipoprotein, HDL）、低密度脂蛋白（low-density lipoprotein, LDL）、血浆总胆固醇（total cholesterol, TC）浓度与甘油三酯（triglycerides, TG）水平，并开展对比分析。研究数据涵盖2246名来自隔离人群的成人受试者，均采用约30万个SNP芯片完成基因分型。为验证分析结果，将其与上述血脂性状的大型荟萃分析结果进行比对。通过RHM方法，本研究在15号、16号染色体上分别鉴定出2个影响HDL的显著区域，同时在19号染色体上鉴定出1个影响LDL的显著区域。上述区域覆盖了荟萃分析中与HDL和LDL相关的最显著SNPs。尽管荟萃分析中最显著的SNP（或任何与其连锁的标签SNP）……