Yu Yi, Wyszynski Diego F, Waterworth Dawn M, Wilton Steven D, Barter Philip J, Kesäniemi Y Antero, Mahley Robert W, McPherson Ruth, Waeber Gérard, Bersot Thomas P, Ma Qianli, Sharma Sanjay S, Montgomery Douglas S, Middleton Lefkos T, Sundseth Scott S, Mooser Vincent, Grundy Scott M, Farrer Lindsay A
Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA, USA.
J Lipid Res. 2005 Oct;46(10):2202-13. doi: 10.1194/jlr.M500137-JLR200. Epub 2005 Aug 1.
We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.
我们采用方差成分连锁分析进行全基因组扫描，以定位影响来自459个具有致动脉粥样硬化血脂异常家族的3071名受试者甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇和总胆固醇（TC）水平的数量性状基因座（QTL）。在11q22的一部分土耳其家族中发现了与TG水平连锁的最显著证据[优势对数比（LOD）=3.34]，以及在17q12处（LOD=3.44）。我们进行了序贯寡基因连锁分析，以检查多个QTL是否共同影响土耳其家族中的TG水平。这些分析揭示了20q13上的位点与11q22表现出强上位效应（条件LOD=3.15），以及7q36上的位点与17q12表现出强上位效应（条件LOD=3.21）。我们还在整个家族组的8p21区域发现了与TG的连锁（LOD=3.08）。对于HDL-C水平，在土耳其家族的15号染色体上发现了连锁证据（LOD=3.05），在整个家族组的5号染色体上发现了连锁证据（LOD=2.83）。在整个家族组的8p23处发现了与TC的QTL连锁（LOD=4.05），在一部分土耳其和地中海家族的5q13处发现了连锁（LOD=3.72）。这些QTL为进一步研究导致这些复杂脂质表型的基因提供了重要线索。这些数据还表明，土耳其人群中TG水平的很大一部分变异是由多个基因座的相互作用所解释的。
