Genome-wide scan for blood pressure suggests linkage to chromosome 11, and replication of loci on 16, 17, and 22
Genome-wide scan for blood pressure suggests linkage to chromosome 11, and replication of loci on 16, 17, and 22
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DOI：
10.1161/01.hyp.0000148994.89903.fa
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发表时间：
2004-12-01
期刊：
影响因子：
8.3
通讯作者：
Andrew, T
中科院分区：
文献类型：
--
作者：
de Lange, M;Spector, TD;Andrew, T
高血压是最早被研究的复杂性状之一，被认为受到多基因和多种环境危险因素的影响。一些基因组研究已经发现了血压或原发性高血压的比值对数（LOD）分数，但很少有位点被复制。在这项研究中，我们对来自伦敦TwinsUK登记处的1109对白色女性双卵双胞胎进行了收缩压（SBP）和舒张压（DBP）的全基因组连锁分析。多点连锁分析复制了3个先前报告的连锁峰的位置：在染色体16上65 cM（SBP LOD 0.8和DBP LOD 1.8）;在染色体17上70 cM（SBP LOD 1.8）;和在染色体22上35 cM（SBP LOD 0.97和DBP LOD 0.99）。多点分析的结果显示，在11号染色体上35 cM处存在1个新的提示性SBP连锁（多点LOD 2.28; 2点P=0.0007）。当排除血压药物时，结果相似。这些结果对于高血压研究来说是令人鼓舞的，并表明尽管过去令人失望，但连锁研究可以用于复制其他研究的区域，并可能发现中等至大效应量的新遗传风险因素。考虑到以前的连锁研究在选择和确定方面的差异，这些结果也表明，一些数量性状基因座可能会影响血压和临床高血压的正常范围，而其他基因座则是每个性状所特有的。未来的研究应该集中在这些复制区域的精细定位上，其中包括潜在的候选基因。
Hypertension was one of the first complex traits to be studied and is thought to be influenced by polygenic and multiple environmental risk factors. Several genomic studies have found suggestive logarithm of odds (LOD) scores for either blood pressure or essential hypertension, but few loci have been replicated. In this study, we performed a genome-wide linkage analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP) on 1109 white female dizygotic twin pairs from the TwinsUK registry in London. Multipoint linkage analysis replicated the locations of 3 previously reported linkage peaks: on chromosome 16 at 65 cM (LOD 0.8 for SBP and 1.8 for DBP); on chromosome 17 at 70 cM ( LOD 1.8 SBP); and at 35 cM on chromosome 22 (LOD 0.97 SBP and 0.99 DBP). Results from multipoint analysis showed 1 novel suggestive linkage for SBP (multipoint LOD 2.28; 2-point P=0.0007) at 35 cM on chromosome 11. Results were similar when those on blood pressure medication were excluded. These are encouraging results for hypertensive research and demonstrate that despite past disappointments, linkage studies can be used to replicate regions from other studies and potentially discover new genetic risk factors of moderate to large effect size. Considering the differences in selection and ascertainment of the previous linkage studies, these results also suggest that some quantitative trait loci are likely to influence the normal range of blood pressure and clinical hypertension, whereas others will be specific to each trait. Future studies should focus on the fine mapping of these replicated regions, which include potential candidate genes.