Mapping determinants of human gene expression by regional and genome-wide association
Mapping determinants of human gene expression by regional and genome-wide association
复制标题
DOI：
10.1038/nature04244
复制
发表时间：
2005-10-27
期刊：
影响因子：
64.8
通讯作者：
Burdick, JT
中科院分区：
文献类型：
--
作者：
Cheung, VG;Spielman, RS;Burdick, JT
为了研究基因表达自然变异的遗传基础，我们之前进行了全基因组连锁分析，并绘制了类似1,000种表达表型的决定因素(1)。在本研究中，我们使用来自国际HapMap项目的密集单核苷酸多态性（SNP）标记进行了关联分析(2)。对于374种表型，关联研究仅对来自具有强关联证据的区域的标记进行了关联研究；这些区域都定位在表达基因附近。对于27个表型的子集，使用bb70000个标记进行全基因组关联分析。与连锁峰下标记的关联分析证实了连锁结果，并缩小了许多具有强连锁证据的表型的候选调控区域。全基因组关联分析产生了高度显著的结果，指出了与基因组扫描相同的位置，约有50%的表型。对于一个候选决定因素，我们进行了功能分析，并证实了顺式作用调控活性的变化。我们的研究结果表明，密集SNP图谱的关联研究将确定一些复杂性状或疾病的易感位点或其他决定因素。
To study the genetic basis of natural variation in gene expression, we previously carried out genome-wide linkage analysis and mapped the determinants of similar to 1,000 expression phenotypes(1). In the present study, we carried out association analysis with dense sets of single-nucleotide polymorphism ( SNP) markers from the International HapMap Project(2). For 374 phenotypes, the association study was performed with markers only from regions with strong linkage evidence; these regions all mapped close to the expressed gene. For a subset of 27 phenotypes, analysis of genome-wide association was performed with > 770,000 markers. The association analysis with markers under the linkage peaks confirmed the linkage results and narrowed the candidate regulatory regions for many phenotypes with strong linkage evidence. The genome-wide association analysis yielded highly significant results that point to the same locations as the genome scans for about 50% of the phenotypes. For one candidate determinant, we carried out functional analyses and confirmed the variation in cis-acting regulatory activity. Our findings suggest that association studies with dense SNP maps will identify susceptibility loci or other determinants for some complex traits or diseases.