A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits
A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits
复制标题
DOI：
10.1038/ng.357
复制
发表时间：
2009-05-01
期刊：
影响因子：
30.8
通讯作者：
Kim, Hyung-Lae
中科院分区：
文献类型：
--
作者：
Cho, Yoon Shin;Go, Min Jin;Kim, Hyung-Lae
为了确定影响生物医学重要性数量性状的遗传因素，我们在韩国招募的8,842个基于人群的队列样本中进行了全基因组关联研究。对于身高和身体质量指数，大多数检测到的变异与欧洲样本中报告的重叠。对于研究的其他性状，7861个独立的韩国样本中有希望的GWAS信号的复制确定了6个以前未知的位点。对于脉冲速率，具有全基因组意义的信号定位于染色体1q32 （rs12731740, P = 2.9 x 10(-9)）和6q22 (rs12110693, P = 1.6 x 10(-9))，后者与GJA1编码序列400kb相似。对于收缩压，最引人注目的关联涉及染色体12q21和ATP2B1基因附近的变异（rs17249754, P = 1.3 x 10(-7)）。对于腰臀比，12q24染色体变异（rs2074356, P = 7.8 × 10(-12)）显示出令人信服的相关性，尽管没有区域性转录本具有很强的生物学候选性。最后，我们确定了影响多个部位骨矿物质密度的两个位点。在染色体7q31上，rs7776725 （FAM3C基因内）与桡骨（P = 1.0 x 10(-11)）、胫骨（P = 1.6 x 10(-6)）和足跟（P = 1.9 x 10(-10)）的骨密度相关。在染色体7p14上，rs1721400（定位于卷曲蛋白基因SFRP4附近）在相同的三个位点显示出一致的关联(P = 2.2 × 10（-3), P = 1.4 × 10（-7）和P = 6.0 × 10(-4)）。这种大规模的GWA分析特征良好的韩国人口为基础的样本突出了以前未知的生物学途径。
To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter similar to 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4 x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.