Center for Genomic Medicine, Institute of Physical and Chemical Research, RIKEN, Kanagawa, Japan.
Hum Mol Genet. 2010 Jun 1;19(11):2303-12. doi: 10.1093/hmg/ddq091. Epub 2010 Feb 26.
Previous genome-wide association studies (GWASs) have identified several loci associated with human height; however, such evidence was mostly reported in Caucasian populations. Since the different distributions of height between populations suggest their different genetic backgrounds, analysis in different populations would be useful. Here, we present the results of a GWAS for adult height in 19 633 Japanese subjects. We found eight significantly associated loci that satisfied the genome-wide significance level (P < 5.0 x 10(-8)). Of these, the association to the LHX3-QSOX2 locus was entirely novel (rs12338076, P = 2.2 x 10(-8)). We also identified the association to the IGF1 locus (rs17032362, P = 8.1 x 10(-9)). Conditional association analysis in the IGF1 locus with rs17032362 suggested the existence of an additional independent association with height to this locus (rs1457595, P = 1.2 x 10(-5)). We observed large differences in the allele frequencies of rs17032362 and rs1457595 between Japanese (34 and 9%, respectively) and Caucasian (1.7 and 0%, respectively) populations, thereby suggesting weak statistical powers for the IGF1 locus in the previous Caucasian GWASs for height. We extensively compared our results with those of previous reports on the Caucasian and Korean populations. We were able to replicate all four loci previously reported in Koreans (EFEMP1, ZBTB38, HMGA1 and PLAG1, P < 5.0 x 10(-8)) and 15 loci identified in Caucasians (P < 0.001). The combination of the height-associated loci identified in our study and the previous GWASs demonstrated an effect size of 1.26 cm (95% confidence interval: 1.18-1.34) per 1.0 increase of the normalized Z score for height-increasing alleles, explaining 4.6% of the total variance of adult height.
先前的全基因组关联研究(GWAS)已经确定了几个与人类身高相关的基因座;然而,这种证据主要是在白种人群中报道的。由于不同人群的身高分布不同,提示其遗传背景不同,在不同人群中的分析将是有用的。在这里,我们报告了在 19633 名日本受试者中进行的成人身高 GWAS 的结果。我们发现了八个与身高显著相关的基因座,达到了全基因组显著水平(P < 5.0 x 10(-8))。其中,与 LHX3-QSOX2 基因座的关联是全新的(rs12338076,P = 2.2 x 10(-8))。我们还发现了 IGF1 基因座的关联(rs17032362,P = 8.1 x 10(-9))。在 IGF1 基因座上与 rs17032362 进行条件关联分析表明,该基因座与身高的另一个独立关联存在(rs1457595,P = 1.2 x 10(-5))。我们观察到 rs17032362 和 rs1457595 在日本人群(分别为 34%和 9%)和高加索人群(分别为 1.7%和 0%)中的等位基因频率存在很大差异,这表明 IGF1 基因座在以前的高加索人群身高 GWAS 中的统计效能较弱。我们广泛比较了我们的结果与以前在白种人和韩国人群中的报告。我们能够复制在韩国人(EFEMP1、ZBTB38、HMGA1 和 PLAG1,P < 5.0 x 10(-8))中以前报道的四个基因座和在白种人(P < 0.001)中确定的 15 个基因座。我们的研究和以前的 GWASs 确定的与身高相关的基因座的组合表明,身高增高等位基因每增加 1.0 个单位,身高的效应大小为 1.26 厘米(95%置信区间:1.18-1.34),解释成人身高总方差的 4.6%。
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