A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci
A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci
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DOI：
10.1093/hmg/ddq091
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发表时间：
2010-06-01
影响因子：
3.5
通讯作者：
Kamatani, Naoyuki
中科院分区：
文献类型：
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作者：
Okada, Yukinori;Kamatani, Yoichiro;Kamatani, Naoyuki
以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，这些证据大多在高加索人群中报道。由于不同群体间的高度分布差异表明其遗传背景不同，因此在不同群体中进行分析将是有益的。在这里，我们介绍了19633名日本受试者的成人身高GWAS结果。我们发现了8个显著相关的位点，满足全基因组显著性水平（P < 5.0 × 10（-8））。其中，与LHX 3-QSOX 2基因座的关联是全新的（rs 12338076，P = 2.2 x 10（-8））。我们还确定了与IGF 1基因座的关联（rs 17032362，P = 8.1 x 10（-9））。IGF 1基因座与rs 17032362的条件关联分析表明，该基因座与身高存在额外的独立关联（rs 1457595，P = 1.2 x 10（-5））。我们观察到日本人（分别为34%和9%）和高加索人（分别为1.7%和0%）人群之间rs 17032362和rs 1457595等位基因频率的巨大差异，从而表明IGF 1基因座在既往高加索人身高GWAS中的统计学功效较弱。我们广泛地比较了我们的结果与以前的报告对高加索和韩国人口。我们能够复制先前在韩国人中报道的所有四个基因座（EFEMP 1、ZBTB 38、HMGA 1和PLAG 1，P < 5.0 x 10（-8））和在高加索人中鉴定的15个基因座（P < 0.001）。在我们的研究和以前的GWAS中确定的身高相关基因座的组合显示，身高增加等位基因的标准化Z得分每增加1.0，效应大小为1.26 cm（95%置信区间：1.18-1.34），解释成人身高总方差的4.6%。
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.