Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height
Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height
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DOI：
10.1007/s00439-011-1096-4
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发表时间：
2012-03-01
期刊：
影响因子：
5.3
通讯作者：
Lee, Jong-Keuk
中科院分区：
文献类型：
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作者：
Kim, Jae-Jung;Park, Young-Mi;Lee, Jong-Keuk
身高是一个高度遗传的性状，涉及多个遗传位点。为了确定影响身材的因果变异，我们对四名特发性身材矮小儿童的全外显子组进行了测序。95个非同义单核苷酸多态性（nsSNPs）被选为潜在的候选变异。我们对740个队列个体进行了关联分析，在10个基因座（DIS3L2、ZBTB38、FAM154A、PTCH 1、TSSC 4、KIF18A、GPR133、ACAN、FAM59A和NINL）中发现了11个与成人身高相关的nsSNPs（P < 0.05），其中包括5个新基因座。其中，两个nsSNP（TSSC 4和KIF18A基因座）在复制研究中在P < 0.05时显著（n = 1，000），五个nsSNP（ZBTB 38、FAM 154 A、TSSC 4、KIF18A和FAM 59 A基因座）在组合分析中在P < 0.01时显著（n = 1，740）。总之，五个nsSNP占高度变化的约2.5%。这项研究证明了下一代测序在识别与复杂性状相关的遗传变异和基因座方面的实用性。
Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height (P < 0.05), including five novel loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis (n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits.