Differences in asthma genetics between Chinese and other populations
Differences in asthma genetics between Chinese and other populations
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DOI：
10.1016/j.jaci.2013.09.018
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发表时间：
2014-01-01
影响因子：
14.2
通讯作者：
Wong, Gary W. K.
中科院分区：
文献类型：
--
作者：
Leung, Ting F.;Ko, Fanny W. S.;Wong, Gary W. K.
哮喘是由复杂的基因-基因和基因-环境相互作用引起的。大多数哮喘基因在人群中是不可复制的，这可能是因为这些基因的流行病学差异。我们的病例对照关联和下一代测序研究揭示了中国人和其他人群之间哮喘基因单核苷酸多态性（SNP）和单倍型块频率的显著差异。在我们研究的SNPs中，近一半的次要等位基因频率在香港的中国南方受试者与欧洲白色人群、非洲人群或两者之间相差0.2或更大。由于尚未在中国受试者中进行哮喘的全基因组关联研究，因此我们无法判断最近基于联盟的全基因组关联研究的基因组结果是否适用于我们的人群。此外，我们的研究小组对24名健康香港儿童的10个哮喘基因座的100 kb区域进行了Roche 454焦磷酸测序。在17 q21位点，在1000个基因组计划下，由香港受试者和6个种族的224个常见SNPs构建的单倍型结构中存在显著差异。在香港形成了16个主要是小的单倍型块，而在北京汉族和中欧受试者中鉴定出6个单倍型块，在波多黎各和约鲁巴非洲受试者中鉴定出11个和19个单倍型块。总之，中国人哮喘基因的等位基因频率和单倍型结构与其他民族存在差异。这些序列变异必须在选择标记SNP以复制种群之间的遗传关联期间加以考虑。
Asthma is caused by complex gene-gene and gene-environment interactions. Most asthma genes are not replicable across populations, which is possibly because of differences in the epidemiology of these genes. Our case-control association and next-generation sequencing studies revealed substantial discrepancies in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes between Chinese and other populations. The minor allele frequencies for nearly half of our studied SNPs differed by 0.2 or greater between southern Chinese subjects in Hong Kong and European white populations, African populations, or both. Because genome-wide association studies for asthma have not been performed in Chinese subjects, we cannot tell whether the genomic findings of recent consortium-based genome-wide association studies are applicable to our population. In addition, our group performed Roche 454 pyrosequencing on a 100-kb area spanning each of 10 asthma loci in 24 healthy Hong Kong children. For the 17q21 locus, there was substantial variation in the haplotype structures that were constructed from 224 common SNPs among Hong Kong subjects and 6 ethnic groups under the 1000 Genomes Project. Sixteen mostly small haplotype blocks were formed in Hong Kong, whereas 6 haplotype blocks were identified in Han Chinese in Beijing and central European subjects and 11 and 19 blocks were identified in Puerto Rican and Yoruba African subjects. In conclusion, differences in allele frequencies of asthma genes and haplotype structures of asthma loci are found between Chinese subjects and other ethnic groups. These sequence variations must be considered during the selection of tagging SNPs for replicating genetic associations between populations.