Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females.

Runs of homozygosity associate with decreased risks of lung cancer in never-smoking East Asian females.
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纯合性的运行与从不吸烟的东亚女性患肺癌的风险降低相关

DOI:
10.7150/jca.22855
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发表时间:
2018
期刊:
影响因子:
3.9
通讯作者:
Yang TL
Yang TL
中科院分区:
医学3区
文献类型:
--
作者:
Chen YX;Guo Y;Dong SS;Chen XF;Chen JB;Zhang YJ;Yao S;Thynn HN;Zhi L;Yang TL

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尽管全基因组关联研究(GWAS)已经在东亚从不吸烟的女性中发现了一些危险的单核苷酸多态,但原因不明的缺失遗传力仍然需要调查。纯合游程(RoHS)被认为是一种作用于人类复杂特征和疾病的遗传变异。我们在8881名东亚从不吸烟的女性中检测到了RoHS。使用汇总的RoHS来拟合Logistic回归模型,该模型值得注意地显示RoHS与肺癌风险的降低显著相关(P<0.05)。我们发现了位于2p22.1的4个常见RoHS区域,它们与肺癌风险的降低显著相关(P=2.00×10-4-1.35×10-4)。用功能注释的方法研究RoHS的调控功能。在肺来源的细胞系中,常见的RoHS与潜在的调控元件重叠,如活性表观基因组元件和染色质状态。根据差异表达基因的分析,SOS1和ARHGEF33作为已鉴定的RoHS在肺癌样本中的可能的靶基因显著上调。我们的结果表明,RoHS可能作为隐性致病因素和调节元件影响从不吸烟的东亚女性患肺癌的风险。
Although genome-wide association studies (GWASs) have identified some risk single-nucleotide polymorphisms in East Asian never-smoking females, the unexplained missing heritability is still required to be investigated. Runs of homozygosity (ROHs) are thought to be a type of genetic variation acting on human complex traits and diseases. We detected ROHs in 8,881 East Asian never-smoking women. The summed ROHs were used to fit a logistic regression model which noteworthily revealed a significant association between ROHs and the decreased risk of lung cancer (P < 0.05). We identified 4 common ROHs regions located at 2p22.1, which were significantly associated with decreased risk of lung cancer (P = 2.00 × 10-4 - 1.35 × 10-4). Functional annotation was conducted to investigate the regulatory function of ROHs. The common ROHs were overlapped with potential regulatory elements, such as active epigenome elements and chromatin states in lung-derived cell lines. SOS1 and ARHGEF33 were significantly up-regulated as the putative target genes of the identified ROHs in lung cancer samples according to the analysis of differently expressed genes. Our results suggest that ROHs could act as recessive contributing factors and regulatory elements to influence the risk of lung cancer in never-smoking East Asian females.
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