The Shared Genetic Architectures Between Lung Cancer and Multiple Polygenic Phenotypes in Genome-Wide Association Studies.
The Shared Genetic Architectures Between Lung Cancer and Multiple Polygenic Phenotypes in Genome-Wide Association Studies.
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DOI：
10.1158/1055-9965.epi-20-1635
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发表时间：
2021-06
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影响因子：
--
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中科院分区：
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--
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先前的全基因组关联研究已经确定了许多肺癌风险位点，并揭示了组织学亚型之间的显着病因异质性。分析复杂性状变异背后的共同遗传结构可以阐明跨表型的常见遗传病因。探索肺癌与其他多基因性状之间的成对遗传相关性可以揭示相关表型的常见遗传病因。利用跨性状连锁不平衡评分回归，我们利用公开的汇总统计数据估计了肺癌与多个性状之间的成对遗传相关性和遗传力。在排除已知与吸烟行为（肺癌的主要危险因素）相关的基因组区域后，还对已确定的遗传关系进行了检查。我们观察到几个性状显示出中等的基于 SNP 的遗传力以及与肺癌的显着遗传相关性。我们观察到所有组织学亚型的肺癌和肺气肿/慢性支气管炎的遗传结构之间以及吸烟者中发生的肺癌之间存在高度显着的相关性。我们的分析显示肺癌与父亲肺癌病史之间存在高度显着的正相关性。我们还观察到与父母寿命的强烈负相关。在排除与吸烟行为相关的基因组区域后，我们观察到遗传模式的一致方向。这项研究确定了许多与肺癌发生共享基因组结构的表型特征，但已知的与吸烟相关的基因组位点并未完全解释这些特征。这些发现通过识别与肺癌风险增加遗传相关的特征，为肺癌病因学提供了新的见解。
Prior genome-wide association studies have identified numerous lung cancer risk loci and reveal substantial etiologic heterogeneity across histological subtypes. Analyzing the shared genetic architecture underlying variation in complex traits can elucidate common genetic etiologies across phenotypes. Exploring pairwise genetic correlations between lung cancer and other polygenic traits can reveal the common genetic etiology of correlated phenotypes. Using cross-trait linkage disequilibrium score regression, we estimated the pairwise genetic correlation and heritability between lung cancer and multiple traits using publicly available summary statistics. Identified genetic relationships were also examined after excluding genomic regions known to be associated with smoking behaviors, a major risk factor for lung cancer. We observed several traits showing moderate SNP-based heritability and significant genetic correlations with lung cancer. We observed highly significant correlations between the genetic architectures of lung cancer and emphysema/chronic bronchitis across all histological subtypes, as well as among lung cancer occurring among smokers. Our analyses revealed highly significant positive correlations between lung cancer and paternal history of lung cancer. We also observed a strong negative correlation with parental longevity. We observed consistent directions in genetic patterns after excluding genomic regions associated with smoking behaviors. This study identifies numerous phenotypic traits that share genomic architecture with lung carcinogenesis and are not fully accounted for by known smoking-associated genomic loci. These findings provide new insights into the etiology of lung cancer by identifying traits that are genetically correlated with increased risk of lung cancer.
饮食，吸烟和肺癌：一项对西南英格兰1000例和1500例对照的病例对照研究。
影响因子：
8.8
作者：
Darby, S;Whitley, E;Doll, R;Key, T;Silcocks, P
通讯作者：
Silcocks, P