Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population.
Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population.
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使用中国人群全基因组关联研究的数据估计九种常见癌症的遗传力
DOI：
10.1002/ijc.30447
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发表时间：
2017-01-15
影响因子：
6.4
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Dai J;Shen W;Wen W;Chang J;Wang T;Chen H;Jin G;Ma H;Wu C;Li L;Song F;Zeng Y;Jiang Y;Chen J;Wang C;Zhu M;Zhou W;Du J;Xiang Y;Shu XO;Hu Z;Zhou W;Chen K;Xu J;Jia W;Lin D;Zheng W;Shen H
家族聚集性表明癌症风险具有遗传性。最近的全基因组关联研究（GWAS）已经确定了一些常见的单核苷酸多态性（SNP）。以下遗传力分析表明，SNP可以解释高加索人中不同癌症表型的中等变异量。然而，中国人群中的信息很少。我们对中国人群（14，629例癌症病例与17，554例对照）9个解剖部位的常见癌症进行了全基因组复杂性状分析（GCTA），并基于常见SNP估计了这些癌症的遗传度。我们发现，常见的SNP解释了所有九个癌症部位的一定量的遗传性：胃癌食管鳞癌占20.26%（19.86%），结直肠癌（16.30%），肺癌（15.17%）和上皮性卵巢癌HBV相关的肝细胞癌、前列腺癌、乳腺癌和鼻咽癌的遗传度均在10%左右。我们发现，当去除GWAS报告的SNP的向上和向下扩展250kb或500kb的区域时，显示出接近或小于25%的变化。肺癌（R2= 0.641，P =0.001）和食管鳞癌（R2= 0.633，P =0.002）的染色体长度与各染色体划分的方差之间存在较强的线性相关性，提示了癌症的复杂异质性。这些结果表明，中国人群中9种常见癌症的遗传结构是多基因的。应进一步努力发现中国人不同癌症类型的隐藏遗传力。
The familial aggregation indicated the inheritance of cancer risk. Recent genome-wide association studies (GWAS) have identified a number of common single nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis (GCTA) for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for Hepatitis B virus (HBV)-related hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250kb or 500kb up and downwards of the GWAS-reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for lung cancer (R2=0.641, P=0.001) and esophageal squamous cell cancer (R2=0.633, P=0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese.
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影响因子：
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作者：
Kimura T
通讯作者：
Kimura T
影响因子：
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作者：
Bei, Jin-Xin;Li, Yi;Zeng, Yi-Xin
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Hemminki, K
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通讯作者：
Visscher PM