Estimating the heritability of colorectal cancer
Estimating the heritability of colorectal cancer
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DOI：
10.1093/hmg/ddu087
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发表时间：
2014-07-15
影响因子：
3.5
通讯作者：
Hsu, Li
中科院分区：
文献类型：
--
作者：
Jiao, Shuo;Peters, Ulrike;Hsu, Li
预计很大一部分结直肠癌 (CRC) 可以通过遗传因素来解释，双胞胎和家族研究的遗传率估计范围为 12% 至 35%。全基因组关联研究 (GWAS) 已成功鉴定出许多与 CRC 风险相关的常见单核苷酸多态性 (SNP)。尽管已经证明这些CRC易感性SNP仅解释了一小部分遗传风险，但尚不清楚这些SNP解释了多少遗传性，以及还有多少有待其他尚未鉴定的常见SNP检测。因此，我们利用结直肠癌遗传学和流行病学联盟中的全基因组复杂性状分析（包括 8025 例病例和 10 814 例对照）估计了不同情况下 CRC 的遗传力。我们估计，GWAS 中发现的已知常见 CRC SNP 解释的遗传力为 0.65%（95% CI：0.3-1%；P = 1.11 x 10-16），而所有常见 SNP 解释的遗传力至少为 7.42%（95% CI：4.71-10.12%；P = 8.13 x 10(-8)），这表明许多与 CRC 风险相关的常见变异仍有待检测。将常见变异解释的遗传力与双胞胎和家庭研究的遗传力进行比较，一小部分遗传力可能是由其他遗传变异（例如罕见变异）解释的。此外，我们的分析表明，基因 x 吸烟相互作用解释了很大一部分 CRC 方差 (P = 1.26 x 10(-2))。总之，我们的结果表明已知的 CRC SNP 只能解释一小部分遗传力，更常见的 SNP 尚未确定。
A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 x 10-16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71-10.12%; P = 8.13 x 10(-8)), suggesting that many common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene x smoking interaction explained a significant proportion of the CRC variance (P = 1.26 x 10(-2)). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.