两样本孟德尔随机化研究肢端肥大症与结肠癌的因果关系
Causal Relationship Between Acromegaly and Colon Cancer: A Two-sample Mendelian Randomization Study
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摘要:目的 使用两样本孟德尔随机化研究肢端肥大症与结肠癌之间的因果关系。方法 筛选出全基因组关联研究(GWAS)与肢端肥大症密切相关的遗传位点作为工具变量, 与来自不同GWAS的结肠癌遗传数据进行两样本孟德尔随机化分析。采用随机效应模型的逆方差加权法(IVW)进行分析, 并以MR-Weighted-Median和MR-Egger法进行补充, 结果以OR值进行呈现。结果 共获得4个与肢端肥大症密切相关的SNPs作为工具变量, 工具变量的多效性检验显示P=0.59。因果效应估计结果采用三种分析方法, IVW分析结果显示: OR=1.00(0.999~1.001), P=0.42, MR-Egger分析结果显示: OR=1.00(0.99~1.001), P=0.42, Weighted-Median分析结果显示: OR=1.00(1.00~1.001), P=0.03。敏感性检验显示工具变量SNP的置信区间均经过0, 说明本孟德尔随机化研究的结果比较稳健。结论 肢端肥大症不是结肠癌的独立危险因素。Abstract:Objective To determine the causal relationship between acromegaly and colon cancer by using two-sample Mendelian randomization.Methods Genetic loci closely related to acromegaly in the whole genome-wide association study (GWAS) were selected as tool variables, and the genetic data of colon cancer from different GWASs were analyzed by two-sample Mendelian randomization (MR).The inverse variance weighting method (IVW) of the random effect model was used for analysis, and MR-weighted median and MR-Egger methods were used to supplement the analysis. Results were presented as OR values.Results Four SNPs closely related to acromegaly were obtained as tool variables, and the multiplicity test of tool variables showed that P=0.59.Three methods were used to estimate causal effects.The IVW analysis were OR=1.00(0.99-1.001) and P=0.42;the MR-Egger analysis results were OR=1.00(0.99-1.001) and P=0.42;and the Weighted median analysis results were OR=1.00(1.00-1.001) and P=0.03.The sensitivity test showed that the confidence interval of the tool variable SNP passed through 0, indicating the robustness of the MR results.Conclusion Acromegaly is not an independent risk factor for colon cancer.
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