A Two-sample Mendelian Randomization Study of Oily Nut Intake and Primary Lung Cancer
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摘要:
目的 以两样本孟德尔随机化方法探讨油性坚果摄取量与原发性肺癌的因果关系。 方法 从全基因组关联研究openGWAS公开数据库中筛选出与油性坚果摄入量相关的（P < 5×10-7）单核苷酸多态性位点作为工具变量，以逆方差加权法为该研究评估因果效应的主要分析方法，并采用MR-Egger回归和加权中位数法用于补充说明，以OR值及95%CI评价油性坚果摄入量与原发性肺癌之间是否存在因果关系。采用mr_pleiotropy_test法及MR-PRESSO法检验水平多效性，leave-one-out留一法进行敏感性检验。 结果 从ukb-b-16576数据集共提取100个SNP作为工具变量，MR-Egger回归、加权中位数和逆方差加权法计算得OR值和95%可信区间分别[0.63，95%CI（0.11～3.65），P = 0.611]，[0.34，95%CI（0.19～0.61），P = 0.001]，[0.32，95%CI（0.21～0.48），P = 0.001）]，所有b值结果方向均小于0。mr_pleiotropy_test检验显示MR-Egger截距为-7.66E-03，接近于0，P = 0.441，同样MR-PRESSO包GlobalTest检验P = 0.162，所选的工具变量不存在水平多效性，经过leave-one-out敏感性分析，未发现任何SNP位点对结果产生显著影响，表明结果具有较高的稳定性和可靠性。 结论 两样本孟德尔随机化分析表明油性坚果摄入量与原发性肺癌的发病风险呈负向因果关系，但需要更大样本量和不同种族背景的人的数据来进一步验证。 Abstract:Objective To investigate the potential causal relationship between oily nut consumption and primary lung cancer by two-sample Mendelian randomization method. Methods Single nucleotide polymorp hisms （P < 5×10-7） associated with oily nut intake were screened from the openGWAS public database of genome - wide association study as instrumental variables. The inverse variance weighting method was the main analysis method to evaluate the causal effect of this study, and MR-Egger regression and weighted median method were used to supplement the explanation. OR value and 95%CI were used to evaluate whether there was a causal relationship between oily nut intake and primary lung cancer. The mr_pleiotropy_test and MR-PRESSO were used to test the level pleiotropy, and the leave-one-out method was used to test the sensitivity. Results A total of 100 SNPs were extracted from the ukb-b-16576 dataset as instrumental variables. The MR-Egger regression, weighted median, and inverse variance weighting methods yielded OR values and 95% confidence intervals [0.63, 95%CI （0.11-3.65）, P = 0.611], [0.34, 95%CI （0.19-0.61）, P = 0.001], [0.32, 95%CI （0.21-0.48）, P = 0.001], rerespectively. The mr_pleiotropy_test showed that the MR-Egger intercept was close to 0 （-7.66E-03） with a p-value of 0.441, indicating no significant horizontal pleiotropy. Similarly, the MR-PRESSO package GlobalTest yielded a p-value of 0.162, further confirming the absence of horizontal pleiotropy among the selected instrumental variables.After conducting the leave-one-out sensitivity analysis, no significant influence on the results was observed from any specific SNP locus, indicating that the results are highly stable and reliable. Conclusions The two-sample Mendelian randomization analysis revealed a negative causal relationship between oily nut intake and the risk of primary lung cancer. However, further verification is needed with larger sample sizes and data from individuals of different ethnic backgrounds to strengthen the findings. -
Key words:
- Oily nuts /
- Primary lung cancer /
- Mendel randomization /
- Causal inference
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表 1 工具变量SNP信息表
Table 1. Instrumental variable SNP information table
SNP chr EA OA EAF B S R2 F P rs3101339 1 C A 0.6 1.43E−02 1.71E−03 3.36E−03 69.91 6.20E−17 rs10740991 10 C G 0.72 1.67E−02 1.86E−03 3.35E−03 81.23 2.00E−19 rs746868 6 G C 0.61 −1.29E−02 1.71E−03 3.03E−03 56.65 5.20E−14 rs4269101 3 G T 0.72 −1.38E−02 1.86E−03 2.75E−03 55.17 1.10E−13 rs9385269 6 T C 0.52 1.21E−02 1.68E−03 2.65E−03 51.48 7.20E−13 rs4800488 18 A C 0.49 1.20E−02 1.67E−03 2.49E−03 51.36 7.70E−13 rs4149513 2 A G 0.49 1.17E−02 1.67E−03 2.46E−03 49.25 2.20E−12 rs1582322 16 G A 0.6 9.94E−03 1.72E−03 2.32E−03 33.58 6.80E−09 。。。。。。。。。。。。。。。。。。。。。。。。。 。。。。。。。。。。。。。。。。。。。。。。。。。 rs7829800 8 G A 0.67 −1.04E−02 1.79E−03 2.30E−03 34.16 5.10E−09 rs261809 1 G A 0.54 −9.63E−03 1.68E−03 2.17E−03 32.88 9.80E−09 rs6533183 4 T C 0.66 −9.54E−03 1.76E−03 2.16E−03 29.42 5.80E−08 rs4140799 14 A G 0.53 9.46E−03 1.68E−03 2.11E−03 31.74 1.80E−08 rs10087278 8 A G 0.59 8.99E−03 1.70E−03 2.11E−03 27.92 1.30E−07 rs10129747 14 G A 0.53 9.36E−03 1.68E−03 2.07E−03 30.98 2.60E−08 rs3757323 6 C T 0.63 8.90E−03 1.74E−03 2.06E−03 26.28 2.90E−07 rs11073575 15 C T 0.58 −8.90E−03 1.70E−03 2.05E−03 27.28 1.80E−07 
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表 2 5种MR分析方法OR估计值及95%CI
Table 2. OR estimates and 95% CI of five MR analysis methods
method b se P OR 95%CI Q值 Q_pval MR Egger −0 .47 0.89 0.611 0.63（0.11，3.65） 99.32 0.15 Weighted median −1.07 0.29 0.001 0.34（0.19，0.61） 100.01 0.16 Inverse variance weighted −1.14 0.21 0.001 0.32（0.21，0.48） Simple mode −0.99 0.76 0.192 0.37（0.08，1.64） Weighted mode −0.99 0.73 0.173 0.37（0.08，1.51）
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