2型糖尿病与结直肠癌发生风险的两样本孟德尔随机化研究

张俏; 周学志; 陈炳合; 侯栋; 吴新军; 朱绍辉

doi:10.16766/j.cnki.issn.1674-4152.003661

2型糖尿病与结直肠癌发生风险的两样本孟德尔随机化研究

doi: 10.16766/j.cnki.issn.1674-4152.003661

1.
新乡医学院第一附属医院胃肠外科减重代谢与疝外科，河南新乡 453000
2.
新乡医学院医学工程学院，河南新乡 453000

基金项目:

河南省医学科技攻关计划项目 LHGJ20210536

河南省高等学校重点科研项目计划 22B320007

详细信息

通讯作者:
朱绍辉，E-mail：shaohui912@126.com

中图分类号: R587.1 R592
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出版历程
- 收稿日期: 2024-03-26

A two-sample Mendelian randomization study of type 2 diabetes mellitus and colorectal cancer risk

1.
Department of Gastrointestinal Weight Loss Metabolism and Hernia Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, China

摘要

摘要: 目的本研究旨在通过两样本孟德尔随机化(MR)方法探讨2型糖尿病与结直肠癌之间的潜在因果关系。方法取自全基因组关联研究(GWAS)汇总数据集，其中暴露(2型糖尿病)数据490 089例，结局(结直肠癌)数据383 348例。通过剔除连锁不平衡和混杂因素，以及设定关联强度阈值，筛选出47个单核苷酸多态性(SNPs)作为研究的工具变量(IVs)。采用逆方差加权(IVW)法辅以加权中位数法、MR-Egger法、简单模式法和加权模式法评估因果关系。利用留一法进行敏感性分析，并通过可视化手段进一步评估MR分析结果的可靠性和稳健性。同时，使用IVW法和MR-Egger法的Cochran Q检验评估异质性，以及MR-Egger截距法进行多效性检验。结果 IVW法表明两者间不存在显著的因果关联(OR=1.000，95% CI：0.999~1.001，P=0.790)，加权中位数法(P=0.386)、MR-Egger法(P=0.137)、简单模式法(P=0.275)和加权模式法(P=0.479)的分析结果进一步验证了这一发现。留一法分析未发现显著影响整体结果的单个SNP，异质性检验(P＞0.05)和多效性检验(P＞0.05)的结果均佐证了MR结论的可靠性和稳健性。结论 2型糖尿病与结直肠癌之间在遗传学层面不存在明显的因果关联。
- 2型糖尿病 /
- 结直肠癌 /
- 因果关联 /
- 孟德尔随机化
Abstract: Objective This study aims to explore the potential causal relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) using a two-sample Mendelian randomization (MR) method. Methods Summary data were obtained from genome-wide association studies (GWAS) datasets, including 490 089 cases for the exposure (T2DM) and 383 348 cases for the outcome (CRC). To minimize linkage disequilibrium and confounding factors, and to ensure strong association, 47 single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for the study. The inverse variance weighted (IVW) method was used as the primary analysis, with supplementary analysis by the weighted median method, MR-Egger method, simple mode method, and weighted mode method to assess the causal relationship. Sensitivity analysis was conducted using the leave-one-out method, and visual tools were employed to further evaluate the reliability and robustness of the MR results. Heterogeneity was assessed using Cochran ' s Q test for both the IVW method and MR-Egger method, while pleiotropy was evaluated using the MR-Egger intercept method. Results The IVW method indicated no significant causal relationship between T2DM and CRC (OR=1.000, 95% CI: 0.999-1.001, P=0.790). These results were consistent across the weighted median method (P=0.386), MR-Egger method (P=0.137), simple mode method (P=0.275), and weighted mode method (P=0.479). The leave-one-out analysis did not identify any individual SNPs that significantly influenced the overall results. Both heterogeneity tests (P>0.05) and pleiotropy tests (P>0.05) supported the reliability and robustness of the MR conclusions. Conclusion There is no evident genetic causal relationship between T2DM and colorectal cancer.
- Type 2 diabetes mellitus /
- Colorectal cancer /
- Causal relationship /
- Mendelian randomization
利益冲突 无

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图 1 留一法进行的敏感性分析

注：黑点及黑线表示去掉相应的单个SNP重新计算的效应值和95% CI，红点及红线表示总的效应值和95% CI。

Figure 1. Sensitivity analysis by leave-one method

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图 2 MR分析的散点图及拟合曲线图

注：黑点及横纵坐标代表单个SNP对2型糖尿病和结直肠癌的效应，彩色线为对应3种方法计算出的效应值的拟合曲线。

Figure 2. Scatter plot and fitting curve of MR Analysis

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图 3 MR分析的森林图

注：黑点及黑线表示单个SNP的效应值及95% CI，红点及红线表示对应方法计算出总的效应值及95% CI。

Figure 3. Forest map of MR analysis

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图 4 MR分析的漏斗图

注：黑点代表SNP，彩色线为对应方法计算的总效应值。

Figure 4. Funnel diagram of MR Analysis

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表 1 与2型糖尿病/结直肠癌相关的部分SNPs

Table 1. SNPs associated with type 2 diabetes / colorectal cancer

SNP	chr	EA(效应位点)	OA(其他位点)	β	EAF	SE	F值	P值
rs10173251	2	G	C	-0.106	0.112	0.014	56.730	5.86×10^-14
rs10830963	11	G	C	0.050	0.330	0.007	60.122	1.20×10^-14
rs10965250	9	A	G	-0.164	0.236	0.007	507.175	7.70×10^-114
rs11257655	10	T	C	0.108	0.282	0.007	246.809	2.36×10^-55
rs1128249	2	T	G	-0.079	0.300	0.008	101.544	9.30×10^-24
rs115018313	6	C	T	0.284	0.031	0.024	142.391	7.30×10^-33
rs11514706	7	C	A	0.060	0.501	0.006	91.006	8.55×10^-22
rs11651052	17	G	A	-0.091	0.590	0.007	196.000	5.35×10^-44
rs12108088	3	A	G	-0.037	0.439	0.007	31.533	2.21×10^-8
rs1215468	13	G	A	-0.075	0.288	0.007	117.833	3.91×10^-27

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