Mendelian randomization of simvastatin in preventing cholelithiasis

doi:10.3877/cma.j.issn.2095-3232.2025022

Abstract

Abstract:

Objective

To analyze related data by genome-wide association studies (GWAS) and evaluate preventive effect of simvastatin on cholelithiasis by Mendelian randomization (MR).

Methods

MR was adopted to evaluate the preventive effect of simvastatin on cholelithiasis with genetic variants as instrumental variables.Based on the published gene data in ieuopen GWAS database, the single nucleotide polymorphism (SNP) with significant association with simvastatin was selected as an instrumental variable using R language platform.The causal association between simvastatin and cholelithiasis was evaluated by inverse-variance weighted (IVW), weighted median (WM) and MR-Egger methods, respectively.The forest and scatter plots of simvastatin and the risk of cholelithiasis associated with SNP were delineated.

Results

A total of 36 SNPs associated with simvastatin were screened.IVW (OR=0.956, 95%CI: 0.935-0.978, P=8.57×10^-5),WM (OR=0.957, 95%CI: 0.926-0.983, P=1.82×10^-3) and MR-Egger regression analyses (OR=0.963,95%CI: 0.922-1.007, P=1.07×10^-1) showed negative causal association between simvastatin and cholelithiasis.MR-Egger regression analysis indicated no pleiotropic effect (intercept=-6.36×10^-5, P=0.69).According to the slope of the straight line in the scatter plot, the causal correlation estimates were similar among IVW, WM and MR-Egger regression methods.With every one standard deviation (SD) increase of simvastatin, the risk of cholelithiasis decreased by approximately 4.4%.

Conclusions

MR analysis of two samples demonstrates that there is a negative causal association between simvastatin and the risk of cholelithiasis.The risk of cholelithiasis will decreased by approximately 4.4% with every one SD increase of simvastatin.

Key words: Simvastatin, Cholelithiasis, Mendelian randomization (MR), Cholesterol saturation index (CSI)

Bin Niu, Linlu She, Kangqiang Weng, Hu Li, Xiang Wu, Yingbo Dai. Mendelian randomization of simvastatin in preventing cholelithiasis[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(01): 60-67.

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染色体编号	坐标位置	单核苷酸多态性位点	辛伐他汀效应等位基因	辛伐他汀其他等位基因	胆石症效应等位基因	胆石症其他等位基因
19	45358353	rs10410835	C	T	C	T
19	45412955	rs1081105	C	A	C	A
4	81181072	rs10857147	T	A	T	A
19	11193091	rs112552009	G	T	G	T
8	19822810	rs11570891	T	C	T	C
1	55505647	rs11591147	T	G	T	G
6	160922870	rs117733303	G	A	G	A
1	109817590	rs12740374	T	G	T	G
5	74656539	rs12916	C	T	C	T
5	156373637	rs13167071	C	G	C	G
2	21263900	rs1367117	A	G	A	G
16	53800954	rs1421085	C	T	C	T
9	22076071	rs1831733	C	T	C	T
20	39142516	rs2207132	A	G	A	G
20	17844492	rs2618567	T	G	T	G
2	227145757	rs2673134	G	A	G	A
8	116650219	rs2737231	G	A	G	A
19	11227480	rs2738447	C	A	C	A
8	126507308	rs2980888	C	T	C	T
6	32582577	rs3104415	C	A	C	A
6	160710851	rs3127580	T	C	T	C
16	72101525	rs34042070	G	C	G	C
10	114754784	rs35198068	C	T	C	T
8	126523523	rs4360309	T	C	T	C
8	18269581	rs57180587	T	A	T	A
19	19379549	rs58542926	T	C	T	C
3	135926622	rs645040	T	G	T	G
1	55521109	rs693668	A	G	A	G
19	45412079	rs7412	T	C	T	C
6	160997118	rs74617384	T	A	T	A
1	6652745	rs7513688	A	G	A	G
1	62999675	rs7534572	G	C	G	C
1	27284913	rs79598313	T	C	T	C
20	62711459	rs8126001	T	C	T	C
6	20686996	rs9368222	A	C	A	C
11	116648917	rs964184	C	G	C	G

染色体编号	坐标位置	单核苷酸多态性位点	辛伐他汀效应等位基因	辛伐他汀其他等位基因	胆石症效应等位基因	胆石症其他等位基因
19	45358353	rs10410835	C	T	C	T
19	45412955	rs1081105	C	A	C	A
4	81181072	rs10857147	T	A	T	A
19	11193091	rs112552009	G	T	G	T
8	19822810	rs11570891	T	C	T	C
1	55505647	rs11591147	T	G	T	G
6	160922870	rs117733303	G	A	G	A
1	109817590	rs12740374	T	G	T	G
5	74656539	rs12916	C	T	C	T
5	156373637	rs13167071	C	G	C	G
2	21263900	rs1367117	A	G	A	G
16	53800954	rs1421085	C	T	C	T
9	22076071	rs1831733	C	T	C	T
20	39142516	rs2207132	A	G	A	G
20	17844492	rs2618567	T	G	T	G
2	227145757	rs2673134	G	A	G	A
8	116650219	rs2737231	G	A	G	A
19	11227480	rs2738447	C	A	C	A
8	126507308	rs2980888	C	T	C	T
6	32582577	rs3104415	C	A	C	A
6	160710851	rs3127580	T	C	T	C
16	72101525	rs34042070	G	C	G	C
10	114754784	rs35198068	C	T	C	T
8	126523523	rs4360309	T	C	T	C
8	18269581	rs57180587	T	A	T	A
19	19379549	rs58542926	T	C	T	C
3	135926622	rs645040	T	G	T	G
1	55521109	rs693668	A	G	A	G
19	45412079	rs7412	T	C	T	C
6	160997118	rs74617384	T	A	T	A
1	6652745	rs7513688	A	G	A	G
1	62999675	rs7534572	G	C	G	C
1	27284913	rs79598313	T	C	T	C
20	62711459	rs8126001	T	C	T	C
6	20686996	rs9368222	A	C	A	C
11	116648917	rs964184	C	G	C	G

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