循环脂质和降脂药物对癫痫风险的因果影响：两样本孟德尔随机化研究。

Causal effects of circulating lipids and lipid-lowering drugs on the risk of epilepsy: a two-sample Mendelian randomization study.

机构信息

Department of Neurology, The Third Hospital of Jilin University, Jilin University, Changchun, China.

Department of Neurology, The First Hospital of Jilin University, Changchun, China.

出版信息

QJM. 2023 Jun 8;116(6):421-428. doi: 10.1093/qjmed/hcad048.

DOI:10.1093/qjmed/hcad048

PMID:36964718

Abstract

BACKGROUND

Previous studies have reported inconsistent results on the association between circulating lipids and lipid-lowering drugs with the risk of epilepsy.

AIM

To assess whether genetically predicted circulating lipids and lipid-lowering drugs are causally associated with the risk of epilepsy outcome.

METHODS

We performed a two-sample Mendelian randomization (MR) analysis model to genetically predict the causal effects of circulating lipids (apolipoprotein A [APOA], apolipoprotein B [APOB], cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], lipoprotein A and triglycerides) and lipid-lowering drugs (HMG-CoA reductase [HMGCR] and proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) on epilepsy. Nine MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (simple mode, weighted mode, simple median, weighted median, penalized weighted median, MR Egger and MR-Egger [bootstrap]) were conducted as the complement to IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis.

RESULTS

The IVW analysis method demonstrated that there is no causal association between circulating lipids (APOA: odds ratio [OR], 0.958, 95% confidence interval (CI), 0.728-1.261, P = 0.760; APOB: OR, 1.092; 95% CI, 0.979-1.219, P = 0.115; cholesterol: OR, 1.210; 95% CI, 0.981-1.494, P = 0.077; HDL-C: OR, 0.964; 95% CI, 0.767-1.212, P = 0.753; LDL-C: OR, 1.100; 95% CI, 0.970-1.248, P = 0.137; lipoprotein A: OR, 1.082; 95% CI, 0.849-1.379, P = 0.528; triglycerides: OR, 1.126; 95% CI, 0.932-1.360, P = 0.221) and lipid-lowering drugs (HMGCR inhibitors: OR, 0.221; 95% CI, 0.006-8.408, P = 0.878; PCSK9 inhibitors: OR, 1.112; 95% CI, 0.215-5.761, P = 0.902) with risk of epilepsy. The other MR analysis methods and further leave-one-out sensitivity analysis confirmed the robustness of final results.

CONCLUSION

This MR study demonstrated that there were no genetically predicted causal relationships between circulating lipids and lipid-lowering drugs with the risk of epilepsy.

摘要

背景

先前的研究报告称，循环脂质与降脂药物与癫痫风险之间的关联结果不一致。

目的

评估遗传预测的循环脂质和降脂药物是否与癫痫结局的风险存在因果关系。

方法

我们进行了两样本孟德尔随机化（MR）分析模型，以遗传预测循环脂质（载脂蛋白 A [APOA]、载脂蛋白 B [APOB]、胆固醇、高密度脂蛋白胆固醇 [HDL-C]、低密度脂蛋白胆固醇 [LDL-C]、脂蛋白 A 和甘油三酯）和降脂药物（羟甲基戊二酰辅酶 A [HMG-CoA]还原酶和前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9 [PCSK9]抑制剂）与癫痫风险之间的因果关系。进行了 9 种 MR 分析方法来分析最终结果。反方差加权（IVW）方法作为主要结果。其他 MR 分析方法（简单模式、加权模式、简单中位数、加权中位数、惩罚加权中位数、MR Egger 和 MR-Egger [自举]）作为 IVW 的补充。此外，通过逐一剔除分析评估 MR 分析结果的稳健性。

结果

IVW 分析方法表明，循环脂质（APOA：比值比 [OR]，0.958，95%置信区间 [CI]，0.728-1.261，P=0.760；APOB：OR，1.092；95%CI，0.979-1.219，P=0.115；胆固醇：OR，1.210；95%CI，0.981-1.494，P=0.077；HDL-C：OR，0.964；95%CI，0.767-1.212，P=0.753；LDL-C：OR，1.100；95%CI，0.970-1.248，P=0.137；脂蛋白 A：OR，1.082；95%CI，0.849-1.379，P=0.528；甘油三酯：OR，1.126；95%CI，0.932-1.360，P=0.221）和降脂药物（HMG-CoA 还原酶抑制剂：OR，0.221；95%CI，0.006-8.408，P=0.878；PCSK9 抑制剂：OR，1.112；95%CI，0.215-5.761，P=0.902）与癫痫风险之间没有遗传预测的因果关系。其他 MR 分析方法和进一步的逐一剔除敏感性分析证实了最终结果的稳健性。