胆固醇水平与神经源性膀胱风险的因果关系

Causality between serum cholesterol concentration and neurogenic bladder risk

摘要

目的 采用孟德尔随机化(Mendelian randomization, MR)方法评估血清胆固醇水平与神经源性膀胱(neurogenic bladder, NB)风险之间的潜在因果关联。 方法 基于公开的全基因组关联研究汇总数据,筛选与血清胆固醇水平显著相关的遗传变异作为工具变量,采用逆方差加权法、MR-Egger回归、加权中值法等多种MR分析方法,在欧洲人群和东亚人群中分别进行评估,以考察结果在不同祖源人群中的一致性。 结果 欧洲人群MR分析显示,遗传预测的血清胆固醇水平与NB风险呈负向关联(IVW: OR=0.776,95%CI: 0.656~0.917,P=0.003)。多种敏感性分析未发现水平多效性或异质性。东亚人群分析结果效应方向与欧洲人群一致,但关联无统计学意义。多变量MR分析在调整体质量指数、体育运动和2型糖尿病后,胆固醇与NB的负向关联仍差异有统计学意义(OR=0.890,95%CI: 0.835~0.947,P=0.041)。 结论 遗传预测的较高胆固醇水平对NB具有保护作用。胆固醇代谢通路可能在NB的病理生理过程中扮演重要角色。

Abstract

Objective To evaluate the potential causal association between serum cholesterol levels and the risk of neurogenic bladder(NB)using a Mendelian randomization(MR)approach. Methods Summary statistics from publicly available genome-wide association studies were used to identify genetic variants significantly associated with serum cholesterol levels as instrumental variables. Multiple MR methods, including inverse variance weighting, MR-Egger regression, and weighted median, were applied. Analyses were conducted separately in European and East Asian populations to assess the consistency of the findings across different ancestral backgrounds. Results MR analysis in the European population demonstrated a negative association between genetically predicted serum cholesterol levels and NB risk(IVW:OR=0.776, 95%CI: 0.656-0.917, P=0.003). Sensitivity analyses revealed no substantial evidence of horizontal pleiotropy or heterogeneity. The effect direction in the East Asian population was consistent with that in the European population, although not statistically significant. Multivariable MR analysis showed that the negative association between cholesterol and NB remained statistically significant after adjusting for body mass index, physical activity, and type 2 diabetes(OR=0.890, 95%CI: 0.835-0.947, P=0.041). Conclusion Genetically predicted higher cholesterol levels have a protective effect against NB. Cholesterol metabolism pathways may play an important role in the pathophysiology of NB.

关键词

神经源性膀胱 / 胆固醇 / 两样本孟德尔随机化 / 多变量孟德尔随机化 / 全基因组关联研究 / 工具变量

Key words

Neurogenic bladder / Cholesterol / Two-sample Mendelian randomization / Multivariable Mendelian randomization / Genome-wide association study / Instrumental variables

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基金资助

山东省泰山青年学者基金(Tsqn202103198)