脂蛋白a水平与不同类型痴呆发生风险的相关性研究

A study of the relationship between lipoprotein a levels and the risk of developing different types of dementia

目的:评估脂蛋白a水平与不同类型痴呆(阿尔茨海默病、路易体痴呆、额颞叶痴呆、帕金森病相关痴呆,血管性痴呆)发生风险之间相关性。方法:采用两样本孟德尔随机化研究方法,通过全基因组关联研究(genome-wide association study,GWAS)汇总数据集获得与脂蛋白a水平密切相关的遗传位点作为工具变量(IV),分别与不同类型痴呆进行两样本孟德尔随机化(TSMR)分析,以随机效应逆方差加权法(IVW)的结果为主。以MR-Egger法进行多效性分析、留一法进行敏感性分析来验证数据的可靠性。结果:脂蛋白a水平升高与路易体痴呆风险呈正相关(OR=1.68,P=0.0005),和阿尔茨海默病(Alzheimer's disease,AD)的发生呈负相关(OR=0.95,P=0.0027),与血管性痴呆、额颞叶痴呆、帕金森相关痴呆未发现明显相关性。结论:脂蛋白a水平可能与路易体痴呆发病风险呈正相关,可能与阿尔茨海默病发病风险呈负相关,与其它类型痴呆无明显相关性。

Objective:To assess the potential relationship between lipoprotein(a)levels and the risk of developing different types of dementia(Alzheimer's disease,dementia with Lewy bodies,frontotemporal lobe dementia,Parkinson's disease-associated dementia,and vascular dementia)using a two-sample Mendelian randomization study approach.Methods:Genetic loci closely associated with lipoprotein(a)levels were obtained as instrumental variables(IVs)from the genome-wide association study(GWAS)pooled dataset,and two-sample Mendelian randomization(TSMR)analysis was performed with different types of dementia,with the results of the random-effects inverse variance weighting(IVW)method main.The reliability of the data was verified by multiple validity analysis using the MR-Egger method and sensitivity analysis using the leave-one-out method.Results:Elevated lipoprotein(a)levels were positively correlated with Lewy body dementia(OR=1.67,P=0.0005)and negatively correlated with the development of Alzheimer's disease(OR=0.95,P=0.036),and no significant correlation was found with vascular dementia,frontotemporal lobe dementia,and Parkinson's-related dementia.Conclusion:Lipoprotein(a)levels may be positively associated with the risk of developing dementia with Lewy bodies,may be negatively associated with the risk of developing Alzheimer's disease,and are not significantly associated with other types of dementia.