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探讨家庭收入状况与神经系统疾病遗传易感性之间的双向因果关系:孟德尔随机化研究的结果。

Exploring the bidirectional causal link between household income status and genetic susceptibility to neurological diseases: findings from a Mendelian randomization study.

机构信息

Department of Neurology, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, China.

出版信息

Front Public Health. 2023 Jul 26;11:1202747. doi: 10.3389/fpubh.2023.1202747. eCollection 2023.

Abstract

OBJECTIVES

Observational studies have revealed that socioeconomic status is associated with neurological disorders and aging. However, the potential causal effect between the two remains unclear. We therefore aimed to investigate the causal relationship between household income status and genetic susceptibility to neurological diseases using a bidirectional Mendelian randomization (MR) study.

METHODS

An MR study was conducted on a large-sample cohort of the European population pulled from a publicly available genome-wide association study dataset, using a random-effects inverse-variance weighting model as the main standard. MR-Egger regression, weighted median, and maximum likelihood estimation were also performed concurrently as supplements. A sensitivity analysis, consisting of a heterogeneity test and horizontal pleiotropy test, was performed using Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of the conclusion.

RESULTS

The results suggested that higher household income tended to lower the risk of genetic susceptibility to Alzheimer's disease (odds ratio [OR]: 0.740, 95% confidence interval [CI] = 0.559-0.980, -value = 0.036) and ischemic stroke (OR: 0.801, 95% CI = 0.662-0.968, -value = 0.022). By contrast, higher household income tended to increase the risk of genetic susceptibility to Parkinson's disease (OR: 2.605, 95% CI = 1.413-4.802, -value = 0.002). No associations were evident for intracranial hemorrhage (OR: 1.002, 95% CI = 0.607-1.653, -value = 0.993), cerebral aneurysm (OR: 0.597, 95% CI = 0.243-1.465, -value = 0.260), subarachnoid hemorrhage (OR: 1.474, 95% CI = 0.699-3.110, -value = 0.308), or epilepsy (OR: 1.029, 95% CI = 0.662-1.600, -value = 0.899). The reverse MR study suggested no reverse causal relationship between neurological disorders and household income status. A sensitivity analysis verified the reliability of the results.

CONCLUSION

Our results revealed that the populations with a superior household income exhibit an increased predisposition of genetic susceptibility to Parkinson's Disease, while demonstrating a potential decreased genetic susceptibility to ischemic stroke and Alzheimer's disease.

摘要

目的

观察性研究表明,社会经济地位与神经退行性疾病和衰老有关。然而,两者之间的潜在因果关系尚不清楚。因此,我们旨在使用双向孟德尔随机化(MR)研究调查家庭收入状况与神经疾病遗传易感性之间的因果关系。

方法

使用来自公开可用的全基因组关联研究数据集的欧洲人群的大型样本队列进行 MR 研究,使用随机效应逆方差加权模型作为主要标准。同时还进行了 MR-Egger 回归、加权中位数和最大似然估计作为补充。使用 Cochran's Q、MR-Egger 截距和 MR-PRESSO 检验进行异质性检验和水平多效性检验的敏感性分析,以确保结论的可靠性。

结果

结果表明,较高的家庭收入往往会降低患阿尔茨海默病(优势比[OR]:0.740,95%置信区间[CI]:0.559-0.980,-值=0.036)和缺血性中风(OR:0.801,95% CI:0.662-0.968,-值=0.022)的遗传易感性风险。相比之下,较高的家庭收入往往会增加患帕金森病(OR:2.605,95% CI:1.413-4.802,-值=0.002)的遗传易感性风险。颅内出血(OR:1.002,95% CI:0.607-1.653,-值=0.993)、脑动脉瘤(OR:0.597,95% CI:0.243-1.465,-值=0.260)、蛛网膜下腔出血(OR:1.474,95% CI:0.699-3.110,-值=0.308)和癫痫(OR:1.029,95% CI:0.662-1.600,-值=0.899)的遗传易感性无相关性。反向 MR 研究表明,神经障碍与家庭收入状况之间不存在反向因果关系。敏感性分析验证了结果的可靠性。

结论

我们的结果表明,社会经济地位较高的人群对帕金森病的遗传易感性增加,而对缺血性中风和阿尔茨海默病的遗传易感性可能降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b7a/10411908/f6f5f645e5aa/fpubh-11-1202747-g001.jpg

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