Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach.

Increased Menopausal Age Reduces the Risk of Parkinson's Disease: A Mendelian Randomization Approach.
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DOI:
10.1002/mds.28760
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发表时间:
2021-10
期刊:
Movement disorders : official journal of the Movement Disorder Society
影响因子:
--
通讯作者:
Ritz BR
Ritz BR
中科院分区:
其他
文献类型:
--
作者:
Kusters CDJ;Paul KC;Duarte Folle A;Keener AM;Bronstein JM;Bertram L;Hansen J;Horvath S;Sinsheimer JS;Lill CM;Ritz BR

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PD 及其与初潮或更年期年龄相关性的研究报告了不一致的结果。孟德尔随机化 (MR) 可以解决由于难以准确报告这些生活事件发生的年龄而导致的测量误差。我们采用 MR 来评估绝经年龄和初潮年龄与 PD 风险之间的关联。我们使用来自英国生物库的外部 GWAS 摘要数据以及两项基于人群的研究(丹麦 PASIDA 和美国 PEG)中基因变异和 PD 之间的效应估计进行了逆变异加权 (IVW) MR 分析,这两项研究纳入了 1,737 名欧洲血统女性受试者和 2,430 名欧洲血统男性受试者。然后,我们使用 PD 联盟(19,773 名女性)的汇总统计数据复制了我们对绝经年龄的研究结果,然后结合所有汇总统计数据进行荟萃分析。在我们的研究中,女性绝经年龄每增加一年,PD 风险就会降低(OR:0.84,95%CI:0.73-0.98,P:0.03),而男性则没有相关性(OR:0.98,95%CI:0.85-1.11,P:0.71)。使用 PD 联盟的汇总统计数据进行重复估计 OR 为 0.94(95%CI:0.90 – 0.99,P:0.01),我们计算出荟萃分析 OR 为 0.93(95%CI:0.89 – 0.98,P:0.003)。没有迹象表明初潮年龄与 PD 之间存在关联(OR:0.75,95%CI:0.44-1.29,P:0.29)。女性绝经年龄较晚与帕金森病风险降低相关,这支持了性激素或与绝经晚期相关的其他因素可能对帕金森病具有神经保护作用的假设。
Studies of PD and the association with age at menarche or menopause have reported inconsistent findings. Mendelian Randomization (MR) may address measurement errors due to difficulties accurately reporting the age these life events occur. We employed MR to assess the association between age at menopause and age at menarche with PD risk. We performed inverse variant-weighted (IVW) MR analysis using external GWAS summary data from the UK biobank, and the effect estimates between genetic variants and PD among two population-based studies (PASIDA, Denmark, and PEG, USA) that enrolled 1,737 female and 2,430 male subjects of European ancestry. We then replicated our findings for age at menopause using summary statistics from the PD consortium (19,773 women), followed by a meta-analysis combining all summary statistics. For each year increase in age at menopause, the risk for PD decreased (OR: 0.84, 95%CI: 0.73-0.98, P:0.03) among women in our study, while there was no association among men (OR: 0.98, 95%CI: 0.85-1.11, P:0.71). A replication using summary statistics from the PD consortium estimated an OR of 0.94 (95%CI: 0.90 – 0.99, P: 0.01), and we calculated a meta-analytic OR of 0.93 (95%CI: 0.89 – 0.98, P: 0.003). There was no indication for an association between age at menarche and PD (OR: 0.75, 95%CI: 0.44-1.29, P:0.29). A later age at menopause was associated with a decreased risk of PD in women, supporting the hypothesis that sex hormones or other factors related to late menopause may be neuroprotective in PD.
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