Background

Findings from randomized controlled trials have yielded conflicting results on the association between blood pressure (BP) and dementia traits. We tested the hypothesis that a causal relationship exists between systolic BP (SBP) and/or diastolic BP (DBP) and risk of Alzheimer’s disease (AD).

Methods

We performed a generalized summary Mendelian randomization (GSMR) analysis using summary statistics of a genome-wide association study meta-analysis of 299,024 individuals of SBP or DBP as exposure variables against three different outcomes: 1) AD diagnosis (International Genomics of Alzheimer's Project), 2) maternal family history of AD (UK Biobank), and 3) paternal family history of AD (UK Biobank). Finally, a combined meta-analysis of 368,440 individuals that included these three summary statistics was used as final outcome.

Results

GSMR applied to the International Genomics of Alzheimer's Project dataset revealed a significant effect of high SBP lowering the risk of AD (β_GSMR = −0.19, p = .04). GSMR applied to the maternal family history of AD UK Biobank dataset (SBP [β_GSMR = −0.12, p = .02], DBP [β_GSMR = −0.10, p = .05]) and to the paternal family history of AD UK Biobank dataset (SBP [β_GSMR = −0.16, p = .02], DBP [β_GSMR = −0.24, p = 7.4 × 10⁻⁴]) showed the same effect. A subsequent combined meta-analysis confirmed the overall significant effect for the other SBP analyses (β_GSMR = −0.14, p = .03). The DBP analysis in the combined meta-analysis also confirmed a DBP effect on AD (β_GSMR = −0.14, p = .03).

Conclusions

A causal effect exists between high BP and a reduced late-life risk of AD. The results were obtained through careful consideration of confounding factors and the application of complementary MR methods on independent cohorts.

中文翻译：

---

高血压和痴呆症的风险：英国生物库中的两样本孟德尔随机研究

背景

随机对照试验的结果在血压（BP）与痴呆症特征之间的关联上产生了矛盾的结果。我们检验了这一假设，即收缩压（SBP）和/或舒张压（DBP）与阿尔茨海默氏病（AD）风险之间存在因果关系。

方法

我们对299,024名SBP或DBP个体进行了全基因组关联研究的荟萃分析，作为针对三种不同结果的暴露变量，进行了广义孟德尔随机（GSMR）分析：1）AD诊断（阿尔茨海默病项目的国际基因组学） ，2）AD的母系家族史（UK Biobank）和3）AD的母系家族史（UK Biobank）。最后，将包含这三个摘要统计信息的368,440个人的综合荟萃分析用作最终结果。

结果

应用于阿尔茨海默病国际基因组学项目数据集的GSMR显示出高SBP降低AD风险的显着效果（_βGSMR  = -0.19，p  = .04）。GSMR应用于AD UK生物库数据集的母系家族史（SBP [ _βGSMR  = -0.12，p  = .02]，DBP [ _βGSMR  = -0.10，p  = .05]）和AD UK的_母系家族史生物库数据集（SBP [ _βGSMR  = -0.16，p  = .02]，DBP [ _βGSMR  = -0.24，p  = 7.4×10 ^-4 ]）显示了相同的效果。随后的合并荟萃分析证实了其他SBP分析的总体显着效果（β_GSMR  = -0.14，p  = .03）。联合荟萃分析中的DBP分析还证实了DBP对AD的影响（_βGSMR  = -0.14，p  = .03）。

结论

高血压与降低的AD晚期风险之间存在因果关系。通过仔细考虑混杂因素并在独立队列中应用补充MR方法获得了结果。