High Blood Pressure and Risk of Dementia: A Two-Sample Mendelian Randomization Study in the UK Biobank

孟德尔随机化 生命银行 痴呆 医学 样品(材料) 内科学 血压 随机化 心理学 随机对照试验 生物信息学 遗传学 生物 疾病 基因型 基因 化学 遗传变异 色谱法
作者
William Sproviero,Laura Winchester,Danielle Newby,Marco Fernandes,Liu Shi,Sarah Goodday,Albert Prats‐Uribe,D Prieto Alhambra,Noel J. Buckley,Alejo Nevado‐Holgado
出处
期刊:Biological Psychiatry [Elsevier BV]
卷期号:89 (8): 817-824 被引量:51
标识
DOI:10.1016/j.biopsych.2020.12.015
摘要

BackgroundFindings 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).MethodsWe 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.ResultsGSMR applied to the International Genomics of Alzheimer's Project dataset revealed a significant effect of high SBP lowering the risk of AD (βGSMR = −0.19, p = .04). GSMR applied to the maternal family history of AD UK Biobank dataset (SBP [βGSMR = −0.12, p = .02], DBP [βGSMR = −0.10, p = .05]) and to the paternal family history of AD UK Biobank dataset (SBP [βGSMR = −0.16, p = .02], DBP [βGSMR = −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 (βGSMR = −0.14, p = .03). The DBP analysis in the combined meta-analysis also confirmed a DBP effect on AD (βGSMR = −0.14, p = .03).ConclusionsA 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.
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