| Title: | High Blood Pressure and Risk of Dementia: A Two-Sample Mendelian Randomization Study in the UK Biobank |
| Journal: | Biological Psychiatry |
| Published: | 27 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33766239/ |
| DOI: | https://doi.org/10.1016/j.biopsych.2020.12.015 |
| URL: | http://www.biologicalpsychiatryjournal.com/article/S0006322320321466/pdf |
Publication 5133
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Abstract
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).</p>
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.</p>
RESULTS: GSMR 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).</p>
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.</p>
7 Keywords
- Biological Specimen Banks
- Blood Pressure
- Genome-Wide Association Study
- Humans
- Hypertension
- Mendelian Randomization Analysis
- United Kingdom
10 Authors
- William Sproviero
- Laura Winchester
- Danielle Newby
- Marco Fernandes
- Liu Shi
- Sarah M Goodday
- Albert Prats-Uribe
- Daniel P Alhambra
- Noel J Buckley
- Alejo J Nevado-Holgado
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