High blood pressure and risk of dementia: A two-sample mendelian randomization study in the UK biobank

Sproviero, W; Winchester, L; Newby, D; Goodday, S; Shi, L; Prieto Alhambra, D; Prats Uribe, A; Fernandes, M; Buckley, N; Nevado-Holgado, AJ

Journal article

High blood pressure and risk of dementia: A two-sample mendelian randomization study in the UK biobank

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 (SBP) and/or diastolic (DBP) blood pressure 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 Studies meta-analysis of 299,024 individuals of SBP or DBP as exposure variables against three different outcomes: (1) AD diagnosis (IGAP), (2) maternal (MFH-UKBB) and (3) paternal (PFH-UKBB) family history of AD. Finally, a combined meta-analysis of 368,440 individuals that included these three summary statistics was used as final outcome (MA-AD).

Results:
GSMR applied to IGAP revealed a significant effect of high SBP lowering the risk of AD (bGSMR = -0.19; p = .04). GSMR applied to MFH-UKBB (SBP, bGSMR = -0.12, p = .02; DBP, bGSMR = -0.10, p = .05) and to PFH-UKBB (SBP, bGSMR = -0.16; p = .02; DBP, bGSMR = -0.24, p = 7.4 x 10-4) showed the same effect. A subsequent meta-analysis (MA-AD) confirmed the overall significant effect for the other SBP analyses (bGSMR = -0.14, p = .03). The DBP analysis in the MA-AD also confirmed a DBP effect on AD (bGSMR = -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.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Sproviero, W., Winchester, L., Newby, D., Goodday, S., Shi, L., Prieto Alhambra, D., Prats Uribe, A., Fernandes, M., Buckley, N., & Nevado-Holgado, A. J. (2020). High blood pressure and risk of dementia: A two-sample mendelian randomization study in the UK biobank. Biological Psychiatry, 89(8), 817–824.

MLA Style

Sproviero, W., et al. “High Blood Pressure and Risk of Dementia: A Two-Sample Mendelian Randomization Study in the UK Biobank.” Biological Psychiatry, vol. 89, no. 8, Elsevier, 2020, pp. 817–24.

Chicago Style

Sproviero, W, L Winchester, D Newby, S Goodday, L Shi, D Prieto Alhambra, A Prats Uribe, M Fernandes, N Buckley, and AJ Nevado-Holgado. 2020. “High Blood Pressure and Risk of Dementia: A Two-Sample Mendelian Randomization Study in the UK Biobank.” Biological Psychiatry 89 (8): 817–24.
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