Details

Autor(en) / Beteiligte

• Sproviero, William
• Winchester, Laura
• Newby, Danielle
• Fernandes, Marco
• Shi, Liu
• Goodday, Sarah M.
• Prats-Uribe, Albert
• Alhambra, Daniel P.
• Buckley, Noel J.
• Nevado-Holgado, Alejo J.

Titel

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

Ist Teil von

• Biological psychiatry (1969), 2021-04, Vol.89 (8), p.817-824

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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). 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. 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). 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.