TY - JOUR
T1 - High blood pressure and risk of dementia
T2 - a two-sample Mendelian randomization study in the UK biobank
AU - Sproviero, William
AU - Winchester, Laura
AU - Newby, Danielle
AU - Fernandes, Marco
AU - Shi, Liu
AU - Goodday, Sarah M.
AU - Prats-Uribe, Albert
AU - Alhambra, Daniel P.
AU - Buckley, Noel J.
AU - Nevado-Holgado, Alejo J.
N1 - This work was supported by Janssen Research and Development , LLC (of Johnson & Johnson).
PY - 2021/4/15
Y1 - 2021/4/15
N2 - 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 (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). 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.
AB - 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 (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). 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.
KW - Alzheimer's disease
KW - Blood pressure
KW - Family history of Alzheimer's disease
KW - Genetic variants
KW - Mendelian randomization
U2 - 10.1016/j.biopsych.2020.12.015
DO - 10.1016/j.biopsych.2020.12.015
M3 - Article
C2 - 33766239
AN - SCOPUS:85102583040
SN - 0006-3223
VL - 89
SP - 817
EP - 824
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 8
ER -