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Detecting potential causal relationship between multiple risk factors and Alzheimer's disease using multivariable Mendelian randomization.

ABSTRACT: BACKGROUND:Alzheimer's disease (AD) is a progressive brain disorder characterized by cognitive skills deterioration that affects many elderly individuals. The identified genetic loci for AD failed to explain the large variability in AD and very few causal factors have been identified so far. RESULTS:mvMR showed that increasing years of schooling (OR=0.674, 95%CI: 0.571-0.796, P=3.337E-06) and genetically elevated HDL cholesterol (OR ranging from 0.697 to 0.830, P=6.940E-10) were inversely associated with AD risk, genetically predicted total cholesterol (OR=1.300, 1.196 to 1.412; P=6.223E-10) and LDL cholesterol (OR=1.193, 1.097 to 1.296, P=3.564E-05) were associated with increasing AD risk. Genetically predicted FG was suggestively associated with increased AD risk. Furthermore, MR-BMA analysis also confirmed FG and years of schooling as two of the top five causal risk factors for AD. CONCLUSIONS:Our findings might provide us novel insights for treatment and intervention into the causal risk factors for AD or AD-related complex diseases. METHODS:By using extension methods of Mendelian randomization (MR)--multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA), we intend to estimate the potential causal relationship between nine risk factors and AD outcome and try to prioritize the most causal risk factors for AD.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC7695397 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Detecting potential causal relationship between multiple risk factors and Alzheimer's disease using multivariable Mendelian randomization.

Zhang Qiang Q Xu Fei F Wang Lianke L Zhang Wei-Dong WD Sun Chang-Qing CQ Deng Hong-Wen HW

Aging 20201107 21

<h4>Background</h4>Alzheimer's disease (AD) is a progressive brain disorder characterized by cognitive skills deterioration that affects many elderly individuals. The identified genetic loci for AD failed to explain the large variability in AD and very few causal factors have been identified so far.<h4>Results</h4>mvMR showed that increasing years of schooling (OR=0.674, 95%CI: 0.571-0.796, <i>P</i>=3.337E-06) and genetically elevated HDL cholesterol (OR ranging from 0.697 to 0.830, <i>P</i>=6.9 ...[more]

PMID: 33177243

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Detecting potential causal relationship between multiple risk factors and Alzheimer's disease using multivariable Mendelian randomization.

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Detecting potential causal relationship between multiple risk factors and Alzheimer's disease using multivariable Mendelian randomization.

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