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Systematic identification of modifiable risk factors and drug repurposing options for Alzheimer's disease: Mendelian randomization analyses

Wu, C.; Wu, L.; Wang, J.; Lin, L.; Li, Y.; Lu, Q.; Deng, H.-W.

2020-07-16 neurology
10.1101/2020.07.14.20153726 medRxiv
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IntroductionSeveral Mendelian randomization studies have been conducted, which identified multiple risk factors for Alzheimers disease (AD). However, they typically focus on a few pre-selected risk factors. MethodsTwo-sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1,054 risk factors/medical conditions and 28 drugs with the risk of late- onset AD. To correct for multiple comparisons, the false discovery rate was set at <0.05. ResultsThere were strong evidence of a causal association between glioma risk, reduced trunk fat-free mass, lower education levels, lower intelligence and a higher risk of AD. For 28 investigated treatments (such as antihypertensive drugs), we found limited evidence for their associations. ConclusionMR found robust evidence of causal associations between glioma, trunk fat-free and AD. Our study also confirms that higher educational attainment and higher intelligence are associated with a reduced risk of AD.

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