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SCIENTIFIC LITERATURE · PPR

Multicomponent Mendelian randomization and machine learning studies of potential drug targets for neurodegenerative diseases

· 2025-04-18

DOI: 10.21203/rs.3.rs-5848172/v1

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Research overview

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Abstract Neurodegenerative diseases (NDDs) remain a global health challenge. Alzheimer's disease (AD) and Parkinson's disease (PD) are the main types of NDDs worldwide, and Mendelian Randomization (MR) analysis across multi-omics and the entire genome offers novel strategies for identifying potential drug targets. This study used MR and summary-based MR(SMR) analysis to explore the causal relationship between genes and NDDs. Colocalization analysis and machine learning further validated and reinforced the MR findings. The pharmacological activity of candidate drug targets was confirmed via molecular docking and Molecular dynamics. This study revealed 14 genes that were closely associated with both NDDs. Specifically, IQCE(AD), HDHD2(AD), COMMD10(AD), ALPP (AD), FXYD6 (AD), STK3 (PD), LHFPL2 (PD), and ENPP4 (PD) were identified as risk factors for NDDs (OR > 1), whereas HEXIM2 (AD), TSC22D4 (AD), CHRNB1 (PD), BAG4 (PD), SLC25A1 (PD), and IL15 (PD) were protective factors (OR 

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