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Integrative Multi-Omics Mendelian Randomization Highlights Causal Autophagy-Related Genes for Amyotrophic Lateral Sclerosis - PubMed

4 hours ago
  • #Amyotrophic lateral sclerosis
  • #Autophagy dysregulation
  • #Mendelian randomization
  • This study uses integrative multi-omics Mendelian randomization to identify causal autophagy-related genes for ALS.
  • Four autophagy-related genes (FNBP1, IDUA, C9orf72, USP35) show causal links to ALS risk, with varying effects in brain and blood tissues.
  • FNBP1 splicing in the brain and USP35 expression in blood are associated with higher ALS risk; IDUA methylation in brain and C9orf72 methylation in blood are linked to lower risk.
  • Additional analyses highlight astrocytes as key brain cells, interactions with genes like SQSTM1 and PFN1, and suggest druggability for FNBP1 in ALS.