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The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study and Literature Review - PubMed

4 hours ago
  • #biomarker
  • #genetics
  • #neurodegeneration
  • Four common variants in ANXA11 (rs113772135, rs2789686, rs1079242, rs61860017) were significantly associated with TDP-C and replicated in independent cohorts.
  • Rs1079242-A showed the strongest replication and correlates with higher ANXA11 levels in CSF, suggesting potential as a CSF biomarker.
  • No significant associations were found between TARDBP variants and TDP-C.
  • AI-guided rare variant analysis identified a pathogenic variant in FIG4, a gene linked to ALS.
  • Mendelian randomization indicated that ALS genetic load is associated with increased TDP-C risk, hinting at a genetic overlap.
  • ANXA11 and FIG4 are both involved in the inositol pathway, offering new mechanistic insights into TDP-C.