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Genetic Modifiers in Neurodegeneration.

Nimansha Jain1, Alice S Chen-Plotkin1

  • 1Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

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|July 7, 2018
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Summary
This summary is machine-generated.

Genetic modifiers significantly impact neurodegenerative diseases like Alzheimer's Disease (AD) and Parkinson's Disease (PD). Understanding these genetic influences offers new insights into polygenic disease landscapes.

Keywords:
APOEAlzheimer’s DiseaseFTLDGenetic modifierParkinson’s DiseaseTMEM106Bneurodegeneration

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Area of Science:

  • Neurogenetics
  • Genomics
  • Molecular Biology

Background:

  • Neurodegenerative diseases are increasingly understood through polygenic contributions to risk, moving beyond single-locus effects.
  • Genetic modifiers play a crucial role in disease progression and presentation.
  • The gene TMEM106B has emerged as a significant genetic modifier in Frontotemporal Lobar Degeneration (FTLD).

Purpose of the Study:

  • To review existing evidence on genetic modifier effects in major neurodegenerative diseases.
  • To explore the role of genetic modifiers in Huntington's Disease (HD), Frontotemporal Lobar Degeneration (FTLD), Alzheimer's Disease (AD), and Parkinson's Disease (PD).

Main Methods:

  • Literature review of studies investigating genetic modifier effects.
  • Analysis of genetic cohort studies and mechanistic pathway examinations.
  • Synthesis of findings related to specific genes like TMEM106B and their targets (e.g., GRN, C9orf72).

Main Results:

  • Evidence for genetic modifier effects was found across HD, FTLD, AD, and PD.
  • The gene TMEM106B demonstrates significant modifier effects on genes associated with FTLD.
  • Studies highlight the interplay between specific genes and broader polygenic contributions to disease risk.

Conclusions:

  • Genetic modifiers are integral to understanding the complex genetic architecture of neurodegenerative diseases.
  • Reported genetic modifier effects provide valuable insights into the polygenic landscape of HD, FTLD, AD, and PD.
  • Further research into genetic modifiers can illuminate disease mechanisms and inform therapeutic strategies.