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Bidirectional relationship between olfaction and Parkinson's disease.

Jonggeol Jeffrey Kim1,2, Sara Bandres-Ciga3, Karl Heilbron4,5

  • 1Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.

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Summary

Parkinson's disease (PD) is linked to decreased smell (hyposmia). Genetic analysis reveals a shared genetic basis, with PD causally influencing smell ability, highlighting olfactory function

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Area of Science:

  • Genetics
  • Neuroscience
  • Olfactory Research

Background:

  • Hyposmia (decreased smell) is a frequent early indicator of Parkinson's disease (PD).
  • The genetic underpinnings connecting hyposmia and PD remain largely unexplored.
  • Understanding this genetic link is crucial for early PD detection and therapeutic strategies.

Purpose of the Study:

  • To investigate the shared genetic architecture between olfactory function and Parkinson's disease.
  • To determine the directionality of any causal relationship between hyposmia and PD.

Main Methods:

  • Utilized genome-wide association study (GWAS) data for self-reported smell ability and PD diagnosis.
  • Employed Linkage Disequilibrium Score (LDSC) regression to assess genome-wide genetic correlation.
  • Applied Local Analysis of [co]Variant Association (LAVA) and Mendelian randomization (MR) for fine-mapping and causal inference.

Main Results:

  • A significant negative genome-wide genetic correlation was observed between the sense of smell and PD.
  • Four genetic loci (near GBA1, ANAPC4, SNCA, MAPT) showed significant negative correlations, implicating specific PD risk genes.
  • Mendelian randomization indicated a strong causal effect of PD on hyposmia, with a weaker reverse causal effect.

Conclusions:

  • Olfactory function and Parkinson's disease share significant genetic liability.
  • Parkinson's disease appears to causally influence the decline in sense of smell.
  • This study underscores the heritability of olfactory function and its intricate relationship with PD pathogenesis.