A genomic pathway approach to a complex disease: Axon guidance and Parkinson disease

2007

Genomic Pathway Approach to Parkinson Disease

Sample size: 443 publication 10 minutes Evidence: high

Author Information

Author(s): Lesnick Timothy G, Papapetropoulos Spiridon, Mash Deborah C, Ffrench-Mullen Jarlath, Shehadeh Lina, de Andrade Mariza, Henley John R, Rocca Walter A, Ahlskog J. Eric, Maraganore Demetrius M

Primary Institution: Mayo Clinic College of Medicine

Hypothesis

Does polymorphism in the axon guidance pathway predispose individuals to Parkinson disease?

Conclusion

The study found that multiple SNPs in axon-guidance pathway genes are strong predictors of Parkinson disease susceptibility, survival free of the disease, and age at onset.

Supporting Evidence

Models constructed from axon guidance SNPs predicted PD susceptibility with an odds ratio of 90.8.
Models predicted survival free of PD with a hazards ratio of 19.0.
Models predicted age at onset of PD with an R² of 0.68.
Findings were validated using a second whole-genome association dataset.
Many axon-guidance pathway genes were differentially expressed in PD cases compared to controls.

Takeaway

This study shows that certain genes involved in guiding brain connections can affect the risk and timing of developing Parkinson's disease.

Methodology

The study used bioinformatic methods to mine a whole-genome association dataset for SNPs within axon-guidance pathway genes and constructed predictive models for PD outcomes.