Beyond Parkinson disease: Amyotrophic lateral sclerosis and the Axon guidance pathway

Timothy G. Lesnick, Eric J. Sorenson, J. Eric Ahlskog, John R. Henley, Lina Shehadeh, Spiridon Papapetropoulos, Demetrius M. Maraganore

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background. We recently described a genomic pathway approach to study complex diseases. We demonstrated that models constructed using single nucleotide polymorphisms (SNPs) within axon guidance pathway genes were highly predictive of Parkinson disease (PD) susceptibility, survival free of PD, and age at onset of PD within two independent whole-genome association datasets. We also demonstrated that several axon guidance pathway genes represented by SNPs within our final models were differentially expressed in PD. Methodology/Principal Findings. Here we employed our genomic pathway approach to analyze data from a whole-genome association dataset of amyotrophic lateral sclerosis (ALS); and demonstrated that models constructed using SNPs within axon guidance pathway genes were highly predictive of ALS susceptibility (odds ratio = 1739.73, p=2.92×10-60), survival free of ALS (hazards ratio = 149.80, p=1.25×10-74), and age at onset of ALS (R2=0.86, P=5.96×10-66). We also extended our analyses of a whole-genome association dataset of PD, which shared 320,202 genomic SNPs in common with the whole-genome association dataset of ALS. We compared for ALS and PD the genes represented by SNPs in the final models for susceptibility, survival free of disease, and age at onset of disease and noted that 52.2%, 37.8%, and 34.9% of the genes were shared respectively. Conclusion/Significant: Our findings for the axon guidance pathway and ALS have prior biological plausibility, overlap partially with PD, and may provide important insight into the causes of these and related neurodegenerative disorders.

Original languageEnglish
Article numbere1449
JournalPLoS One
Volume3
Issue number1
DOIs
StatePublished - Jan 16 2008

Fingerprint

Parkinson disease
Amyotrophic Lateral Sclerosis
axons
Parkinson Disease
Genes
single nucleotide polymorphism
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
genome
Genome
genomics
Age of Onset
genes
Genome-Wide Association Study
Disease Susceptibility
neurodegenerative diseases
Axon Guidance
amyotrophic lateral sclerosis
Axons

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lesnick, T. G., Sorenson, E. J., Ahlskog, J. E., Henley, J. R., Shehadeh, L., Papapetropoulos, S., & Maraganore, D. M. (2008). Beyond Parkinson disease: Amyotrophic lateral sclerosis and the Axon guidance pathway. PLoS One, 3(1), [e1449]. https://doi.org/10.1371/journal.pone.0001449

Beyond Parkinson disease : Amyotrophic lateral sclerosis and the Axon guidance pathway. / Lesnick, Timothy G.; Sorenson, Eric J.; Ahlskog, J. Eric; Henley, John R.; Shehadeh, Lina; Papapetropoulos, Spiridon; Maraganore, Demetrius M.

In: PLoS One, Vol. 3, No. 1, e1449, 16.01.2008.

Research output: Contribution to journalArticle

Lesnick, TG, Sorenson, EJ, Ahlskog, JE, Henley, JR, Shehadeh, L, Papapetropoulos, S & Maraganore, DM 2008, 'Beyond Parkinson disease: Amyotrophic lateral sclerosis and the Axon guidance pathway', PLoS One, vol. 3, no. 1, e1449. https://doi.org/10.1371/journal.pone.0001449
Lesnick TG, Sorenson EJ, Ahlskog JE, Henley JR, Shehadeh L, Papapetropoulos S et al. Beyond Parkinson disease: Amyotrophic lateral sclerosis and the Axon guidance pathway. PLoS One. 2008 Jan 16;3(1). e1449. https://doi.org/10.1371/journal.pone.0001449
Lesnick, Timothy G. ; Sorenson, Eric J. ; Ahlskog, J. Eric ; Henley, John R. ; Shehadeh, Lina ; Papapetropoulos, Spiridon ; Maraganore, Demetrius M. / Beyond Parkinson disease : Amyotrophic lateral sclerosis and the Axon guidance pathway. In: PLoS One. 2008 ; Vol. 3, No. 1.
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