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Home › Research › Prevention and risk

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

Lesnick TG, Papapetropoulos S, Mash DC, Ffrench-Mullen J, Shehadeh L, de Andrade M, Henley JR, Rocca WA et al.. PLoS genetics, 2007-06-01

This page is alzhub.org's plain-English summary of a published study, not the paper itself. It is generated from the record we hold for this study, sourced and linked below — check the original for the full text and methods.

✓ Peer-reviewed alzhub usefulness score 40 out of 100. Prevention and risk

Topic: Genetics and APOE

While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics). The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance) predisposed to a complex disease (Parkinson disease [PD]). We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs) that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38)), survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48)), and PD age at onset (R(2) = 0.68, p = 1.68 x 10(-51)). By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

Key findings

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Study details

How this study scored 40/100
How this study's score is builtJournal tier 7 of 10; Journal's citation record left out, no data; Study design 0 of 12; Strength of evidence 1 of 5; Peer-review validation 10 of 10; How recent 1 of 5; Sample size 0 of 4; Effect reported 0 of 3; Studied in people 0 of 3; Randomised / blinded 0 of 2; Times cited left out, no data; Citations per year left out, no data; Impact for its field and year left out, no data; Cited by studies here left out, no data; Still being cited left out, no data; Senior author's track record left out, no data; Institution's track record left out, no data; Multi-centre collaboration left out, no data; Indexed in PubMed 2 of 2; Free to read 2 of 2. 23 of the 58 points it could be judged on, which is 40 of 100. Total 40 of 100.23 of the 58 points we could judge = 40 of 100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.

ComponentPointsWhy
Journal tier 7 / 10 Tier 3 — peer-reviewed journal (PLoS genetics)
Journal's citation record — / 4 No journal record from OpenAlex — left out of this score
Study design 0 / 12 No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence 1 / 5 Rated “low” in our summary
Peer-review validation 10 / 10 Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent 1 / 5 2007 — within 20 year(s) of the newest study here
Sample size 0 / 4 Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported 0 / 3 No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people 0 / 3 Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomised / blinded 0 / 2 No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited — / 7 No citation count (not found in OpenAlex) — left out of this score
Citations per year — / 5 No citation count or no year — left out of this score
Impact for its field and year — / 6 No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here — / 6 Not yet checked against this library's citation graph — left out of this score
Still being cited — / 4 No yearly citation counts — left out of this score
Senior author's track record — / 4 Senior author's record not available — left out of this score
Institution's track record — / 3 No institution listed in OpenAlex — left out of this score
Multi-centre collaboration — / 3 Institutions not listed — left out of this score
Indexed in PubMed 2 / 2 Indexed in PubMed (PMID 17571925)
Free to read 2 / 2 Free to read
Points 23 / 58 Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100.
Total 40 / 100 —

What each of these 20 components measures, and what this score is not →

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APA 7th

Lesnick, T. G., Papapetropoulos, S., Mash, D. C., Ffrench-Mullen, J., Shehadeh, L., de Andrade, M., et al. (2007). A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS genetics. https://doi.org/10.1371/journal.pgen.0030098

Vancouver

Lesnick TG, Papapetropoulos S, Mash DC, Ffrench-Mullen J, Shehadeh L, de Andrade M, et al. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS genetics. 2007. doi:10.1371/journal.pgen.0030098. PMID: 17571925.

BibTeX

@article{lesnick2007-17571925,
  author  = {Lesnick, T. G. and Papapetropoulos, S. and Mash, D. C. and Ffrench-Mullen, J. and Shehadeh, L. and de Andrade, M. and Henley, JR. and Rocca, W. A. and others},
  title   = {{A genomic pathway approach to a complex disease: axon guidance and Parkinson disease}},
  journal = {PLoS genetics},
  year    = {2007},
  doi     = {10.1371/journal.pgen.0030098},
  pmid    = {17571925},
  url     = {https://doi.org/10.1371/journal.pgen.0030098}
}

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