Parkinson's disease

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Wikipedia is a good start for those looking for general information about Parkinson's disease, including in the Genetic section.

Many SNPs have been reported to be associated with Parkinson's disease risk, but few have shown significant odds or have been robustly replicated.

To date, the most common genetic risk factor for Parkinson's disease are mutations in the GBA gene; overall, mutations like rs35095275, also known as L444P, appear to increase the odds of developing Parkinson's disease by at least 5 fold. They also lower the age of onset by about 4 years, and influence risk across all ethnicities studied.[PMID 19846850]


Non-GBA related reports of single SNP associations include:

  • Several variations in the GSTP1 gene, which encodes a detoxification enzyme, have been linked to earlier onset of Parkinson's disease, especially in patients exposed to herbicides. [PMID 17190945]
  • TNF-alpha promoter polymorphism is associated with the risk of Parkinson's disease. [PMID 17192953]
  • Two studies [PMID 14991823, PMID 15174030] have concluded that the risk of developing Parkinson's disease upon exposure to pesticides is increased from 3 to 8 fold among carriers of CYP2D6*4 (rs3892097(A)) alleles. The risk to CYP2D6*4 carriers appears proportional to the degree of pesticide exposure, with no additional risk of developing Parkinson's seen for CYP2D6*4 carriers with no pesticide exposure, and the highest increased risk of developing Parkinson's seen for CYP2D6*4 carriers with frequent exposure to pesticides.
  • Risk alleles defined by several SNPs in the SLC6A3 gene, encoding a dopamine transporter, have been associated with increased risk for Parkinson's. With pesticide exposure, the risk associated with these alleles is 6X higher. [PMID 16963468]
  • [PMID 18162487] rs356219 a tagging SNP for a Parkinson's disease haplotype the "protective" genotype 259/259 of the repeat NACP-Rep1 is associated with lower protein levels in blood than genotypes 261/261, 259/261, and 259/263
  • [PMID 18663495] Various SNPs in the NOS1 and NOS2A genes were somewhat associated with sporadic Parkinson's disease and/or age of onset, with a subset also interacting with either smoking or pesticides.
  • [PMID 18075470] Parkinson's disease (P=0.08). A significant association was seen between caffeine intake and the onset of PD (P=2.01×10(-5)), with the odds ratio for moderate and high drinkers at 0.71 [95% confidence interval (CI): 0.50-1.00] and 0.47 (95% CI: 0.34-0.65), respectively against the low drinkers.


Note that a 2006 survey of many common genetic variations that may be related to PD [3] has been publicly released; the conclusion at that time was that no single SNP (from 400,00 on Illumina microarrays) was statistically significant enough to indicate (by itself) increased risk of Parkinson's [PMID 17052657].


A 2007 report indicates that models built up from combinations of variations (ie SNPs) in 'axon guidance pathway' genes can robustly score Parkinson's susceptibility (including age of onset).[PMID 17571925] A follow up study published in January 2008 presents a model combining ~50 SNPs from genes in axon guidance pathways said to predict susceptibility to Parkinson's disease, survival free of Parkinson's, and age of onset.10.1371/journal.pone.0001449; Medpage news article However, an independent 2008 study to replicate this not only did not, but reported that SNPs from randomly chosen genes fit to a model using similar methods seemed to give just as significant results as SNPs from axon guidance genes. In other words, the model was deemed highly "overfitted", calling all the results into question.[PMID 18628988]

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