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Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease
- Source :
- Neurobiology of Aging, 48, 222.e1-222.e7. Elsevier Inc., Neurobiology of aging 48, 222.e1-222.e7 (2016). doi:10.1016/j.neurobiolaging.2016.07.013, Lubbe, S J, Escott-Price, V, Brice, A, Gasser, T, Pittman, A M, Bras, J, Hardy, J, Heutink, P, Wood, N M, Singleton, A B, Grosset, D G, Carroll, C B, Law, M H, Demenais, F, Iles, M M, Bishop, D T, Newton-Bishop, J, Williams, N M & Morris, H R 2016, ' Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease ', Neurobiology of Aging, vol. 48, pp. 222.e1-222.e7 . https://doi.org/10.1016/j.neurobiolaging.2016.07.013, Neurobiology of Aging
- Publication Year :
- 2016
-
Abstract
- A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis.
- Subjects :
- Skin Neoplasms
Receptor, ErbB-4
Parkinson's
Dopamine
genetics [Receptor, ErbB-4]
Cohort Studies
genetics [Membrane Glycoproteins]
genetics [Parkinson Disease]
Genetic Report Abstract
genetics [Genetic Predisposition to Disease]
Melanoma
biosynthesis [Dopamine]
Membrane Glycoproteins
Pigmentation
Monophenol Monooxygenase
Parkinson Disease
DCC Receptor
genetics [Genetic Variation]
biosynthesis [Melanins]
genetics [Receptors, Cell Surface]
Tyrosinase
neuromelanin
Oxidoreductases
Cutaneous malignant melanoma
Ubiquitin Thiolesterase
Risk
Genotype
Neuroscience(all)
Clinical Neurology
Receptors, Cell Surface
ERBB4 protein, human
genetics [Skin Neoplasms]
genetics [Ubiquitin Thiolesterase]
genetics [Tumor Suppressor Proteins]
BAP1 protein, human
Humans
Genetic Predisposition to Disease
ddc:610
Genetic Association Studies
Melanins
genetics [Oxidoreductases]
Tumor Suppressor Proteins
DCC protein, human
Genetic Variation
genetics [Pigmentation]
Ageing
Shared genetic background
genetics [Melanoma]
RC0321
Geriatrics and Gerontology
TYRP1 protein, human
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 01974580
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging, 48, 222.e1-222.e7. Elsevier Inc., Neurobiology of aging 48, 222.e1-222.e7 (2016). doi:10.1016/j.neurobiolaging.2016.07.013, Lubbe, S J, Escott-Price, V, Brice, A, Gasser, T, Pittman, A M, Bras, J, Hardy, J, Heutink, P, Wood, N M, Singleton, A B, Grosset, D G, Carroll, C B, Law, M H, Demenais, F, Iles, M M, Bishop, D T, Newton-Bishop, J, Williams, N M & Morris, H R 2016, ' Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease ', Neurobiology of Aging, vol. 48, pp. 222.e1-222.e7 . https://doi.org/10.1016/j.neurobiolaging.2016.07.013, Neurobiology of Aging
- Accession number :
- edsair.pmid.dedup....12e981e2f5e4a5676e8263194ebea1d1