Cytogenetic location: 1q32 Genomic coordinates (GRCh38) : 1:198,700,001-214,400,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q32 | {Parkinson disease 16} | 613164 | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
Satake et al. (2009) performed a large genomewide association study in the Japanese population involving a discovery cohort of 1,078 patients with Parkinson disease and 2,628 controls followed by replication in 612 cases and 14,139 controls and second replication in 321 cases and 1,614 controls. They identified 2 novel susceptibility loci with genomewide significance on chromosomes on 1q32, designated PARK16, and 4p15. On chromosome 1q32, rs947211 showed the strongest association with PD (p = 1.52 x 10(-12), odds ratio (OR) = 1.30). This SNP is located 8.5 kb upstream of RAB7L1 (603949) and 5.6 kb downstream of SLC41A1 (610801). SNPs with significant associations to PD were found to lie within several linkage disequilibrium blocks containing 5 genes: SLC45A3 (605097), NUCKS1 (611912), RAB7L1, SLC41A1, and PM20D1 (617124). NUCKS1, RAB7L1, and SLC41A1 were contained in the same linkage disequilibrium block. The results suggested that the PARK16 locus has multiple independent association signals. Satake et al. (2009) also found strong associations with the SNCA gene (163890) on 4q22 (p = 7.35 x 10(-17)) and the LRRK2 gene (609007) on 12q12 (p = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism (PARK1, 168601 and PARK8, 607060, respectively).
Simon-Sanchez et al. (2009) performed genomewide association studies in 1,713 individuals of European ancestry with PD and 3,978 controls, followed by replication in 3,361 cases and 4,573 controls. In collaboration with Satake et al. (2009), Simon-Sanchez et al. (2009) replicated the effect of the PARK16 locus (rs823128, OR = 0.66, p = 7.29 x 10(-8)), and found supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, p = 1.55 x 10(-5)). However, association with the putative locus on 4p15 was not found in the European population. Overall, the data from both studies showed a role for common genetic variants in the etiology of typical PD, and suggested population-specific genetic heterogeneity in this disease. Simon-Sanchez et al. (2009) also identified association signals in the SNCA gene (rs2736990, OR = 1.23, p = 2.24 x 10(-16)) and the MAPT gene (157140) on 17q21 (rs393152, OR = 0.77, p = 1.95 x 10(-16)).
Tan et al. (2010) specifically analyzed 5 SNPs at the PARK16 locus in 433 PD patients and 916 controls, all of Chinese ethnicity. Significant disease associations were found for 3 SNPS: rs11240572, rs823128, and rs823156 with the most significant association at rs823156 (corrected p = 0.0161; OR, 0.77). However, rs16856139 and rs947211 failed to reach significance.
Vilarino-Guell et al. (2010) replicated the association between Parkinson disease and rs823128 in a cohort of 315 Taiwanese patients and 247 Taiwanese controls (p = 0.015). However, the association with this SNP was not significant in patients of European origin or those from Tunisia.
Mata et al. (2011) failed to find an association between rs823156 or rs947211 on chromosome 1q32 in a case-control study of 1,445 PD patients and 1,161 controls from northern Spain.
Associations Pending Confirmation
For discussion of a possible association between early-onset Parkinson disease with cognitive dysfunction and variation in the ADORA1 gene on chromosome 1q32, see 102775.0001.
Mata, I. F., Yearout, D., Alvarez, V., Coto, E., de Mena, L., Ribacoba, R., Lorenzo-Betancor, O., Samaranch, L., Pastor, P., Cervantes, S., Infante, J., Garcia-Gorostiaga, I., Sierra, M., Combarros, O., Snapinn, K. W., Edwards, K. L., Zabetian, C. P. Replication of MAPT and SNCA, but not PARK16-18, as susceptibility genes for Parkinson's disease. Mov. Disord. 26: 819-823, 2011. [PubMed: 21425343] [Full Text: https://doi.org/10.1002/mds.23642]
Satake, W., Nakabayashi, Y., Mizuta, I., Hirota, Y., Ito, C., Kubo, M., Kawaguchi, T., Tsunoda, T., Watanabe, M., Takeda, A., Tomiyama, H., Nakashima, K., and 10 others. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. (Letter) Nature Genet. 41: 1303-1307, 2009. [PubMed: 19915576] [Full Text: https://doi.org/10.1038/ng.485]
Simon-Sanchez, J., Schulte, C., Bras, J. M., Sharma, M., Gibbs, J. R., Berg, D., Paisan-Ruiz, C., Lichtner, P., Scholz, S. W., Hernandez, D. G., Kruger, R., Federoff, M., and 35 others. Genome-wide association study reveals genetic risk underlying Parkinson's disease. (Letter) Nature Genet. 41: 1308-1312, 2009. [PubMed: 19915575] [Full Text: https://doi.org/10.1038/ng.487]
Tan, E.-K., Kwok, H.-H., Tan, L. C., Zhao, W.-T., Prakash, K. M., Au, W.-L., Pavanni, R., Ng, Y.-Y., Satake, W., Zhao, Y., Toda, T., Liu, J.-J. Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus. Neurology 75: 508-512, 2010. Note: Erratum: Neurology 75: 1399 only, 2010. [PubMed: 20697102] [Full Text: https://doi.org/10.1212/WNL.0b013e3181eccfcd]
Vilarino-Guell, C., Ross, O. A., Aasly, J. O., White, L. R., Rajput, A., Rajput, A. H., Lynch, T., Krygowska-Wajs, A., Jasinska-Myga, B., Opala, G., Barcikowska, M., Lee, M.-C., Hentati, F., Uitti, R. J., Wszolek, Z. K., Farrer, M. J., Wu, R.-M. An independent replication of PARK16 in Asian samples. Neurology 75: 2248-2249, 2010. [PubMed: 21172849] [Full Text: https://doi.org/10.1212/WNL.0b013e318202031f]