Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2009

Open Access 01-12-2009 | Research article

Genomewide association study for onset age in Parkinson disease

Authors: Jeanne C Latourelle, Nathan Pankratz, Alexandra Dumitriu, Jemma B Wilk, Stefano Goldwurm, Gianni Pezzoli, Claudio B Mariani, Anita L DeStefano, Cheryl Halter, James F Gusella, William C Nichols, Richard H Myers, Tatiana Foroud, the PSG -PROGENI and GenePD Investigators, Coordinators and Molecular Genetic Laboratories

Published in: BMC Medical Genetics | Issue 1/2009

Login to get access

Abstract

Background

Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age.

Methods

Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy.

Results

Meta-analysis across the three studies detected consistent association (p < 1 × 10-5) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 × 10-7) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 × 10-6) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases.

Conclusion

Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis.
Appendix
Available only for authorised users
Literature
1.
Mayeux R: Epidemiology of neurodegeneration. Annual review of neuroscience. 2003, 26: 81-104. 10.1146/annurev.neuro.26.043002.094919.CrossRefPubMed
2.
Schrag A, Ben-Shlomo Y, Brown R, Marsden CD, Quinn N: Young-onset Parkinson's disease revisited--clinical features, natural history, and mortality. Mov Disord. 1998, 13 (6): 885-894. 10.1002/mds.870130605.CrossRefPubMed
3.
Bower JH, Maraganore DM, McDonnell SK, Rocca WA: Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990. Neurology. 1999, 52 (6): 1214-1220.CrossRefPubMed
4.
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL: Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science (New York, NY). 1997, 276 (5321): 2045-2047.CrossRef
5.
Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998, 392 (6676): 605-608. 10.1038/33416.CrossRefPubMed
6.
Valente EM, Bentivoglio AR, Dixon PH, Ferraris A, Ialongo T, Frontali M, Albanese A, Wood NW: Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet. 2001, 68 (4): 895-900. 10.1086/319522.CrossRefPubMedPubMedCentral
7.
van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJ, Testers L, Breedveld GJ, Horstink M, Sandkuijl LA, van Swieten JC, Oostra BA, Heutink P: Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet. 2001, 69 (3): 629-634. 10.1086/322996.CrossRefPubMedPubMedCentral
8.
Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, Brug van der M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB: Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 2004, 44 (4): 595-600. 10.1016/j.neuron.2004.10.023.CrossRefPubMed
9.
Sun M, Latourelle JC, Wooten GF, Lew MF, Klein C, Shill HA, Golbe LI, Mark MH, Racette BA, Perlmutter JS, Parsian A, Guttman M, Nicholson G, Xu G, Wilk JB, Saint-Hilaire MH, DeStefano AL, Prakash R, Williamson S, Suchowersky O, Labelle N, Growdon JH, Singer C, Watts RL, Goldwurm S, Pezzoli G, Baker KB, Pramstaller PP, Burn DJ, Chinnery PF, Sherman S, Vieregge P, Litvan I, Gillis T, MacDonald ME, Myers RH, Gusella JF: Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Arch Neurol. 2006, 63 (6): 826-832. 10.1001/archneur.63.6.826.CrossRefPubMed
10.
Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C, Shults C, Marder K, Conneally PM, Nichols WC: Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology. 2003, 60 (5): 796-801.CrossRefPubMed
11.
Nichols WC, Pankratz N, Hernandez D, Paisan-Ruiz C, Jain S, Halter CA, Michaels VE, Reed T, Rudolph A, Shults CW, Singleton A, Foroud T: Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease. Lancet. 2005, 365 (9457): 410-412.PubMed
12.
Latourelle JC, Sun M, Lew MF, Suchowersky O, Klein C, Golbe LI, Mark MH, Growdon JH, Wooten GF, Watts RL, Guttman M, Racette BA, Perlmutter JS, Ahmed A, Shill HA, Singer C, Goldwurm S, Pezzoli G, Zini M, Saint-Hilaire MH, Hendricks AE, Williamson S, Nagle MW, Wilk JB, Massood T, Huskey KW, Laramie JM, Destefano AL, Baker KB, Itin I, Litvan I, Nicholson G, Corbett A, Nance M, Drasby E, Isaacson S, Burn DJ, Chinnery PF, Pramstaller PP, Al-Hinti J, Moller AT, Ostergaard K, Sherman SJ, Roxburgh R, Snow B, Slevin JT, Cambi F, Gusella JF, Myers RH: The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's Disease: the GenePD study. BMC Med. 2008, 6 (1): 32-10.1186/1741-7015-6-32.CrossRefPubMedPubMedCentral
13.
Goldwurm S, Zini M, Mariani L, Tesei S, Miceli R, Sironi F, Clementi M, Bonifati V, Pezzoli G: Evaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in Parkinson disease. Neurology. 2007, 68 (14): 1141-1143. 10.1212/01.wnl.0000254483.19854.ef.CrossRefPubMed
14.
Maher NE, Golbe LI, Lazzarini AM, Mark MH, Currie LJ, Wooten GF, Saint-Hilaire M, Wilk JB, Volcjak J, Maher JE, Feldman RG, Guttman M, Lew M, Waters CH, Schuman S, Suchowersky O, Lafontaine AL, Labelle N, Vieregge P, Pramstaller PP, Klein C, Hubble J, Reider C, Growdon J, Watts R, Montgomery E, Baker K, Singer C, Stacy M, Myers RH: Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study. Neurology. 2002, 58 (1): 79-84.CrossRefPubMed
15.
Maher NE, Currie LJ, Lazzarini AM, Wilk JB, Taylor CA, Saint-Hilaire MH, Feldman RG, Golbe LI, Wooten GF, Myers RH: Segregation analysis of Parkinson disease revealing evidence for a major causative gene. American journal of medical genetics. 2002, 109 (3): 191-197. 10.1002/ajmg.10335.CrossRefPubMed
16.
McDonnell SK, Schaid DJ, Elbaz A, Strain KJ, Bower JH, Ahlskog JE, Maraganore DM, Rocca WA: Complex segregation analysis of Parkinson's disease: The Mayo Clinic Family Study. Annals of neurology. 2006, 59 (5): 788-795. 10.1002/ana.20844.CrossRefPubMed
17.
Zareparsi S, Taylor TD, Harris EL, Payami H: Segregation analysis of Parkinson disease. American journal of medical genetics. 1998, 80 (4): 410-417. 10.1002/(SICI)1096-8628(19981204)80:4<410::AID-AJMG21>3.0.CO;2-2.CrossRefPubMed
18.
Fung HC, Scholz S, Matarin M, Simon-Sanchez J, Hernandez D, Britton A, Gibbs JR, Langefeld C, Stiegert ML, Schymick J, Okun MS, Mandel RJ, Fernandez HH, Foote KD, Rodriguez RL, Peckham E, De Vrieze FW, Gwinn-Hardy K, Hardy JA, Singleton A: Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data. Lancet neurology. 2006, 5 (11): 911-916. 10.1016/S1474-4422(06)70578-6.CrossRefPubMed
19.
Maraganore DM, de Andrade M, Lesnick TG, Strain KJ, Farrer MJ, Rocca WA, Pant PV, Frazer KA, Cox DR, Ballinger DG: High-resolution whole-genome association study of Parkinson disease. American journal of human genetics. 2005, 77 (5): 685-693. 10.1086/496902.CrossRefPubMedPubMedCentral
20.
Pankratz N, Wilk JB, Latourelle JC, DeStefano AL, Halter C, Pugh EW, Doheny KF, Gusella JF, Nichols WC, Foroud T, Myers RH: Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Human genetics. 2009, 124 (6): 593-605. 10.1007/s00439-008-0582-9.CrossRefPubMed
21.
Gibb WR, Lees AJ: The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry. 1988, 51 (6): 745-752. 10.1136/jnnp.51.6.745.CrossRefPubMedPubMedCentral
22.
Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A, Shults C, Conneally PM, Foroud T: Genome screen to identify susceptibility genes for Parkinson disease in a sample without parkin mutations. American journal of human genetics. 2002, 71 (1): 124-135. 10.1086/341282.CrossRefPubMedPubMedCentral
23.
Pankratz N, Pauciulo MW, Elsaesser VE, Marek DK, Halter CA, Rudolph A, Shults CW, Foroud T, Nichols WC: Mutations in LRRK2 other than G2019S are rare in a north American-based sample of familial Parkinson's disease. Mov Disord. 2006, 21 (12): 2257-2260. 10.1002/mds.21162.CrossRefPubMed
24.
Nichols WC, Elsaesser VE, Pankratz N, Pauciulo MW, Marek DK, Halter CA, Rudolph A, Shults CW, Foroud T: LRRK2 mutation analysis in Parkinson disease families with evidence of linkage to PARK8. Neurology. 2007, 69 (18): 1737-1744. 10.1212/01.wnl.0000278115.50741.4e.CrossRefPubMed
25.
Nichols WC, Uniacke SK, Pankratz N, Reed T, Simon DK, Halter C, Rudolph A, Shults CW, Conneally PM, Foroud T: Evaluation of the role of Nurr1 in a large sample of familial Parkinson's disease. Mov Disord. 2004, 19 (6): 649-655. 10.1002/mds.20097.CrossRefPubMed
26.
Karamohamed S, Golbe LI, Mark MH, Lazzarini AM, Suchowersky O, Labelle N, Guttman M, Currie LJ, Wooten GF, Stacy M, Saint-Hilaire M, Feldman RG, Liu J, Shoemaker CM, Wilk JB, DeStefano AL, Latourelle JC, Xu G, Watts R, Growdon J, Lew M, Waters C, Vieregge P, Pramstaller PP, Klein C, Racette BA, Perlmutter JS, Parsian A, Singer C, Montgomery E, Baker K, Gusella JF, Herbert A, Myers RH: Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2 (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from the GenePD study. Mov Disord. 2005, 20 (9): 1188-1191. 10.1002/mds.20515.CrossRefPubMed
27.
Pankratz N, Nichols WC, Elsaesser VE, Pauciulo MW, Marek DK, Halter CA, Wojcieszek J, Rudolph A, Pfeiffer RF, Foroud T: Alpha-synuclein and familial Parkinson's disease. Mov Disord. 2009, 24 (8): 1125-1131. 10.1002/mds.22524.CrossRefPubMedPubMedCentral
28.
Reider CR, Halter CA, Castelluccio PF, Oakes D, Nichols WC, Foroud T: Reliability of reported age at onset for Parkinson's disease. Mov Disord. 2003, 18 (3): 275-279. 10.1002/mds.10391.CrossRefPubMed
29.
Gunderson KL, Steemers FJ, Ren H, Ng P, Zhou L, Tsan C, Chang W, Bullis D, Musmacker J, King C, Lebruska LL, Barker D, Oliphant A, Kuhn KM, Shen R: Whole-genome genotyping. Methods in enzymology. 2006, 410: 359-376. 10.1016/S0076-6879(06)10017-8.CrossRefPubMed
30.
Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen WM, Bonnycastle LL, Shen H, Timpson N, Lettre G, Usala G, Chines PS, Stringham HM, Scott LJ, Dei M, Lai S, Albai G, Crisponi L, Naitza S, Doheny KF, Pugh EW, Ben-Shlomo Y, Ebrahim S, Lawlor DA, Bergman RN, Watanabe RM, Uda M, Tuomilehto J, Coresh J, Hirschhorn JN, Shuldiner AR, Schlessinger D, Collins FS, Davey Smith G, Boerwinkle E, Cao A, Boehnke M, Abecasis GR, Mohlke KL: Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 2008, 40 (2): 198-203. 10.1038/ng.74.CrossRefPubMedPubMedCentral
31.
Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Hercberg S, Zelenika D, Chen WM, Li Y, Scott LJ, Scheet PA, Sundvall J, Watanabe RM, Nagaraja R, Ebrahim S, Lawlor DA, Ben-Shlomo Y, Davey-Smith G, Shuldiner AR, Collins R, Bergman RN, Uda M, Tuomilehto J, Cao A, Collins FS, Lakatta E, Lathrop GM, Boehnke M, Schlessinger D, Mohlke KL, Abecasis GR: Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008, 40 (2): 161-169. 10.1038/ng.76.CrossRefPubMed
32.
Li Y, Abecasis G: Mach 1.0: Rapid Haplotype Reconstruction and Missing Genotype Inference. American journal of human genetics. 2006, S79: 2290-
33.
The International HapMap Project. Nature. 2003, 426 (6968): 789-796. 10.1038/nature02168.
34.
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007, 447 (7145): 661-678. 10.1038/nature05911.
35.
Marchini J, Howie B, Myers S, McVean G, Donnelly P: A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007, 39 (7): 906-913. 10.1038/ng2088.CrossRefPubMed
36.
Lettre G, Lange C, Hirschhorn JN: Genetic model testing and statistical power in population-based association studies of quantitative traits. Genetic epidemiology. 2007, 31 (4): 358-362. 10.1002/gepi.20217.CrossRefPubMed
37.
de Bakker PI, Ferreira MA, Jia X, Neale BM, Raychaudhuri S, Voight BF: Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet. 2008, 17 (R2): R122-128. 10.1093/hmg/ddn288.CrossRefPubMedPubMedCentral
38.
Biasiotto G, Goldwurm S, Finazzi D, Tunesi S, Zecchinelli A, Sironi F, Pezzoli G, Arosio P: HFE gene mutations in a population of Italian Parkinson's disease patients. Parkinsonism Relat Disord. 2008, 14 (5): 426-430. 10.1016/j.parkreldis.2007.10.011.CrossRefPubMed
39.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. American journal of human genetics. 2007, 81 (3): 559-575. 10.1086/519795.CrossRefPubMedPubMedCentral
40.
Risch N, Merikangas K: The future of genetic studies of complex human diseases. Science. 1996, 273 (5281): 1516-1517. 10.1126/science.273.5281.1516.CrossRefPubMed
41.
Pe'er I, Yelensky R, Altshuler D, Daly MJ: Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genetic epidemiology. 2008, 32 (4): 381-385. 10.1002/gepi.20303.CrossRefPubMed
42.
Dudbridge F, Gusnanto A: Estimation of significance thresholds for genomewide association scans. Genetic epidemiology. 2008, 32 (3): 227-234. 10.1002/gepi.20297.CrossRefPubMedPubMedCentral
43.
Lee ST, Nicholls RD, Bundey S, Laxova R, Musarella M, Spritz RA: Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. N Engl J Med. 1994, 330 (8): 529-534. 10.1056/NEJM199402243300803.CrossRefPubMed
44.
Rebbeck TR, Kanetsky PA, Walker AH, Holmes R, Halpern AC, Schuchter LM, Elder DE, Guerry D: P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev. 2002, 11 (8): 782-784.PubMed
45.
Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Palsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007, 39 (12): 1443-1452. 10.1038/ng.2007.13.CrossRefPubMed
46.
Zhu G, Evans DM, Duffy DL, Montgomery GW, Medland SE, Gillespie NA, Ewen KR, Jewell M, Liew YW, Hayward NK, Sturm RA, Trent JM, Martin NG: A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. Twin Res. 2004, 7 (2): 197-210. 10.1375/136905204323016186.CrossRefPubMed
47.
Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA: A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. American journal of human genetics. 2007, 80 (2): 241-252. 10.1086/510885.CrossRefPubMed
48.
Frudakis T, Terravainen T, Thomas M: Multilocus OCA2 genotypes specify human iris colors. Human genetics. 2007, 122 (3-4): 311-326. 10.1007/s00439-007-0401-8.CrossRefPubMed
49.
Jannot AS, Meziani R, Bertrand G, Gerard B, Descamps V, Archimbaud A, Picard C, Ollivaud L, Basset-Seguin N, Kerob D, Lanternier G, Lebbe C, Saiag P, Crickx B, Clerget-Darpoux F, Grandchamp B, Soufir N, Melan C: Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur J Hum Genet. 2005, 13 (8): 913-920. 10.1038/sj.ejhg.5201415.CrossRefPubMed
50.
Driver JA, Logroscino G, Buring JE, Gaziano JM, Kurth T: A prospective cohort study of cancer incidence following the diagnosis of Parkinson's disease. Cancer Epidemiol Biomarkers Prev. 2007, 16 (6): 1260-1265. 10.1158/1055-9965.EPI-07-0038.CrossRefPubMed
51.
Olsen JH, Friis S, Frederiksen K: Malignant melanoma and other types of cancer preceding Parkinson disease. Epidemiology. 2006, 17 (5): 582-587. 10.1097/01.ede.0000229445.90471.5e.CrossRefPubMed
52.
Olsen JH, Friis S, Frederiksen K, McLaughlin JK, Mellemkjaer L, Moller H: Atypical cancer pattern in patients with Parkinson's disease. Br J Cancer. 2005, 92 (1): 201-205. 10.1038/sj.bjc.6602279.CrossRefPubMed
53.
Herrero Hernandez E: Pigmentation genes link Parkinson's disease to melanoma, opening a window on both etiologies. Med Hypotheses. 2009, 72 (3): 280-284. 10.1016/j.mehy.2008.10.011.CrossRefPubMed
54.
Sturm RA, Teasdale RD, Box NF: Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene. 2001, 277 (1-2): 49-62. 10.1016/S0378-1119(01)00694-1.CrossRefPubMed
55.
Fedorow H, Tribl F, Halliday G, Gerlach M, Riederer P, Double KL: Neuromelanin in human dopamine neurons: comparison with peripheral melanins and relevance to Parkinson's disease. Prog Neurobiol. 2005, 75 (2): 109-124. 10.1016/j.pneurobio.2005.02.001.CrossRefPubMed
56.
Smith AP, Hoek K, Becker D: Whole-genome expression profiling of the melanoma progression pathway reveals marked molecular differences between nevi/melanoma in situ and advanced-stage melanomas. Cancer Biol Ther. 2005, 4 (9): 1018-1029.CrossRefPubMed
57.
Marciniak SJ, Ron D: Endoplasmic reticulum stress signaling in disease. Physiol Rev. 2006, 86 (4): 1133-1149. 10.1152/physrev.00015.2006.CrossRefPubMed
58.
Lindholm D, Wootz H, Korhonen L: ER stress and neurodegenerative diseases. Cell Death Differ. 2006, 13 (3): 385-392. 10.1038/sj.cdd.4401778.CrossRefPubMed
59.
Rao RV, Bredesen DE: Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr Opin Cell Biol. 2004, 16 (6): 653-662. 10.1016/j.ceb.2004.09.012.CrossRefPubMedPubMedCentral
60.
Ryu EJ, Harding HP, Angelastro JM, Vitolo OV, Ron D, Greene LA: Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson's disease. J Neurosci. 2002, 22 (24): 10690-10698.PubMed
61.
Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, Cao S, Caldwell KA, Caldwell GA, Marsischky G, Kolodner RD, Labaer J, Rochet JC, Bonini NM, Lindquist S: Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science. 2006, 313 (5785): 324-328. 10.1126/science.1129462.CrossRefPubMedPubMedCentral
62.
Hoozemans JJ, van Haastert ES, Eikelenboom P, de Vos RA, Rozemuller JM, Scheper W: Activation of the unfolded protein response in Parkinson's disease. Biochem Biophys Res Commun. 2007, 354 (3): 707-711. 10.1016/j.bbrc.2007.01.043.CrossRefPubMed
63.
64.
DeStefano AL, Lew MF, Golbe LI, Mark MH, Lazzarini AM, Guttman M, Montgomery E, Waters CH, Singer C, Watts RL, Currie LJ, Wooten GF, Maher NE, Wilk JB, Sullivan KM, Slater KM, Saint-Hilaire MH, Feldman RG, Suchowersky O, Lafontaine AL, Labelle N, Growdon JH, Vieregge P, Pramstaller PP, Klein C, Hubble JP, Reider CR, Stacy M, MacDonald ME, Gusella JF, Myers RH: PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study. American journal of human genetics. 2002, 70 (5): 1089-1095. 10.1086/339814.CrossRefPubMedPubMedCentral
65.
Pankratz N, Uniacke SK, Halter CA, Rudolph A, Shults CW, Conneally PM, Foroud T, Nichols WC: Genes influencing Parkinson disease onset: replication of PARK3 and identification of novel loci. Neurology. 2004, 62 (9): 1616-1618.CrossRefPubMed
66.
Zhang Y, James M, Middleton FA, Davis RL: Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms. Am J Med Genet B Neuropsychiatr Genet. 2005, 137B (1): 5-16. 10.1002/ajmg.b.30195.CrossRefPubMed
67.
Henderson DM, Conner SD: A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. Mol Biol Cell. 2007, 18 (7): 2698-2706. 10.1091/mbc.E06-09-0831.CrossRefPubMedPubMedCentral
68.
Kametaka S, Moriyama K, Burgos PV, Eisenberg E, Greene LE, Mattera R, Bonifacino JS: Canonical interaction of cyclin G associated kinase with adaptor protein 1 regulates lysosomal enzyme sorting. Mol Biol Cell. 2007, 18 (8): 2991-3001. 10.1091/mbc.E06-12-1162.CrossRefPubMedPubMedCentral
69.
Sevlever D, Jiang P, Yen SH: Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species. Biochemistry. 2008, 47 (36): 9678-9687. 10.1021/bi800699v.CrossRefPubMedPubMedCentral
70.
Li YJ, Scott WK, Hedges DJ, Zhang F, Gaskell PC, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Allen FA, Goetz CG, Mastaglia F, Stajich JM, Gibson RA, Middleton LT, Saunders AM, Scott BL, Small GW, Nicodemus KK, Reed AD, Schmechel DE, Welsh-Bohmer KA, Conneally PM, Roses AD, Gilbert JR, Vance JM, Haines JL, Pericak-Vance MA: Age at onset in two common neurodegenerative diseases is genetically controlled. American journal of human genetics. 2002, 70 (4): 985-993. 10.1086/339815.CrossRefPubMedPubMedCentral
71.
Bouchard L, Bouchard C, Chagnon YC, Perusse L: Evidence of linkage and association with body fatness and abdominal fat on chromosome 15q26. Obesity (Silver Spring). 2007, 15 (8): 2061-2070. 10.1038/oby.2007.245.CrossRef
72.
Verma R, Holmans P, Knowles JA, Grover D, Evgrafov OV, Crowe RR, Scheftner WA, Weissman MM, DePaulo JR, Potash JB, Levinson DF: Linkage disequilibrium mapping of a chromosome 15q25-26 major depression linkage region and sequencing of NTRK3. Biol Psychiatry. 2008, 63 (12): 1185-1189. 10.1016/j.biopsych.2008.02.005.CrossRefPubMedPubMedCentral
73.
Djousse L, Knowlton B, Hayden MR, Almqvist EW, Brinkman RR, Ross CA, Margolis RL, Rosenblatt A, Durr A, Dode C, Morrison PJ, Novelletto A, Frontali M, Trent RJ, McCusker E, Gomez-Tortosa E, Mayo Cabrero D, Jones R, Zanko A, Nance M, Abramson RK, Suchowersky O, Paulsen JS, Harrison MB, Yang Q, Cupples LA, Mysore J, Gusella JF, MacDonald ME, Myers RH: Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16. Neurogenetics. 2004, 5 (2): 109-114. 10.1007/s10048-004-0175-2.CrossRefPubMedPubMedCentral
74.
Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, Marder K, Penchaszadeh G, Roberts SA, Gayan J, Brocklebank D, Cherny SS, Cardon LR, Gray J, Dlouhy SR, Wiktorski S, Hodes ME, Conneally PM, Penney JB, Gusella J, Cha JH, Irizarry M, Rosas D, Hersch S, Hollingsworth Z, MacDonald M, Young AB, Andresen JM, Housman DE, De Young MM, Bonilla E, Stillings T, Negrette A, Snodgrass SR, Martinez-Jaurrieta MD, Ramos-Arroyo MA, Bickham J, Ramos JS, Marshall F, Shoulson I, Rey GJ, Feigin A, Arnheim N, Acevedo-Cruz A, Acosta L, Alvir J, Fischbeck K, Thompson LM, Young A, Dure L, O'Brien CJ, Paulsen J, Brickman A, Krch D, Peery S, Hogarth P, Higgins DS, Landwehrmeyer B: Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proceedings of the National Academy of Sciences of the United States of America. 2004, 101 (10): 3498-3503. 10.1073/pnas.0308679101.CrossRefPubMedPubMedCentral
75.
Andresen JM, Gayan J, Cherny SS, Brocklebank D, Alkorta-Aranburu G, Addis EA, Cardon LR, Housman DE, Wexler NS: Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds. J Med Genet. 2007, 44 (1): 44-50. 10.1136/jmg.2006.045153.CrossRefPubMed
Metadata
Title
Genomewide association study for onset age in Parkinson disease
Authors
Jeanne C Latourelle
Nathan Pankratz
Alexandra Dumitriu
Jemma B Wilk
Stefano Goldwurm
Gianni Pezzoli
Claudio B Mariani
Anita L DeStefano
Cheryl Halter
James F Gusella
William C Nichols
Richard H Myers
Tatiana Foroud
the PSG -PROGENI and GenePD Investigators, Coordinators and Molecular Genetic Laboratories
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2009
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-10-98

Other articles of this Issue 1/2009

BMC Medical Genetics 1/2009 Go to the issue

Research article

Identification of a pleiotropic locus on chromosome 7q for a composite left ventricular wall thickness factor and body mass index: the HyperGEN Study

Research article

Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI

Research article

The INSIG2 rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohorts

Research article

Genetic effect of CysLTR2 polymorphisms on its mRNA synthesis and stabilization

Research article

A new CYP21A1P/CYP21A2chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form

Technical advance

Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing®technology