Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression

Neurobiology of Aging

Volumn 37, Issue , 2016, Pages 209.e1-209.e7

  Davis, Albert A ^a   Andruska, Kristin M ^a   Benitez, Bruno A ^a   Racette, Brad A ^a,b   Perlmutter, Joel S ^a,c   Cruchaga, Carlos ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^c WASHINGTON UNIVERSITY   (United States)

Author keywords

Age at onset; GBA; MAPT; Motor progression; Parkinson disease; SNCA

Indexed keywords

ACMSD GENE; ADULT; ARTICLE; CONTROLLED STUDY; FEMALE; GAK GENE; GBA GENE; GENE; GENE LOCUS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HAPLOTYPE; HUMAN; LAMP3 GENE; MAJOR CLINICAL STUDY; MALE; MAPT GENE; MCCC1 GENE; ONSET AGE; PARKINSON DISEASE; RISK ASSESSMENT; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; SNCA GENE; STK39 GENE; TMEM163 GENE; TMEM175 GENE; AGED; CASE CONTROL STUDY; DISEASE COURSE; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GENOTYPING TECHNIQUE; INFORMATION PROCESSING; MIDDLE AGED; MOTOR ACTIVITY; PHENOTYPE; RISK; VERY ELDERLY;

ALPHA SYNUCLEIN; BETA GLUCOSIDASE; MAPT PROTEIN, HUMAN; SNCA PROTEIN, HUMAN; TAU PROTEIN;

AGE OF ONSET; AGED; AGED, 80 AND OVER; ALPHA-SYNUCLEIN; BETA-GLUCOSIDASE; CASE-CONTROL STUDIES; DATASETS AS TOPIC; DISEASE PROGRESSION; FEMALE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPING TECHNIQUES; HAPLOTYPES; HUMANS; MALE; MIDDLE AGED; MOTOR ACTIVITY; PARKINSON DISEASE; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK; TAU PROTEINS;

EID: 84951075844     PISSN: 01974580     EISSN: 15581497     Source Type: Journal    
DOI: 10.1016/j.neurobiolaging.2015.09.014     Document Type: Article

References (49)

1. Abbas, N., Lucking, C.B., Ricard, S., Durr, A., Bonifati, V., De Michele, G., Bouley, S., Vaughan, J.R., Gasser, T., Marconi, R., Broussolle, E., Brefel-Courbon, C., Harhangi, B.S., Oostra, B.A., Fabrizio, E., Bohme, G.A., Pradier, L., Wood, N.W., Filla, A., Meco, G., Denefle, P., Agid, Y., Brice, A., A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease. Hum. Mol. Genet. 8 (1999), 567–574.
2. Abuirmeileh, A., Harkavyi, A., Kingsbury, A., Lever, R., Whitton, P.S., The CRF-like peptide urocortin produces a long-lasting recovery in rats made hemiparkinsonian by 6-hydroxydopamine or lipopolysaccharide. J. Neurol. Sci. 271 (2008), 131–136.
3. Aharon-Peretz, J., Rosenbaum, H., Gershoni-Baruch, R., Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N. Engl. J. Med. 351 (2004), 1972–1977.
4. Bonifati, V., Rizzu, P., van Baren, M.J., Schaap, O., Breedveld, G.J., Krieger, E., Dekker, M.C., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J.W., Vanacore, N., van Swieten, J.C., Brice, A., Meco, G., van Duijn, C.M., Oostra, B.A., Heutink, P., Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299 (2003), 256–259.
5. Bonifati, V., Rohe, C.F., Breedveld, G.J., Fabrizio, E., De Mari, M., Tassorelli, C., Tavella, A., Marconi, R., Nicholl, D.J., Chien, H.F., Fincati, E., Abbruzzese, G., Marini, P., De Gaetano, A., Horstink, M.W., Maat-Kievit, J.A., Sampaio, C., Antonini, A., Stocchi, F., Montagna, P., Toni, V., Guidi, M., Dalla Libera, A., Tinazzi, M., De Pandis, F., Fabbrini, G., Goldwurm, S., de Klein, A., Barbosa, E., Lopiano, L., Martignoni, E., Lamberti, P., Vanacore, N., Meco, G., Oostra, B.A., Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes. Neurology 65 (2005), 87–95.
6. Brockmann, K., Srulijes, K., Hauser, A.K., Schulte, C., Csoti, I., Gasser, T., Berg, D., GBA-associated PD presents with nonmotor characteristics. Neurology 77 (2011), 276–280.
7. Brockmann, K., Srulijes, K., Pflederer, S., Hauser, A.K., Schulte, C., Maetzler, W., Gasser, T., Berg, D., GBA-associated Parkinson's disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov. Disord. 30 (2015), 407–411.
8. Burre, J., Sharma, M., Sudhof, T.C., Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329 (2010), 1663–1667.
9. Burre, J., Sharma, M., Tsetsenis, T., Buchman, V., Etherton, M.R., Sudhof, T.C., α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), E4274–E4283.
10. Cardo, L.F., Coto, E., de Mena, L., Ribacoba, R., Lorenzo-Betancor, O., Pastor, P., Samaranch, L., Mata, I.F., Diaz, M., Moris, G., Menendez, M., Corao, A.I., Alvarez, V., A search for SNCA 3' UTR variants identified SNP rs356165 as a determinant of disease risk and onset age in Parkinson's disease. J. Mol. Neurosci. 47 (2012), 425–430.
11. Charlesworth, G., Gandhi, S., Bras, J.M., Barker, R.A., Burn, D.J., Chinnery, P.F., Gentleman, S.M., Guerreiro, R., Hardy, J., Holton, J.L., Lees, A., Morrison, K., Sheerin, U.M., Williams, N., Morris, H., Revesz, T., Wood, N.W., Tau acts as an independent genetic risk factor in pathologically proven PD. Neurobiol. Aging 33 (2012), 838.e7–838.e11.
12. Clark, L.N., Ross, B.M., Wang, Y., Mejia-Santana, H., Harris, J., Louis, E.D., Cote, L.J., Andrews, H., Fahn, S., Waters, C., Ford, B., Frucht, S., Ottman, R., Marder, K., Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease. Neurology 69 (2007), 1270–1277.
13. Cruchaga, C., Haller, G., Chakraverty, S., Mayo, K., Vallania, F.L., Mitra, R.D., Faber, K., Williamson, J., Bird, T., Diaz-Arrastia, R., Foroud, T.M., Boeve, B.F., Graff-Radford, N.R., St Jean, P., Lawson, M., Ehm, M.G., Mayeux, R., Goate, A.M., Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS One, 7, 2012, e31039.
14. Das, G., Misra, A.K., Das, S.K., Ray, K., Ray, J., Microtubule-associated protein tau (MAPT) influences the risk of Parkinson's disease among Indians. Neurosci. Lett. 460 (2009), 16–20.
15. Desikan, R.S., Schork, A.J., Wang, Y., Witoelar, A., Sharma, M., McEvoy, L.K., Holland, D., Brewer, J.B., Chen, C.H., Thompson, W.K., Harold, D., Williams, J., Owen, M.J., O'Donovan, M.C., Pericak-Vance, M.A., Mayeux, R., Haines, J.L., Farrer, L.A., Schellenberg, G.D., Heutink, P., Singleton, A.B., Brice, A., Wood, N.W., Hardy, J., Martinez, M., Choi, S.H., DeStefano, A., Ikram, M.A., Bis, J.C., Smith, A., Fitzpatrick, A.L., Launer, L., van Duijn, C., Seshadri, S., Ulstein, I.D., Aarsland, D., Fladby, T., Djurovic, S., Hyman, B.T., Snaedal, J., Stefansson, H., Stefansson, K., Gasser, T., Andreassen, O.A., Dale, A.M., Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. Mol. Psychiatry, 2015, 10.1038/mp.2015.6.
16. Elbaz, A., Ross, O.A., Ioannidis, J.P., Soto-Ortolaza, A.I., Moisan, F., Aasly, J., Annesi, G., Bozi, M., Brighina, L., Chartier-Harlin, M.C., Destee, A., Ferrarese, C., Ferraris, A., Gibson, J.M., Gispert, S., Hadjigeorgiou, G.M., Jasinska-Myga, B., Klein, C., Kruger, R., Lambert, J.C., Lohmann, K., van de Loo, S., Loriot, M.A., Lynch, T., Mellick, G.D., Mutez, E., Nilsson, C., Opala, G., Puschmann, A., Quattrone, A., Sharma, M., Silburn, P.A., Stefanis, L., Uitti, R.J., Valente, E.M., Vilarino-Guell, C., Wirdefeldt, K., Wszolek, Z.K., Xiromerisiou, G., Maraganore, D.M., Farrer, M.J., Independent and joint effects of the MAPT and SNCA genes in Parkinson disease. Ann. Neurol. 69 (2011), 778–792.
17. Escott-Price, V., Nalls, M.A., Morris, H.R., Lubbe, S., Brice, A., Gasser, T., Heutink, P., Wood, N.W., Hardy, J., Singleton, A.B., Williams, N.M., Polygenic risk of Parkinson disease is correlated with disease age at onset. Ann. Neurol. 77 (2015), 582–591.
18. Gan-Or, Z., Bar-Shira, A., Mirelman, A., Gurevich, T., Giladi, N., Orr-Urtreger, A., The age at motor symptoms onset in LRRK2-associated Parkinson's disease is affected by a variation in the MAPT locus: a possible interaction. J. Mol. Neurosci. 46 (2012), 541–544.
19. Golub, Y., Berg, D., Calne, D.B., Pfeiffer, R.F., Uitti, R.J., Stoessl, A.J., Wszolek, Z.K., Farrer, M.J., Mueller, J.C., Gasser, T., Fuchs, J., Genetic factors influencing age at onset in LRRK2-linked Parkinson disease. Parkinsonism Relat. Disord. 15 (2009), 539–541.
20. Harms, M.B., Neumann, D., Benitez, B.A., Cooper, B., Carrell, D., Racette, B.A., Perlmutter, J.S., Goate, A., Cruchaga, C., Parkinson disease is not associated with C9ORF72 repeat expansions. Neurobiol. Aging 34 (2013), 1519.e1–1519.e2.
21. Hughes, A.J., Daniel, S.E., Kilford, L., Lees, A.J., Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry 55 (1992), 181–184.
22. International Parkinson's Disease Genomics Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2). A two-stage meta-analysis identifies several new loci for Parkinson's disease. PLoS Genet., 7, 2011, e1002142.
23. Keller, M.F., Saad, M., Bras, J., Bettella, F., Nicolaou, N., Simon-Sanchez, J., Mittag, F., Buchel, F., Sharma, M., Gibbs, J.R., Schulte, C., Moskvina, V., Durr, A., Holmans, P., Kilarski, L.L., Guerreiro, R., Hernandez, D.G., Brice, A., Ylikotila, P., Stefansson, H., Majamaa, K., Morris, H.R., Williams, N., Gasser, T., Heutink, P., Wood, N.W., Hardy, J., Martinez, M., Singleton, A.B., Nalls, M.A., Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease. Hum. Mol. Genet. 21 (2012), 4996–5009.
24. Klebe, S., Golmard, J.L., Nalls, M.A., Saad, M., Singleton, A.B., Bras, J.M., Hardy, J., Simon-Sanchez, J., Heutink, P., Kuhlenbaumer, G., Charfi, R., Klein, C., Hagenah, J., Gasser, T., Wurster, I., Lesage, S., Lorenz, D., Deuschl, G., Durif, F., Pollak, P., Damier, P., Tison, F., Durr, A., Amouyel, P., Lambert, J.C., Tzourio, C., Maubaret, C., Charbonnier-Beaupel, F., Tahiri, K., Vidailhet, M., Martinez, M., Brice, A., Corvol, J.C., The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism. J. Neurol. Neurosurg. Psychiatry 84 (2013), 666–673.
25. Kobayashi, H., Ujike, H., Hasegawa, J., Yamamoto, M., Kanzaki, A., Sora, I., Correlation of tau gene polymorphism with age at onset of Parkinson's disease. Neurosci. Lett. 405 (2006), 202–206.
26. Latourelle, J.C., Pankratz, N., Dumitriu, A., Wilk, J.B., Goldwurm, S., Pezzoli, G., Mariani, C.B., DeStefano, A.L., Halter, C., Gusella, J.F., Nichols, W.C., Myers, R.H., Foroud, T., Genomewide association study for onset age in Parkinson disease. BMC Med. Genet., 10, 2009, 98.
27. Liu, X., Cheng, R., Verbitsky, M., Kisselev, S., Browne, A., Mejia-Sanatana, H., Louis, E.D., Cote, L.J., Andrews, H., Waters, C., Ford, B., Frucht, S., Fahn, S., Marder, K., Clark, L.N., Lee, J.H., Genome-wide association study identifies candidate genes for Parkinson's disease in an Ashkenazi Jewish population. BMC Med. Genet., 12, 2011, 104.
28. Maraganore, D.M., de Andrade, M., Lesnick, T.G., Strain, K.J., Farrer, M.J., Rocca, W.A., Pant, P.V., Frazer, K.A., Cox, D.R., Ballinger, D.G., High-resolution whole-genome association study of Parkinson disease. Am. J. Hum. Genet. 77 (2005), 685–693.
29. Moskvina, V., Harold, D., Russo, G., Vedernikov, A., Sharma, M., Saad, M., Holmans, P., Bras, J.M., Bettella, F., Keller, M.F., Nicolaou, N., Simon-Sanchez, J., Gibbs, J.R., Schulte, C., Durr, A., Guerreiro, R., Hernandez, D., Brice, A., Stefansson, H., Majamaa, K., Gasser, T., Heutink, P., Wood, N., Martinez, M., Singleton, A.B., Nalls, M.A., Hardy, J., Owen, M.J., O'Donovan, M.C., Williams, J., Morris, H.R., Williams, N.M., Analysis of genome-wide association studies of Alzheimer disease and of Parkinson disease to determine if these 2 diseases share a common genetic risk. JAMA Neurol. 70 (2013), 1268–1276.
30. Myers, A.J., Kaleem, M., Marlowe, L., Pittman, A.M., Lees, A.J., Fung, H.C., Duckworth, J., Leung, D., Gibson, A., Morris, C.M., de Silva, R., Hardy, J., The H1c haplotype at the MAPT locus is associated with Alzheimer's disease. Hum. Mol. Genet. 14 (2005), 2399–2404.
31. Nalls, M.A., Pankratz, N., Lill, C.M., Do, C.B., Hernandez, D.G., Saad, M., DeStefano, A.L., Kara, E., Bras, J., Sharma, M., Schulte, C., Keller, M.F., Arepalli, S., Letson, C., Edsall, C., Stefansson, H., Liu, X., Pliner, H., Lee, J.H., Cheng, R., Ikram, M.A., Ioannidis, J.P., Hadjigeorgiou, G.M., Bis, J.C., Martinez, M., Perlmutter, J.S., Goate, A., Marder, K., Fiske, B., Sutherland, M., Xiromerisiou, G., Myers, R.H., Clark, L.N., Stefansson, K., Hardy, J.A., Heutink, P., Chen, H., Wood, N.W., Houlden, H., Payami, H., Brice, A., Scott, W.K., Gasser, T., Bertram, L., Eriksson, N., Foroud, T., Singleton, A.B., Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 377 (2011), 641–649.
32. Nalls, M.A., Plagnol, V., Hernandez, D.G., Sharma, M., Sheerin, U.M., Saad, M., Simon-Sanchez, J., Schulte, C., Lesage, S., Sveinbjornsdottir, S., Stefansson, K., Martinez, M., Hardy, J., Heutink, P., Brice, A., Gasser, T., Singleton, A.B., Wood, N.W., Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat. Genet. 46 (2014), 989–993.
33. Nishioka, K., Vilarino-Guell, C., Cobb, S.A., Kachergus, J.M., Ross, O.A., Wider, C., Gibson, R.A., Hentati, F., Farrer, M.J., Glucocerebrosidase mutations are not a common risk factor for Parkinson disease in North Africa. Neurosci. Lett. 477 (2010), 57–60.
34. Paisan-Ruiz, C., Jain, S., Evans, E.W., Gilks, W.P., Simon, J., van der Brug, M., Lopez de Munain, A., Aparicio, S., Gil, A.M., Khan, N., Johnson, J., Martinez, J.R., Nicholl, D., Carrera, I.M., Pena, A.S., de Silva, R., Lees, A., Marti-Masso, J.F., Perez-Tur, J., Wood, N.W., Singleton, A.B., Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44 (2004), 595–600.
35. Pankratz, N., Wilk, J.B., Latourelle, J.C., DeStefano, A.L., Halter, C., Pugh, E.W., Doheny, K.F., Gusella, J.F., Nichols, W.C., Foroud, T., Myers, R.H., Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Hum. Genet. 124 (2009), 593–605.
36. Pittman, A.M., Myers, A.J., Abou-Sleiman, P., Fung, H.C., Kaleem, M., Marlowe, L., Duckworth, J., Leung, D., Williams, D., Kilford, L., Thomas, N., Morris, C.M., Dickson, D., Wood, N.W., Hardy, J., Lees, A.J., de Silva, R., Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration. J. Med. Genet. 42 (2005), 837–846.
37. Polymeropoulos, M.H., Lavedan, C., Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E.S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R.C., Di Iorio, G., Golbe, L.I., Nussbaum, R.L., Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276 (1997), 2045–2047.
38. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J., Sham, P.C., PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81 (2007), 559–575.
39. Racette, B.A., Rundle, M., Parsian, A., Perlmutter, J.S., Evaluation of a screening questionnaire for genetic studies of Parkinson's disease. Am. J. Med. Genet. 88 (1999), 539–543.
40. Rademakers, R., Melquist, S., Cruts, M., Theuns, J., Del-Favero, J., Poorkaj, P., Baker, M., Sleegers, K., Crook, R., De Pooter, T., Bel Kacem, S., Adamson, J., Van den Bossche, D., Van den Broeck, M., Gass, J., Corsmit, E., De Rijk, P., Thomas, N., Engelborghs, S., Heckman, M., Litvan, I., Crook, J., De Deyn, P.P., Dickson, D., Schellenberg, G.D., VanBroeckhoven, C., Hutton, M.L., High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy. Hum. Mol. Genet. 14 (2005), 3281–3292.
41. Ramaker, C., Marinus, J., Stiggelbout, A.M., Van Hilten, B.J., Systematic evaluation of rating scales for impairment and disability in Parkinson's disease. Mov. Disord. 17 (2002), 867–876.
42. Ritz, B., Rhodes, S.L., Bordelon, Y., Bronstein, J., α-Synuclein genetic variants predict faster motor symptom progression in idiopathic Parkinson disease. PLoS One, 7, 2012, e36199.
43. Satake, W., Nakabayashi, Y., Mizuta, I., Hirota, Y., Ito, C., Kubo, M., Kawaguchi, T., Tsunoda, T., Watanabe, M., Takeda, A., Tomiyama, H., Nakashima, K., Hasegawa, K., Obata, F., Yoshikawa, T., Kawakami, H., Sakoda, S., Yamamoto, M., Hattori, N., Murata, M., Nakamura, Y., Toda, T., Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat. Genet. 41 (2009), 1303–1307.
44. Siderowf, A., McDermott, M., Kieburtz, K., Blindauer, K., Plumb, S., Shoulson, I., Test-retest reliability of the unified Parkinson's disease rating scale in patients with early Parkinson's disease: results from a multicenter clinical trial. Mov. Disord. 17 (2002), 758–763.
45. 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., Klein, C., Goate, A., Perlmutter, J., Bonin, M., Nalls, M.A., Illig, T., Gieger, C., Houlden, H., Steffens, M., Okun, M.S., Racette, B.A., Cookson, M.R., Foote, K.D., Fernandez, H.H., Traynor, B.J., Schreiber, S., Arepalli, S., Zonozi, R., Gwinn, K., van der Brug, M., Lopez, G., Chanock, S.J., Schatzkin, A., Park, Y., Hollenbeck, A., Gao, J., Huang, X., Wood, N.W., Lorenz, D., Deuschl, G., Chen, H., Riess, O., Hardy, J.A., Singleton, A.B., Gasser, T., Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet. 41 (2009), 1308–1312.
46. Wang, J., Liu, Z.L., Chen, B., Association study of dopamine D2, D3 receptor gene polymorphisms with motor fluctuations in PD. Neurology 56 (2001), 1757–1759.
47. Whitehouse, P.J., Vale, W.W., Zweig, R.M., Singer, H.S., Mayeux, R., Kuhar, M.J., Price, D.L., De Souza, E.B., Reductions in corticotropin releasing factor-like immunoreactivity in cerebral cortex in Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy. Neurology 37 (1987), 905–909.
48. Winder-Rhodes, S.E., Evans, J.R., Ban, M., Mason, S.L., Williams-Gray, C.H., Foltynie, T., Duran, R., Mencacci, N.E., Sawcer, S.J., Barker, R.A., Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort. Brain 136 (2013), 392–399.
49. Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., Kachergus, J., Hulihan, M., Uitti, R.J., Calne, D.B., Stoessl, A.J., Pfeiffer, R.F., Patenge, N., Carbajal, I.C., Vieregge, P., Asmus, F., Muller-Myhsok, B., Dickson, D.W., Meitinger, T., Strom, T.M., Wszolek, Z.K., Gasser, T., Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44 (2004), 601–607.