nach oben

Erschienen in:

01.02.2020 | Original Paper

Overlapping genetic architecture between Parkinson disease and melanoma

verfasst von: Umber Dube, Laura Ibanez, John P. Budde, Bruno A. Benitez, Albert A. Davis, Oscar Harari, Mark M. Iles, Matthew H. Law, Kevin M. Brown, Carlos Cruchaga, 23andMe Research Team, Melanoma-Meta-analysis Consortium

Erschienen in: Acta Neuropathologica | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case–control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10–0.24; P = 4.09 × 10⁻⁰⁶) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 × 10⁻⁰⁴) and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.

Nur mit Berechtigung zugänglich

Ascherio A, Schwarzschild MA (2016) The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol 15:1257–1272. https://doi.org/10.1016/S1474-4422(16)30230-7 CrossRefPubMed

Baizabal-Carvallo JF, Jankovic J (2016) Parkinsonism, movement disorders and genetics in frontotemporal dementia. Nature Rev Neurol 12:175–185. https://doi.org/10.1038/nrneurol.2016.14 CrossRef

Beecham GW, Dickson DW, Scott WK, Martin ER, Schellenberg G, Nuytemans K et al (2015) PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease. Neurology 84:972–980. https://doi.org/10.1212/WNL.0000000000001332 CrossRefPubMedPubMedCentral

Bernstein JE, Medenica M, Soltani K, Solomon A, Lorincz AL (1980) Levodopa administration and multiple primary cutaneous melanomas. Arch Dermatol 116:1041–1044. https://doi.org/10.1001/archderm.1980.01640330079019 CrossRefPubMed

Bertoni JM, Arlette JP, Fernandez HH, Fitzer-Attas C, Frei K, Hassan MN et al (2010) Increased melanoma risk in parkinson disease: a prospective clinicopathological study. Arch Neurol 67:347–352. https://doi.org/10.1001/archneurol.2010.1 CrossRefPubMed

Bliss JM, Ford D, Swerdlow AJ, Armstrong BK, Cristofolini M, Elwood JM et al (1995) Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. The International Melanoma Analysis Group (IMAGE). Int J Cancer 62:367–376CrossRefPubMed

Boeve BF, Hutton M (2008) Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Arch Neurol 65:460–464. https://doi.org/10.1001/archneur.65.4.460 CrossRefPubMedPubMedCentral

Boyle EA, Li YI, Pritchard JK (2017) An expanded view of complex traits: from polygenic to omnigenic. Cell 169:1177–1186. https://doi.org/10.1016/j.cell.2017.05.038 CrossRefPubMedPubMedCentral

Braak H, Del Tredici K (2017) Neuropathological staging of brain pathology in sporadic Parkinson’s disease: separating the wheat from the chaff. J Parkinson’s Dis 7:S71–S85. https://doi.org/10.3233/JPD-179001 CrossRef

10.

Braak H, Rüb U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110:517–536. https://doi.org/10.1007/s00702-002-0808-2 CrossRefPubMed

11.

Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Schizophrenia Working Group of the Psychiatric Genomics Consortium et al (2015) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet 47:291–295. https://doi.org/10.1038/ng.3211 CrossRefPubMedPubMedCentral

12.

Cai N, Revez JA, Adams MJ, Andlauer TFM, Breen G, Byrne EM et al (2019) Minimal phenotyping yields GWAS hits of low specificity for major depression. bioRxiv 2019:440735. https://doi.org/10.1101/440735

13.

Chang D, Nalls MA, Hallgrímsdóttir IB, Hunkapiller J, van der Brug M, Cai F et al (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet. https://doi.org/10.1038/ng.3955 CrossRefPubMedPubMedCentral

14.

Chen H, Ritz B (2019) The search for environmental causes of parkinson’s disease: moving forward. J Parkinsons Dis 8:S9–S17. https://doi.org/10.3233/jpd-181493 CrossRefPubMedPubMedCentral

15.

Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330:55–60. https://doi.org/10.1126/science.1193270 CrossRefPubMedPubMedCentral

16.

Craig S, Earnshaw CH, Virós A (2018) Ultraviolet light and melanoma. J Pathol 244:578–585. https://doi.org/10.1002/path.5039 CrossRefPubMed

17.

Dalvin LA, Damento GM, Yawn BP, Abbott BA, Hodge DO, Pulido JS (2017) Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc 92:1070–1079. https://doi.org/10.1016/j.mayocp.2017.03.014 CrossRefPubMed

18.

De Pablo-Fernández E, Lees AJ, Holton JL, Warner TT (2019) Prognosis and neuropathologic correlation of clinical subtypes of Parkinson disease. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2018.4377 CrossRefPubMedPubMedCentral

19.

Dong J, Gao J, Nalls M, Gao X, Huang X, Han J et al (2014) Susceptibility loci for pigmentation and melanoma in relation to Parkinson’s disease. Neurobiol Aging 35:1512.e5–1512.e10. https://doi.org/10.1016/j.neurobiolaging.2013.12.020 CrossRef

20.

Dong X, Liao Z, Gritsch D, Hadzhiev Y, Bai Y, Locascio JJ et al (2018) Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nat Neurosci 21:1482. https://doi.org/10.1038/s41593-018-0223-0 CrossRefPubMedPubMedCentral

21.

Driver JA, Logroscino G, Buring JE, Gaziano JM, Kurth T (2007) A prospective cohort study of cancer incidence following the diagnosis of Parkinson’s disease. Cancer Epidemiol Biomarkers Prev 16:1260–1265. https://doi.org/10.1158/1055-9965.EPI-07-0038 CrossRefPubMed

22.

Duke DC, Moran LB, Pearce RKB, Graeber MB (2007) The medial and lateral substantia nigra in Parkinson’s disease: mRNA profiles associated with higher brain tissue vulnerability. Neurogenetics 8:83–94. https://doi.org/10.1007/s10048-006-0077-6 CrossRefPubMed

23.

Eisenhofer G, Tian H, Holmes C, Matsunaga J, Roffler-Tarlov S, Hearing VJ (2003) Tyrosinase: a developmentally specific major determinant of peripheral dopamine. FASEB J 17:1248–1255. https://doi.org/10.1096/fj.02-0736com CrossRefPubMed

24.

Elincx-Benizri S, Inzelberg R, Greenbaum L, Cohen OS, Yahalom G, Laitman Y et al (2014) The melanocortin 1 receptor (Mc1r) variants do not account for the co-occurrence of parkinson’s disease and malignant melanoma. J Mol Neurosci 54:820–825. https://doi.org/10.1007/s12031-014-0425-1 CrossRefPubMed

25.

Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ et al (2014) Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol 13:686–699. https://doi.org/10.1016/S1474-4422(14)70065-1 CrossRefPubMedPubMedCentral

26.

Foo JN, Zhao Y, Liu J, Tan E-K (2015) Nonsynonymous variants in MC1R are rare in Chinese Parkinson disease cases. Ann Neurol 78:152–153. https://doi.org/10.1002/ana.24419 CrossRefPubMed

27.

Freedman DM, Wu J, Chen H, Engels EA, Enewold LR, Freedman ND et al (2016) Associations between cancer and Parkinson’s disease in US elderly adults. Int J Epidemiol 45:741–751. https://doi.org/10.1093/ije/dyw016 CrossRefPubMedPubMedCentral

28.

Gan-Or Z, Mohsin N, Girard SL, Montplaisir JY, Ambalavanan A, Strong S et al (2016) The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder. Neurobiol Aging 43:180.e7–180.e13. https://doi.org/10.1016/j.neurobiolaging.2016.03.029 CrossRef

29.

Gao X, Simon KC, Han J, Schwarzschild MA, Ascherio A (2009) Family history of melanoma and Parkinson disease risk. Neurology 73:1286–1291. https://doi.org/10.1212/WNL.0b013e3181bd13a1 CrossRefPubMedPubMedCentral

30.

Gao X, Simon KC, Han J, Schwarzschild MA, Ascherio A (2009) Genetic determinants of hair color and parkinson’s disease risk. Ann Neurol 65:76–82. https://doi.org/10.1002/ana.21535 CrossRefPubMedPubMedCentral

31.

Gibbs RA, Belmont JW, Hardenbol P, Willis TD, Yu F, Yang H et al (2003) The international HapMap project. Nature 426:789–796. https://doi.org/10.1038/nature02168 CrossRef

32.

Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO (2000) Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133:338–347. https://doi.org/10.7326/0003-4819-133-5-200009050-00009 CrossRefPubMed

33.

Gross A, Racette BA, Camacho-Soto A, Dube U, Searles Nielsen S (2018) Use of medical care biases associations between Parkinson disease and other medical conditions. Neurology 90:e2155–e2165. https://doi.org/10.1212/WNL.0000000000005678 CrossRefPubMedPubMedCentral

34.

GTEx Consortium (2017) Genetic effects on gene expression across human tissues. Nature 550:204–213. https://doi.org/10.1038/nature24277 CrossRefPubMedCentral

35.

Gusev A, Ko A, Shi H, Bhatia G, Chung W, Penninx BWJH et al (2016) Integrative approaches for large-scale transcriptome-wide association studies. Nat Genet 48:245–252. https://doi.org/10.1038/ng.3506 CrossRefPubMedPubMedCentral

36.

Heilbron K, Noyce AJ, Fontanillas P, Alipanahi B, Nalls MA, Cannon P (2019) The Parkinson’s phenome—traits associated with Parkinson’s disease in a broadly phenotyped cohort. NPJ Parkinson’s Disease 5:4. https://doi.org/10.1038/s41531-019-0077-5

37.

Hu H-H, Kannengiesser C, Lesage S, André J, Mourah S, Michel L et al (2016) PARKIN inactivation links Parkinson’s disease to melanoma. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djv340 CrossRefPubMedPubMedCentral

38.

Hu Y, Li M, Lu Q, Weng H, Wang J, Zekavat SM et al (2019) A statistical framework for cross-tissue transcriptome-wide association analysis. Nat Genet 51:568. https://doi.org/10.1038/s41588-019-0345-7 CrossRefPubMedPubMedCentral

39.

Hung W-C, Yang JR, Yankaskas CL, Wong BS, Wu P-H, Pardo-Pastor C et al (2016) Confinement Sensing and signal optimization via Piezo1/PKA and myosin II pathways. Cell Rep 15:1430–1441. https://doi.org/10.1016/j.celrep.2016.04.035 CrossRefPubMedPubMedCentral

40.

Inzelberg R, Samuels Y, Azizi E, Qutob N, Inzelberg L, Domany E et al (2016) Parkinson disease (PARK) genes are somatically mutated in cutaneous melanoma. Neurol Genet 2:e70. https://doi.org/10.1212/NXG.0000000000000070 CrossRefPubMedPubMedCentral

41.

Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q et al (2019) Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv 2019:531210. https://doi.org/10.1101/531210

42.

Kareus SA, Figueroa KP, Cannon-Albright LA, Pulst SM (2012) Shared predispositions of parkinsonism and cancer: a population-based pedigree-linked study. Arch Neurol 69:1572–1577. https://doi.org/10.1001/archneurol.2012.2261 CrossRefPubMed

43.

Kim S, Kwon S-H, Kam T-I, Panicker N, Karuppagounder SS, Lee S et al (2019) Transneuronal propagation of pathologic α-Synuclein from the Gut to the brain models Parkinson’s Disease. Neuron. https://doi.org/10.1016/j.neuron.2019.05.035 CrossRefPubMedPubMedCentral

44.

Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC et al (2019) Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet 51:414–430. https://doi.org/10.1038/s41588-019-0358-2 CrossRefPubMedPubMedCentral

45.

Law MH, Bishop DT, Lee JE, Brossard M, Martin NG, Moses EK et al (2015) Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma. Nat Genet 47:987–995. https://doi.org/10.1038/ng.3373 CrossRefPubMedPubMedCentral

46.

Lee JM, Derkinderen P, Kordower JH, Freeman R, Munoz DG, Kremer T et al (2017) The search for a peripheral biopsy indicator of α-synuclein pathology for Parkinson disease. J Neuropathol Exp Neurol 76:2–15. https://doi.org/10.1093/jnen/nlw103 CrossRefPubMed

47.

Lesnick TG, Papapetropoulos S, Mash DC, Ffrench-Mullen J, Shehadeh L, de Andrade M et al (2007) A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS Genet 3:e98. https://doi.org/10.1371/journal.pgen.0030098 CrossRefPubMedPubMedCentral

48.

Levin L, Srour S, Gartner J, Kapitansky O, Qutob N, Dror S et al (2016) Parkin somatic mutations link melanoma and Parkinson’s disease. J Genet Genomics 43:369–379. https://doi.org/10.1016/j.jgg.2016.05.005 CrossRefPubMed

49.

Li Z, Del-Aguila JL, Dube U, Budde J, Martinez R, Black K et al (2018) Genetic variants associated with Alzheimer’s disease confer different cerebral cortex cell-type population structure. Genome Med 10:43. https://doi.org/10.1186/s13073-018-0551-4 CrossRefPubMedPubMedCentral

50.

Lill CM, Roehr JT, McQueen MB, Kavvoura FK, Bagade S, Schjeide B-MM et al (2012) Comprehensive research synopsis and systematic meta-analyses in Parkinson’s disease genetics: the PDGene database. PLoS Genet 8:e1002548. https://doi.org/10.1371/journal.pgen.1002548 CrossRefPubMedPubMedCentral

51.

Lisbôa-Nascimento T, Carriço JW, Calió ML, Bacchi AL, Carbonel AAF, Rigoni VL et al (2015) Identification of melanoma stem cells in long-term cultures and of SOX6 as a specific biomarker for these stem cells. J Cancer Epidemiol Treat 1(1):15–27. https://doi.org/10.24218/jcet.2015.07 CrossRef

52.

Liu CSC, Raychaudhuri D, Paul B, Chakrabarty Y, Ghosh AR, Rahaman O et al (2018) Cutting edge: piezo1 mechanosensors optimize human T cell activation. J Immunol 200:1255–1260. https://doi.org/10.4049/jimmunol.1701118 CrossRefPubMed

53.

Liu R, Gao X, Lu Y, Chen H (2011) Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology 76:2002–2009. https://doi.org/10.1212/WNL.0b013e31821e554e CrossRefPubMedPubMedCentral

54.

Lu Q, Li B, Ou D, Erlendsdottir M, Powles RL, Jiang T et al (2017) A powerful approach to estimating annotation-stratified genetic covariance via GWAS summary statistics. Am J Hum Genet 101:939–964. https://doi.org/10.1016/j.ajhg.2017.11.001 CrossRefPubMedPubMedCentral

55.

Lubbe SJ, Escott-Price V, Brice A, Gasser T, Hardy J, Heutink P et al (2016) Is the MC1R variant p. R160W associated with Parkinson’s? Ann Neurol 79:159–161. https://doi.org/10.1002/ana.24527 CrossRefPubMed

56.

Lubbe SJ, Escott-Price V, Brice A, Gasser T, Pittman AM, Bras J et al (2016) Rare variants analysis of cutaneous malignant melanoma genes in Parkinson’s disease. Neurobiol Aging 48:222.e1–222.e7. https://doi.org/10.1016/j.neurobiolaging.2016.07.013 CrossRef

57.

Mancuso N, Shi H, Goddard P, Kichaev G, Gusev A, Pasaniuc B (2017) Integrating gene expression with summary association statistics to identify genes associated with 30 complex traits. Am J Hum Genet 100:473–487. https://doi.org/10.1016/j.ajhg.2017.01.031 CrossRefPubMedPubMedCentral

58.

Mazzuoli-Weber G, Kugler EM, Bühler CI, Kreutz F, Demir IE, Ceyhan OG et al (2019) Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity? Cell Tissue Res 375:605–618. https://doi.org/10.1007/s00441-018-2926-7 CrossRefPubMed

59.

Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J et al (2018) Transcription and signaling regulators in developing neuronal subtypes of mouse and human enteric nervous system. Gastroenterology 154:624–636. https://doi.org/10.1053/j.gastro.2017.10.005 CrossRefPubMed

60.

Milev MP, Graziano C, Karall D, Kuper WFE, Al-Deri N, Cordelli DM et al (2018) Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts. J Med Genet 55:753–764. https://doi.org/10.1136/jmedgenet-2018-105441 CrossRefPubMed

61.

Montpetit B, Conibear E (2009) Identification of the novel TRAPP associated protein Tca17. Traffic 10:713–723. https://doi.org/10.1111/j.1600-0854.2009.00895.x CrossRefPubMed

62.

Moran LB, Duke DC, Deprez M, Dexter DT, Pearce RKB, Graeber MB (2006) Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson’s disease. Neurogenetics 7:1–11. https://doi.org/10.1007/s10048-005-0020-2 CrossRefPubMed

63.

Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D et al (2019) Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol 18:1091–1102. https://doi.org/10.1016/S1474-4422(19)30320-5 CrossRefPubMedPubMedCentral

64.

Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M et al (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 46:989–993. https://doi.org/10.1038/ng.3043 CrossRefPubMedPubMedCentral

65.

Nalls MA, Saad M, Noyce AJ, Keller MF, Schrag A, Bestwick JP et al (2014) Genetic comorbidities in Parkinson’s disease. Hum Mol Genet 23:831–841. https://doi.org/10.1093/hmg/ddt465 CrossRefPubMed

66.

Noyce AJ, Bandres-Ciga S, Kim J, Heilbron K, Kia D, Hemani G et al (2019) The Parkinson’s Disease Mendelian Randomization Research Portal. bioRxiv 2019:604033. https://doi.org/10.1101/604033

67.

Olsen JH, Friis S, Frederiksen K (2006) Malignant melanoma and other types of cancer preceding Parkinson disease. Epidemiology 17:582–587. https://doi.org/10.1097/01.ede.0000229445.90471.5e CrossRefPubMed

68.

Ong EL, Goldacre R, Goldacre M (2014) Differential risks of cancer types in people with Parkinson’s disease: a national record-linkage study. Eur J Cancer 50:2456–2462. https://doi.org/10.1016/j.ejca.2014.06.018 CrossRefPubMed

69.

Ono K, Viet CT, Ye Y, Dang D, Hitomi S, Toyono T et al (2017) Cutaneous pigmentation modulates skin sensitivity via tyrosinase-dependent dopaminergic signalling. Sci Rep. https://doi.org/10.1038/s41598-017-09682-4 CrossRefPubMedPubMedCentral

70.

Panman L, Papathanou M, Laguna A, Oosterveen T, Volakakis N, Acampora D et al (2014) Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons. Cell Rep 8:1018–1025. https://doi.org/10.1016/j.celrep.2014.07.016 CrossRefPubMed

71.

Pathak MM, Nourse JL, Tran T, Hwe J, Arulmoli J, Le DTT et al (2014) Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc Natl Acad Sci USA 111:16148–16153. https://doi.org/10.1073/pnas.1409802111 CrossRefPubMedPubMedCentral

72.

Perna D, Karreth FA, Rust AG, Perez-Mancera PA, Rashid M, Iorio F et al (2015) BRAF inhibitor resistance mediated by the AKT pathway in an oncogenic BRAF mouse melanoma model. PNAS 112:E536–E545. https://doi.org/10.1073/pnas.1418163112 CrossRefPubMedPubMedCentral

73.

Pividori M, Rajagopal PS, Barbeira A, Liang Y, Melia O, Bastarache L et al (2019) PhenomeXcan: mapping the genome to the phenome through the transcriptome. bioRxiv 2019:833210. https://doi.org/10.1101/833210

74.

Ramasamy A, Trabzuni D, Guelfi S, Varghese V, Smith C, Walker R et al (2014) Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat Neurosci 17:1418–1428. https://doi.org/10.1038/nn.3801 CrossRefPubMedPubMedCentral

75.

Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G (2016) Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis. Neurology 86:566–576. https://doi.org/10.1212/WNL.0000000000002350 CrossRefPubMed

76.

Satoh K, Hata M, Takahara S, Tsuzaki H, Yokota H, Akatsu H et al (2006) A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes. Brain Res 1108:19–27. https://doi.org/10.1016/j.brainres.2006.06.050 CrossRefPubMed

77.

Scott O, Pugh J, Kiddoo D, Sonnenberg LK, Bamforth S, Goez HR (2014) Global developmental delay, progressive relapsing-remitting parkinsonism, and spinal syrinx in a child with SOX6 mutation. J Child Neurol. https://doi.org/10.1177/0883073813514134 CrossRefPubMed

78.

Scrivens PJ, Shahrzad N, Moores A, Morin A, Brunet S, Sacher M (2009) TRAPPC2L is a novel, highly conserved TRAPP-interacting protein. Traffic 10:724–736. https://doi.org/10.1111/j.1600-0854.2009.00906.x CrossRefPubMed

79.

Segel M, Neumann B, Hill MFE, Weber IP, Viscomi C, Zhao C et al (2019) Niche stiffness underlies the ageing of central nervous system progenitor cells. Nature. https://doi.org/10.1038/s41586-019-1484-9 CrossRefPubMedPubMedCentral

80.

Skibba JL, Pinckley J, Gilbert EF, Johnson RO (1972) Multiple primary melanoma following administration of levodopa. Arch Pathol 93:556–561PubMed

81.

Tacik P, Curry S, Fujioka S, Strongosky A, Uitti RJ, van Gerpen JA et al (2016) Cancer in Parkinson’s disease. Parkinsonism Relat Disord 31:28–33. https://doi.org/10.1016/j.parkreldis.2016.06.014 CrossRefPubMedPubMedCentral

82.

Takatsu H, Nishida H, Matsuo H, Watanabe S, Nagashima K, Wada H et al (2000) Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG. J Nucl Med 41:71–77PubMed

83.

Tell-Marti G, Puig-Butille JA, Potrony M, Badenas C, Milà M, Malvehy J et al (2015) The MC1R melanoma risk variant p. R160W is associated with Parkinson disease. Ann Neurol 77:889–894. https://doi.org/10.1002/ana.24373 CrossRefPubMed

84.

The 1000 Genomes Project Consortium (2015) A global reference for human genetic variation. Nature 526:68–74. https://doi.org/10.1038/nature15393 CrossRef

85.

Tsukita K, Sakamaki‐Tsukita H, Tanaka K, Suenaga T, Takahashi R (2019) Value of in vivo α-synuclein deposits in Parkinson’s disease: a systematic review and meta-analysis. Movement Disord. https://doi.org/10.1002/mds.27794 CrossRefPubMed

86.

Ueda R, Yoshida K, Kawakami Y, Kawase T, Toda M (2004) Expression of a transcriptional factor, SOX6, in human gliomas. Brain Tumor Pathol 21:35–38. https://doi.org/10.1007/BF02482175 CrossRefPubMed

87.

Walter U, Heilmann E, Voss J, Riedel K, Zhivov A, Schäd SG et al (2015) Frequency and profile of Parkinson’s disease prodromi in patients with malignant melanoma. J Neurol Neurosurg Psychiatry jnnp-2014-310239. https://doi.org/10.1136/jnnp-2014-310239 CrossRef

88.

Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164. https://doi.org/10.1093/nar/gkq603 CrossRefPubMedPubMedCentral

89.

Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H et al (2014) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42:D1001–1006. https://doi.org/10.1093/nar/gkt1229 CrossRefPubMed

90.

Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26:2190–2191. https://doi.org/10.1093/bioinformatics/btq340 CrossRefPubMedPubMedCentral

91.

Wirdefeldt K, Weibull CE, Chen H, Kamel F, Lundholm C, Fang F et al (2014) Parkinson’s disease and cancer: a register-based family study. Am J Epidemiol 179:85–94. https://doi.org/10.1093/aje/kwt232 CrossRefPubMed

92.

Zhang T, Choi J, Kovacs MA, Shi J, Xu M, Program NCS et al (2018) Cell-type–specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes. Genome Res. https://doi.org/10.1101/gr.233304.117 CrossRefPubMedPubMedCentral

93.

GTEx Consortium (2015) The Genotype-tissue expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348:648–660. https://doi.org/10.1126/science.1262110 CrossRefPubMedCentral

Titel: Overlapping genetic architecture between Parkinson disease and melanoma
verfasst von: Umber Dube
Laura Ibanez
John P. Budde
Bruno A. Benitez
Albert A. Davis
Oscar Harari
Mark M. Iles
Matthew H. Law
Kevin M. Brown
Carlos Cruchaga
23andMe Research Team
Melanoma-Meta-analysis Consortium
Publikationsdatum: 01.02.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 2/2020
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-02110-z

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2020

The active contribution of OPCs to neuroinflammation is mediated by LRP1

Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials

Loss of fragile X mental retardation protein precedes Lewy pathology in Parkinson’s disease

Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study

[18F]Flortaucipir distinguishes Alzheimer’s disease from progressive supranuclear palsy pathology in a mixed-pathology case