Mutations

MAPT c.-18+22596C>T (rs17649553)

Other Names: rs17649553

Overview

Pathogenicity: Parkinson's Disease : Not Classified, Alzheimer's Disease : Not Classified, Dementia with Lewy Bodies : Not Classified
Position: (GRCh38/hg38):Chr17:45917282 C>T
Position: (GRCh37/hg19):Chr17:43994648 C>T
dbSNP ID: rs17649553
Coding/Non-Coding: Non-Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Intron 1

Findings

This common intronic variant has been studied in the context of several neurodegenerative disorders.  It was first reported as associated with Parkinson’s disease (PD) in a large meta-analysis of genome wide association studies (GWAS) comprising 13,708 patients with PD and 95,282 controls of European ancestry (Nalls et al., 2014; see table below). The study found 28 independent risk loci, including the finding that the minor T allele of c.-18+22596C>T was associated with a significantly lower risk of PD than the C allele. A subsequent GWAS study of 235 PD and 464 control individuals from Cyprus also found a reduced risk of PD associated with the T allele, but the association’s statistical significance was nominal and did not survive Bonferroni correction (Georgiou et al., 2019). In both studies, the odds ratios were between 0.7-0.8. Moreover, a GWAS of 240 patients with PD and 192 control individuals from Southern Spain also revealed a marginal association that did not reach statistical significance (Bandrés-Ciga et al., 2016). A larger follow-up study from Southern Spain (738 patients with PD and 1,138 healthy controls) supported an association with reduced PD risk based on outcomes of rs9468, which is in perfect linkage disequilibrium with c.-18+22596C>T (Tejera-Parrado et al., 2019).

The association of c.-18+22596C>T with cognitive function amongst patients with PD has also been examined in patients from the Parkinson’s Progression Markers Initiative (PPMI) cohort. In a study of 423 patients with newly diagnosed PD, c.-18+22596C>T was not predictive of cognitive impairment over the course of a 3-year study (Caspell-Garcia et al., 2017). However, another study of 83 PD patients from the PPMI reported the T allele being a predictor for better verbal memory (Chen et al., 2023).

To assess whether c.-18+22596C>T was associated with Alzheimer’s disease (AD), researchers conducted a GWAS study in a Chinese Han population of 992 patients with sporadic late-onset AD and 1,358 controls (Zhu et al., 2017). However, no significant association was found. In a more recent study of the AD Neuroimaging Initiative genetic cohort, authors segregated patients with AD into three clusters based on genetics and a brain-specific protein–protein interaction network (Hernández-Lorenzo et al., 2024). One of the clusters generated was driven in large part by c.-18+22596C>T. Although symptoms and pathology were generally similar between clusters, these findings suggest that distinct biological mechanisms may be driving disease across the clusters. Thus, while c.-18+22596C>T does not seem to affect AD risk, it contributed to subgrouping of AD based on genetics and pathophysiological and symptomatological features.

Finally, to assess the link between c.-18+22596C>T and dementia with Lewy bodies, a GWAS study of 1,743 patients and 4,454 controls who were White and of European ancestry was conducted, but c.-18+22596C>T was not found to be significantly associated with the disease (Guerreiro et al., 2018).

The global allele frequency of this variant in the gnomAD variant database is 0.14 (gnomAD, v4.1.0, Nov 2024). Although the variant is found in all ancestry groups reported in the gnomAD, frequencies are highest in individuals of Amish, Ashkenazi Jewish, European (non-Finnish), and Middle Eastern ancestry (0.22-0.28), while the frequency is much lower in East Asians  (0.001543).

Neuropathology
The association of c.-18+22596C>T with several neuropathological features has been examined in patients with PD. For example, one study found gray and white matter networks to be altered in CT/TT carriers versus CC carriers of the c.-18+22596C>T SNP, and these changes were correlated with better verbal memory (Chen et al., 2023).

Molecular outcomes associated with c.-18+22596C>T have also been examined in PD, yielding negative results. In a study of 150 patients with PD from PPMI, for example, c.-18+22596C>T was not linked to declining dopamine transporter availability in the caudate nucleus or putamen over disease course (Shin et al., 2019). c.-18+22596C>T was also not associated with total or phosphorylated tau levels in the cerebrospinal fluid based on data from the study population used in Nalls et al., 2014 (i.e., 829 patients with PD and 432 controls of European ancestry; Ibanez et al., 2017).

The c.-18+22596C>T SNP has also been examined for its potential effects on cellular and molecular outcomes in Lewy body disease.  c.-18+22596C>T was not associated with nigrostriatal degeneration as measured by tyrosine hydroxylase immunoreactivity in the dorsolateral or ventromedial putamen in patients (n=492) with Lewy body pathology (with or without parkinsonism) from the Mayo Clinic in Jacksonville, Florida (Kasanuki et al., 2017). Lewy body counts were also not significantly associated (after adjusting for multiple comparisons) with c.-18+22596C>T in a study of 547 patients with Lewy body disease (Heckman et al., 2017).

Biological Effect
The biological effect of c.-18+22596C>T is unknown, but one study suggests it may regulate the expression of genes neighboring MAPT on chromosome 17. T allele carriers (CT/TT) of c.-18+22596C>T had higher expression levels of a transcribed noncoding element of KANSL1 and reduced expression of the pseudogene LRRC37A4P in laser-captured dopamine neurons and temporal cortex pyramidal neurons, compared to individuals with the CC genotype (Dong et al., 2018; Oct 2018 news). KANSL1 is important for normal brain function, and microdeletions in it lead to Koolen de Vries syndrome, a condition characterized by severe learning disabilities and developmental delays. 

This variant’s PHRED-scaled CADD score (0.25), which integrates diverse information in silico was well below 20, the commonly used threshold to predict deleteriousness (CADD v1.6, Nov 2024).

Table

Allelic Associations between c.-18+22596C>T and Neurodegenerative Disorders

Disease Risk Allele(s) Risk Allele Freq.
Cases | Controls		 N
Cases | Controls		 Association Results Ancestry Reference
PD T 0.23 Discovery phasea:
13,708 | 95,282

Replication phasea:
5,353 | 5,551

 OR=0.77
p=4.86×10-37

 

OR=0.76
p=7.03×10-15

 European Nalls et al., 2014
PD T   235 | 464 ORb=0.71
CI=0.54-0.93
p=0.013		 Greek-Cypriot Georgiou et al., 2019
PD T 0.31 240 | 192

OR=0.63
CI= 0.42-0.95
 

 Southern Spanish Bandrés-Ciga et al., 2016
AD  T 0.10|0.18 1,982|2,711 OR=0.63
CI=0.12-3.25
p>1		 Chinese Han Zhu et al., 2017
DLB     1,743 | 4,454 OR=0.86
CI=0.76-0.97
p=0.013		 European Guerreiro et al., 2018

aMeta-analysis
bp-value nominal significance threshold = 0.05; Bonferroni adjusted significance threshold=0.004

This table is meant to convey the range of results reported in the literature. As specific analyses, including co-variates, differ among studies, this information is not intended to be used for quantitative comparisons, and readers are encouraged to refer to the original papers. Thresholds for statistical significance were defined by the authors of each study. (Significant results are in bold.) Note that data from some cohorts may have contributed to multiple studies, so each row does not necessarily represent an independent dataset. While every effort was made to be accurate, readers should confirm any values that are critical for their applications.

Last Updated: 12 Nov 2024

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References

News Citations

  1. Noncoding RNAs Evince World of Gene Regulation in Dopaminergic Neurons

Paper Citations

  1. Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R, International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Ashkenazi Jewish Dataset Investigator, Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE), North American Brain Expression Consortium (NABEC), United Kingdom Brain Expression Consortium (UKBEC), Greek Parkinson's Disease Consortium, Alzheimer Genetic Analysis Group, Ikram MA, Ioannidis JP, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet. 2014 Sep;46(9):989-93. Epub 2014 Jul 27 PubMed.
  2. Georgiou A, Demetriou CA, Christou YP, Heraclides A, Leonidou E, Loukaides P, Yiasoumi E, Pantziaris M, Kleopa KA, Papacostas SS, Loizidou MA, Hadjisavvas A, Zamba-Papanicolaou E. Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population. Front Neurol. 2019;10:1047. Epub 2019 Oct 17 PubMed.
  4. Tejera-Parrado C, Jesús S, Periñán MT, Buiza-Rueda D, Oliva-Ariza G, Adarmes-Gómez AD, Macías-García D, Gómez-Garre P, Mir P. A replication study of GWAS-genetic risk variants associated with Parkinson's disease in a Spanish population. Neurosci Lett. 2019 Nov 1;712:134425. Epub 2019 Aug 17 PubMed.
  5. Caspell-Garcia C, Simuni T, Tosun-Turgut D, Wu IW, Zhang Y, Nalls M, Singleton A, Shaw LA, Kang JH, Trojanowski JQ, Siderowf A, Coffey C, Lasch S, Aarsland D, Burn D, Chahine LM, Espay AJ, Foster ED, Hawkins KA, Litvan I, Richard I, Weintraub D, Parkinson’s Progression Markers Initiative (PPMI). Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 2017;12(5):e0175674. Epub 2017 May 17 PubMed.
  6. Chen Z, Wu B, Li G, Zhou L, Zhang L, Liu J. MAPT rs17649553 T allele is associated with better verbal memory and higher small-world properties in Parkinson's disease. Neurobiol Aging. 2023 Sep;129:219-231. Epub 2023 Jun 12 PubMed.
  7. Zhu XC, Cao L, Tan MS, Jiang T, Wang HF, Lu H, Tan CC, Zhang W, Tan L, Yu JT. Association of Parkinson's Disease GWAS-Linked Loci with Alzheimer's Disease in Han Chinese. Mol Neurobiol. 2017 Jan;54(1):308-318. Epub 2016 Jan 6 PubMed.
  8. Hernández-Lorenzo L, García-Gutiérrez F, Solbas-Casajús A, Corrochano S, Matías-Guiu JA, Ayala JL. Genetic-based patient stratification in Alzheimer's disease. Sci Rep. 2024 Apr 30;14(1):9970. PubMed. Correction.
  9. Guerreiro R, Ross OA, Kun-Rodrigues C, Hernandez DG, Orme T, Eicher JD, Shepherd CE, Parkkinen L, Darwent L, Heckman MG, Scholz SW, Troncoso JC, Pletnikova O, Ansorge O, Clarimon J, Lleo A, Morenas-Rodriguez E, Clark L, Honig LS, Marder K, Lemstra A, Rogaeva E, St George-Hyslop P, Londos E, Zetterberg H, Barber I, Braae A, Brown K, Morgan K, Troakes C, Al-Sarraj S, Lashley T, Holton J, Compta Y, Van Deerlin V, Serrano GE, Beach TG, Lesage S, Galasko D, Masliah E, Santana I, Pastor P, Diez-Fairen M, Aguilar M, Tienari PJ, Myllykangas L, Oinas M, Revesz T, Lees A, Boeve BF, Petersen RC, Ferman TJ, Escott-Price V, Graff-Radford N, Cairns NJ, Morris JC, Pickering-Brown S, Mann D, Halliday GM, Hardy J, Trojanowski JQ, Dickson DW, Singleton A, Stone DJ, Bras J. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018 Jan;17(1):64-74. Epub 2017 Dec 16 PubMed.
  10. Shin S, Kim K, Lee JM, Kim EJ, Kim SJ, Kim IJ, Pak K, Lee MJ. Effect of Single-Nucleotide Polymorphisms on Decline of Dopamine Transporter Availability in Parkinson's Disease. J Clin Neurol. 2019 Jan;15(1):102-107. PubMed.
  11. Ibanez L, Dube U, Saef B, Budde J, Black K, Medvedeva A, Del-Aguila JL, Davis AA, Perlmutter JS, Harari O, Benitez BA, Cruchaga C. Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels. BMC Neurol. 2017 Nov 15;17(1):198. PubMed.
  12. Kasanuki K, Heckman MG, Diehl NN, Murray ME, Koga S, Soto A, Ross OA, Dickson DW. Regional analysis and genetic association of nigrostriatal degeneration in Lewy body disease. Mov Disord. 2017 Nov;32(11):1584-1593. Epub 2017 Sep 26 PubMed.
  13. Heckman MG, Kasanuki K, Diehl NN, Koga S, Soto A, Murray ME, Dickson DW, Ross OA. Parkinson's disease susceptibility variants and severity of Lewy body pathology. Parkinsonism Relat Disord. 2017 Nov;44:79-84. Epub 2017 Sep 11 PubMed.
  14. Dong X, Liao Z, Gritsch D, Hadzhiev Y, Bai Y, Locascio JJ, Guennewig B, Liu G, Blauwendraat C, Wang T, Adler CH, Hedreen JC, Faull RL, Frosch MP, Nelson PT, Rizzu P, Cooper AA, Heutink P, Beach TG, Mattick JS, Müller F, Scherzer CR. Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nat Neurosci. 2018 Oct;21(10):1482-1492. Epub 2018 Sep 17 PubMed.

Further Reading

Papers

  1. Chairta PP, Hadjisavvas A, Georgiou AN, Loizidou MA, Yiangou K, Demetriou CA, Christou YP, Pantziaris M, Michailidou K, Zamba-Papanicolaou E. Prediction of Parkinson's Disease Risk Based on Genetic Profile and Established Risk Factors. Genes (Basel). 2021 Aug 20;12(8) PubMed.
  2. Chang D, Nalls MA, Hallgrímsdóttir IB, Hunkapiller J, van der Brug M, Cai F, International Parkinson's Disease Genomics Consortium, 23andMe Research Team, Kerchner GA, Ayalon G, Bingol B, Sheng M, Hinds D, Behrens TW, Singleton AB, Bhangale TR, Graham RR. A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nat Genet. 2017 Oct;49(10):1511-1516. Epub 2017 Sep 11 PubMed.
  3. Cooper CA, Jain N, Gallagher MD, Weintraub D, Xie SX, Berlyand Y, Espay AJ, Quinn J, Edwards KL, Montine T, Van Deerlin VM, Trojanowski J, Zabetian CP, Chen-Plotkin AS. Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype. Ann Clin Transl Neurol. 2017 Jan;4(1):15-25. Epub 2016 Nov 25 PubMed.
  4. Fadason T, Schierding W, Lumley T, O'Sullivan JM. Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities. Nat Commun. 2018 Dec 5;9(1):5198. PubMed.
  5. Gu L, Guan X, Gao T, Zhou C, Yang W, Lv D, Wu J, Fang Y, Guo T, Song Z, Xu X, Tian J, Yin X, Zhang M, Zhang B, Pu J, Yan Y. The effect of polygenic risk on white matter microstructural degeneration in Parkinson's disease: A longitudinal Diffusion Tensor Imaging study. Eur J Neurol. 2022 Apr;29(4):1000-1010. Epub 2021 Dec 21 PubMed.
  6. Han Z, Tian R, Ren P, Zhou W, Wang P, Luo M, Jin S, Jiang Q. Parkinson's disease and Alzheimer's disease: a Mendelian randomization study. BMC Med Genet. 2018 Dec 31;19(Suppl 1):215. PubMed.
  7. Jansen IE, Gibbs JR, Nalls MA, Price TR, Lubbe S, van Rooij J, Uitterlinden AG, Kraaij R, Williams NM, Brice A, Hardy J, Wood NW, Morris HR, Gasser T, Singleton AB, Heutink P, Sharma M, International Parkinson's Disease Genomics Consortium. Establishing the role of rare coding variants in known Parkinson's disease risk loci. Neurobiol Aging. 2017 Nov;59:220.e11-220.e18. Epub 2017 Aug 2 PubMed.
  8. Lai MC, Bechy AL, Denk F, Collins E, Gavriliouk M, Zaugg JB, Ryan BJ, Wade-Martins R, Caffrey TM. Haplotype-specific MAPT exon 3 expression regulated by common intronic polymorphisms associated with Parkinsonian disorders. Mol Neurodegener. 2017 Oct 30;12(1):79. PubMed.
  9. Manzoni C, Kia DA, Ferrari R, Leonenko G, Costa B, Saba V, Jabbari E, Tan MM, Albani D, Alvarez V, Alvarez I, Andreassen OA, Angiolillo A, Arighi A, Baker M, Benussi L, Bessi V, Binetti G, Blackburn DJ, Boada M, Boeve BF, Borrego-Ecija S, Borroni B, Bråthen G, Brooks WS, Bruni AC, Caroppo P, Bandres-Ciga S, Clarimon J, Colao R, Cruchaga C, Danek A, de Boer SC, de Rojas I, di Costanzo A, Dickson DW, Diehl-Schmid J, Dobson-Stone C, Dols-Icardo O, Donizetti A, Dopper E, Durante E, Ferrari C, Forloni G, Frangipane F, Fratiglioni L, Kramberger MG, Galimberti D, Gallucci M, García-González P, Ghidoni R, Giaccone G, Graff C, Graff-Radford NR, Grafman J, Halliday GM, Hernandez DG, Hjermind LE, Hodges JR, Holloway G, Huey ED, Illán-Gala I, Josephs KA, Knopman DS, Kristiansen M, Kwok JB, Leber I, Leonard HL, Libri I, Lleo A, Mackenzie IR, Madhan GK, Maletta R, Marquié M, Maver A, Menendez-Gonzalez M, Milan G, Miller BL, Morris CM, Morris HR, Nacmias B, Newton J, Nielsen JE, Nilsson C, Novelli V, Padovani A, Pal S, Pasquier F, Pastor P, Perneczky R, Peterlin B, Petersen RC, Piguet O, Pijnenburg YA, Puca AA, Rademakers R, Rainero I, Reus LM, Richardson AM, Riemenschneider M, Rogaeva E, Rogelj B, Rollinson S, Rosen H, Rossi G, Rowe JB, Rubino E, Ruiz A, Salvi E, Sanchez-Valle R, Sando SB, Santillo AF, Saxon JA, Schlachetzki JC, Scholz SW, Seelaar H, Seeley WW, Serpente M, Sorbi S, Sordon S, St George-Hyslop P, Thompson JC, Van Broeckhoven C, Van Deerlin VM, Van der Lee SJ, Van Swieten J, Tagliavini F, van der Zee J, Veronesi A, Vitale E, Waldo ML, Yokoyama JS, Nalls MA, Momeni P, Singleton AB, Hardy J, Escott-Price V. Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia. Am J Hum Genet. 2024 Jul 11;111(7):1316-1329. Epub 2024 Jun 17 PubMed.
  10. Mollenhauer B, Dakna M, Kruse N, Galasko D, Foroud T, Zetterberg H, Schade S, Gera RG, Wang W, Gao F, Frasier M, Chahine LM, Coffey CS, Singleton AB, Simuni T, Weintraub D, Seibyl J, Toga AW, Tanner CM, Kieburtz K, Marek K, Siderowf A, Cedarbaum JM, Hutten SJ, Trenkwalder C, Graham D. Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression. Mov Disord. 2020 Nov;35(11):1999-2008. Epub 2020 Aug 15 PubMed.
  11. Rikos D, Siokas V, Burykina TI, Drakoulis N, Dardiotis E, Zintzaras E. Replication of chromosomal loci involved in Parkinson's disease: A quantitative synthesis of GWAS. Toxicol Rep. 2021;8:1762-1768. Epub 2021 Oct 12 PubMed.
  12. Sampedro F, Marín-Lahoz J, Martínez-Horta S, Pagonabarraga J, Kulisevsky J. Early Gray Matter Volume Loss in MAPT H1H1 de Novo PD Patients: A Possible Association With Cognitive Decline. Front Neurol. 2018;9:394. Epub 2018 May 30 PubMed.
  13. Chen Z, Wu B, Li G, Zhou L, Zhang L, Liu J. Parkinson's disease-associated genetic variants synergistically shape brain networks. 2023 Jun 26 10.1101/2022.12.25.22283938 (version 3) medRxiv.
  14. Sugier PE, Lucotte EA, Domenighetti C, Law MH, Iles MM, Brown K, Amos C, McKay JD, Hung RJ, Karimi M, Bacq-Daian D, Boland-Augé A, Olaso R, Deleuze JF, Lesueur F, Ostroumova E, Kesminiene A, de Vathaire F, Guénel P, EPITHYR consortium, Sreelatha AA, Schulte C, Grover S, May P, Bobbili DR, Radivojkov-Blagojevic M, Lichtner P, Singleton AB, Hernandez DG, Edsall C, Mellick GD, Zimprich A, Pirker W, Rogaeva E, Lang AE, Koks S, Taba P, Lesage S, Brice A, Corvol JC, Chartier-Harlin MC, Mutez E, Brockmann K, Deutschländer AB, Hadjigeorgiou GM, Dardiotis E, Stefanis L, Simitsi AM, Valente EM, Petrucci S, Straniero L, Zecchinelli A, Pezzoli G, Brighina L, Ferrarese C, Annesi G, Quattrone A, Gagliardi M, Matsuo H, Nakayama A, Hattori N, Nishioka K, Chung SJ, Kim YJ, Kolber P, van de Warrenburg BP, Bloem BR, Aasly J, Toft M, Pihlstrøm L, Guedes LC, Ferreira JJ, Bardien S, Carr J, Tolosa E, Ezquerra M, Pastor P, Diez-Fairen M, Wirdefeldt K, Pedersen N, Ran C, Belin AC, Puschmann A, Rödström EY, Clarke CE, Morrison KE, Tan M, Krainc D, Burbulla LF, Farrer MJ, Kruger R, Gasser T, Sharma M, Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) consortium, Truong T, Elbaz A. Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers. Mov Disord. 2023 Apr;38(4):604-615. Epub 2023 Feb 14 PubMed.
  15. Won JH, Youn J, Park H. Enhanced neuroimaging genetics using multi-view non-negative matrix factorization with sparsity and prior knowledge. Med Image Anal. 2022 Apr;77:102378. Epub 2022 Jan 29 PubMed.
  16. Almgren H, Camacho M, Hanganu A, Kibreab M, Camicioli R, Ismail Z, Forkert ND, Monchi O. Machine learning-based prediction of longitudinal cognitive decline in early Parkinson's disease using multimodal features. Sci Rep. 2023 Aug 14;13(1):13193. PubMed.

Protein Diagram

Primary Papers

  1. Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R, International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Ashkenazi Jewish Dataset Investigator, Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE), North American Brain Expression Consortium (NABEC), United Kingdom Brain Expression Consortium (UKBEC), Greek Parkinson's Disease Consortium, Alzheimer Genetic Analysis Group, Ikram MA, Ioannidis JP, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet. 2014 Sep;46(9):989-93. Epub 2014 Jul 27 PubMed.

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