Using global team science to identify genetic Parkinson's disease worldwide.

Fue publicado el artículo en el que participa Uruguay:

Ann Neurol. 2019 Jun 2. doi: 10.1002/ana.25514. [Epub ahead of print]

Using global team science to identify genetic Parkinson's disease worldwide.

Vollstedt EJ1, Kasten M1,2, Klein C1; MJFF Global Genetic Parkinson's Disease Study Group.

Collaborators (209)
Aasly J, Adler C, Ahmad-Annuar A, Albanese A, Alcalay R, Al-Mubarak B, Alvarez V, Andree-Muñoz B, Annesi G, Appel-Cresswell S, Arkadir D, Armasu S, Barber TR, Bardien S, Barkhuizen M, Barrett MJ, BaŞak AN, Beach T, Benitez BA, Berg D, Bhatia K, Binkofski F, Blauwendraat C, Bonifati V, Borges V, Bozi M, Brice A, Brighina L, Brockmann K, Brüggemann N, Camacho M, Cardoso F, Belin AC, Carr J, Chan P, Chang-Castello J, Chase B, Chen-Plotkin A, Chung SJ, Cilia R, Clarimon J, Clark L, Cornejo-Olivas M, Corvol JC, Cosentino C, Cras P, Crosiers D, Damásio J, Das P, de Carvalho Aguiar P, De Michele G, De Rosa A, Dieguez E, Dorszewska J, Erer S, Ertan S, Farrer M, Fedotova E, Ferese R, Ferrarese C, Ferraz H, Fiala O, Foroud T, Friedman A, Frigerio R, Funayama M, Gambardella S, Garraux G, Gatto EM, Genç G, Goldwurm S, Gomez-Esteban JC, Gómez-Garre P, Gorostidi A, Grosset D, Hanagasi H, Hardy J, Hassan A, Hattori N, Hauser RA, Hedera P, Hentati F, Hertz JM, Holton JL, Houlden H, Hutz MH, Ikeuchi T, Illarioshkin S, Inca-Martinez M, Infante J, Jankovic J, Jeon BS, Jesús S, Jimenez-Del-Rio M, Kasten M, Kataoka H, Kawakami H, Kim YJ, Klein C, Klivényi P, Koks S, König IR, KostiĆ V, Koziorowski D, Krüger R, Krygowska-Wajs A, Kulisevsky J, Lang A, LeDoux M, Lesage S, Lim SY, Lin CH, Lohmann K, Lopera F, Lopez G, Lu CS, Lynch T, Machaczka M, Madoev H, Magalhães M, Majamaa K, Maraganore D, Marder K, Markopoulou K, Martikainen MH, Mata I, Mazzetti P, Mellick G, Menéndez-González M, Micheli F, Mirelman A, Mir P, Morino H, Morris H, Munhoz RP, Naito A, Olszewska DA, Ozelius LJ, Padmanabhan S, Paisán-Ruiz C, Payami H, Peluso S, Petkovic S, Petrucci S, Pezzoli G, Pimentel M, Pirker W, Pramstaller PP, Pulkes T, Puschmann A, Quattrone A, Raggio V, Ransmayr G, Rieder C, Riess O, Rodriguez-Porcel F, Rogaeva E, Ross OA, Ruiz-Martinez J, Sammler E, Luciano MS, Satake W, Saunders-Pullman R, Sazci A, Scherzer C, Schrag A, Schumacher-Schuh A, Sharma M, Sidransky E, Singleton AB, Petersen MS, Smolders S, Spitz M, Stefanis L, Struhal W, Sue C, Swan M, Swanberg M, Taba P, Taipa R, Tan M, Tan AH, Tan EK, Tang B, Tayebi N, Thaler A, Thomas A, Toda T, Toft M, Torres L, Tumas V, Valente EM, Van Broeckhoven C, Vecsei L, Velez-Pardo C, Vidailhet M, Vollstedt EJ, Warner TT, Williams-Gray CH, Winkelmann J, Woitalla D, Wood NW, Wszolek ZK, Wu RM, Wu YR, Xie T, Yoshino H, Zhang B, Zimprich A.

Author information
1
Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
2
Department of Psychiatry, University of Luebeck, Luebeck, Germany.


https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25514

Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry

Salió la publicación con los resultados de LARGE-PD para mutaciones en LRRK2 en Latinoamérica del que somos participantes. A continuación tienen el resumen y siguiendo el link se accede al artículo completo.


Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry

Mario Cornejo-Olivas1,2, Luis Torres3,4, Mario R. Velit-Salazar1,5, Miguel Inca-Martinez1, Pilar Mazzetti1,4, Carlos Cosentino3,4,Federico Micheli6, Claudia Perandones6, Elena Dieguez7, Victor Raggio8, Vitor Tumas9, Vanderci Borges10, Henrique B. Ferraz10,Carlos R. M. Rieder11, Artur Shumacher-Schuh11, Carlos Velez-Pardo12, Marlene Jimenez-Del-Rio12, Francisco Lopera12,Jorge Chang-Castello13, Brennie Andreé-Munoz14, Sarah Waldherr15,16, Dora Yearout15,16, Cyrus P. Zabetian15,16and Ignacio F. Mata15,16

1Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru;2Northern Pacific Global Health Research Training Consortium, Bethesda, MD, USA;3Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru;4Universidad Nacional Mayor de San Marcos, Lima, Peru;5Universidad Peruana CayetanoHeredia, Lima, Peru;6Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina;7Neurology Institute, Universidad de la Republica,Montevideo, Uruguay;8Department of Genetics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay;9Ribeirão Preto Medical School, Universidade de SãoPaulo, Ribeirão Preto, Brazil;10Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, SP, Brazil;11Hospital deClínicas de Porto Alegre, Porto Alegre, Brazil;12Neruroscience Research Group, Medical Research Institute, Universidad de Antioquia, Medellin, Colombia;13Department ofGenetics, School of Medici ne, Universidad de Guayaquil, Hospital Luis Vernaza, Guayaquil, Ecuador;14Service of Neurology, Hospital Luis Vernaza, Guayaquil, Ecuador;15VeteransAffairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA and16Department of Neurology, University of Washington, Seattle, WA, USACorrespondence: Ignacio F . Mata (nachofm@uw.edu)

Mutations in Leucine Repeat Rich Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson’s disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson’s disease, but this finding requires replication. We screened1734 Parkinson’s disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson’s disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson’s disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson’s disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common.
npj Parkinson’s Disease  (2017) 3:19  ; doi:10.1038/s41531-017-0020-6

http://rdcu.be/tb39

Genética de la EP desde Seattle

The Power to be Precise
Cyrus Zabetian e Ignacio Fernandez Mata.

Un muy buen artículo sobre los últimos trabajos de este grupo con quienes tenemos el gusto de colaborar.

El artículo original recientemente publicado: GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease. 

Parkinson’s disease: From human genetics to clinical trials

Parkinson’s disease: From human genetics to clinical trials

Marcel P. van der Brug1, Andrew Singleton2, Thomas Gasser3 and Patrick A. Lewis4,5,6,*

Science Translational Medicine  16 Sep 2015:
Vol. 7, Issue 305, pp. 205ps20
DOI: 10.1126/scitranslmed.aaa8280

New Parkinson's Disease Findings | The 23andMe Blog

New Parkinson's Disease Findings | The 23andMe Blog

BioNews - Call for volunteers for open-access genome project

BioNews - Call for volunteers for open-access genome project

Genética y Enfermedad de Parkinson

Texto resumido de la charla que daré el martes 22/10 en el Hospital de Clínicas en el marco de PRENPAR.


En la charla de hoy me gustaría contarles sobre algunos aspectos generales de la Genética como disciplina y de sus aplicaciones en salud humana. De forma paralela, repasar algunos de los aspectos que hemos visto en varias oportunidades sobre genética y enfermedad de Parkinson (EP).

Herencia y variabilidad

La Genética es el estudio de la herencia y la variabilidad. Empieza analizando el parecido entre parientes, el cual se puede evidenciar tanto en la fisonomía y lo que vulgarmente llamamos el “parecido”, pero también se pueden evidenciar en el parecido en la forma de enfermar o de responder a la medicación. Es sabido que los hijos de un paciente con EP tienen por lo menos el doble de probabilidad de tener ellos la enfermedad, comparados con el resto de la población.
Por otro lado, la Genética, se centra en qué nos hace diferentes. En la variabilidad biológica. La que de nuevo, nos hace diferentes en nuestras susceptibilidades y resistencias a distintas afecciones, además de diferentes como individuos.

Mutaciones

La base molecular de esta variabilidad reside en los cambios del ADN. En las denominadas mutaciones. La gran mayoría de ellas son neutras, las portamos todos sin ninguna consecuencia negativa (e incluso a veces con efectos positivos), pero en algunos casos se convierten en determinantes fuertes de nuestras enfermedades. De hecho, en algunos individuos o familias, una mutación es el principal determinante de su salud, de su calidad de vida y de los cuidados médicos (y de otros tipos) que necesiten a lo largo de su vida. Hoy se conocen cientos de mutaciones en más de una decena de genes que pueden causar (o favorecer fuertemente la aparición de) EP.

La Genética y nosotros
La genética está de moda y por ende, vemos mucho de ella en los medios. Por otro lado, tiene mucho que decirnos sobre nosotros mismos, como especie y como individuos. Viejos problemas - como el origen del hombre- se ven hoy con nueva luz gracias a los estudios genómicos. ¿Sabían que todos tenemos algo de ADN de Neanderthal en nuestras células?

La genética y la medicina

Hay ya en el Talmud - compendio de leyes y tradiciones judías, del año 200 DC- descripciones de métodos para prevenir problemas derivados de enfermedades genéticas, en este caso particular, la hemofilia.
Hoy secuenciamos genomas enteros en busca de causas de enfermedades humanas. Se conocen miles de enfermedades causadas por mutaciones en distintos genes. Cada vez se conocen más y más variantes genéticas asociadas a enfermedades humanas y se trata de usar ese conocimiento para diagnosticar, prevenir y tratar las mismas. La EP no es la excepción. En varias oportunidades he mostrado los descubrimientos de genes y mutaciones causales o favorecedores de EP. Algunos de los cuales, incluso, se pueden estudiar en nuestro medio.
En la gran mayoría de los casos (incluida la EP) la relación entre genes y enfermedades no es sencilla. Uno no puede decirle “todo” a un paciente a partir de sus genes. En el mejor de los casos probabilidades o estimaciones para cada caso.

Biotecnología y salud

La ingeniería genética puede permitir desarrollar tratamientos a partir de genes (o fragmentos de genes). Desde 1990 se vienen probando estrategias de terapia génica con distinto grado de éxito. En EP se han iniciado recientemente con resultados potencialmente buenos pero que probablemente llevará tiempo que estén disponibles para nuestro uso.

¿Prevención de enfermedad de Parkinson con estatinas?

Statins protective against Parkinson's: More evidence.

Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson's disease

Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson's disease

Margaux F. Keller1,2, Mohamad Saad3,4, Jose Bras5, Francesco Bettella7, Nayia Nicolaou8, Javier Simón-Sánchez8, Florian Mittag3, Finja Büchel3, Manu Sharma9,10, J. Raphael Gibbs1,5, Claudia Schulte9,10, Valentina Moskvina11,12, Alexandra Durr13,14,15,16, Peter Holmans11,12, Laura L. Kilarski11,12, Rita Guerreiro5, Dena G. Hernandez1,5, Alexis Brice13,14,15,16, Pauli Ylikotila17, Hreinn Stefánsson7, Kari Majamaa18, Huw R. Morris11,12, Nigel Williams11,12, Thomas Gasser9,10, Peter Heutink7, Nicholas W. Wood5,6, John Hardy5, Maria Martinez3,4, Andrew B. Singleton1 and Michael A. Nalls1,* for the International Parkinson's Disease Genomics Consortium (IPDGC) and The Wellcome Trust Case Control Consortium 2 (WTCCC2)†
+ Author Affiliations

1Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA,
2Department of Biological Anthropology, Temple University, Philadelphia, PA, USA,
3Institut National de la Sante et de la Recherche Medicale, UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France,
4Paul Sabatier University, Toulouse, France
5Department of Molecular Neuroscience, Institute of Neurology and
6UCL Genetics Institute, University College London, London, UK
7deCODE genetics, Scientific Services, Sturlugata 8, IS-101 Reykjavik, Iceland,
8Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands,
9Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany,
10Deutsches Zentrum fur Neurodegenerative Erkrangungen (German Center for Neurodegenerative Diseases), Tubingen, Germany
11Institute of Psychological Medicine and Clinical Neurosciences and
12Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
13Université Pierre et Marie Curie-Paris, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, UMR-S975, Paris, France,
14Département de Génétique, AP-HP, Hôpital de la Salpêtrière, Paris, France,
15Institut National de la Sante et de la Recherche Medicale, UMR-S975 (Formerly UMR-S679), Paris, France,
16Centre National de la Recherche Scientifique, UMR-7225, Paris, France,
17Department of Neurology, Turku University Hospital and University of Turku, Finland and
18Department of Clinical Medicine, Neurology, University of Oulu, Finland
↵*To whom correspondence should be addressed at: Molecular Genetics Section, Laboratory of Neurogenetics, NIA, NIH Building 35, 35 Convent Drive, Bethesda, MD 20892, USA. Tel: +1 3014513831; Fax: +1 3014517295; Email: nallsm@mail.nih.gov
Received April 20, 2012.
Revision received July 23, 2012.
Accepted August 1, 2012.
Abstract

Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17–38, P = 8.08E − 08) phenotypic variance associated with all types of PD, 15% (95% CI −0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17–44, P = 1.34E − 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered.

Published by Oxford University Press 2012

TREM2 Variants in Alzheimer's Disease — NEJM

TREM2 Variants in Alzheimer's Disease — NEJM

Large-scale replication and heterogeneity in Parkinson disease genetic loci.

Neurology. 2012 Aug 14;79(7):659-67. doi: 10.1212/WNL.0b013e318264e353. Epub 2012 Jul 11.
Large-scale replication and heterogeneity in Parkinson disease genetic loci.

Sharma M, Ioannidis JP, Aasly JO, Annesi G, Brice A, Van Broeckhoven C, Bertram L, Bozi M, Crosiers D, Clarke C, Facheris M, Farrer M, Garraux G, Gispert S, Auburger G, Vilariño-Güell C, Hadjigeorgiou GM, Hicks AA, Hattori N, Jeon B, Lesage S, Lill CM, Lin JJ, Lynch T, Lichtner P, Lang AE, Mok V, Jasinska-Myga B, Mellick GD, Morrison KE, Opala G, Pramstaller PP, Pichler I, Park SS, Quattrone A, Rogaeva E, Ross OA, Stefanis L, Stockton JD, Satake W, Silburn PA, Theuns J, Tan EK, Toda T, Tomiyama H, Uitti RJ, Wirdefeldt K, Wszolek Z, Xiromerisiou G, Yueh KC, Zhao Y, Gasser T, Maraganore D, Krüger R; GEO-PD Consortium.
Collaborators (103)

Source
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. manu.sharma@uni-tuebingen.de

Abstract
OBJECTIVE:
Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.
METHODS:
Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.
RESULTS:
In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.
CONCLUSION:
Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.

Comment in
Genetic heterogeneity in Parkinson disease: the meaning of GWAS and replication studies. [Neurology. 2012]

Metanálisis de GWAS en EP: nuevo locus, RIT2

Ann Neurol. 2012 Mar;71(3):370-84. doi: 10.1002/ana.22687.

Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2.

Pankratz N, Beecham GW, DeStefano AL, Dawson TM, Doheny KF, Factor SA, Hamza TH, Hung AY, Hyman BT, Ivinson AJ, Krainc D, Latourelle JC, Clark LN, Marder K, Martin ER, Mayeux R, Ross OA, Scherzer CR, Simon DK, Tanner C, Vance JM, Wszolek ZK, Zabetian CP, Myers RH, Payami H, Scott WK, Foroud T; PD GWAS Consortium.
Collaborators (739)

Source
Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Abstract

OBJECTIVE:
Genome-wide association (GWAS) methods have identified genes contributing to Parkinson's disease (PD); we sought to identify additional genes associated with PD susceptibility.

METHODS:
A 2-stage design was used. First, individual level genotypic data from 5 recent PD GWAS (Discovery Sample: 4,238 PD cases and 4,239 controls) were combined. Following imputation, a logistic regression model was employed in each dataset to test for association with PD susceptibility and results from each dataset were meta-analyzed. Second, 768 single-nucleotide polymorphisms (SNPs) were genotyped in an independent Replication Sample (3,738 cases and 2,111 controls).

RESULTS:
Genome-wide significance was reached for SNPs in SNCA (rs356165; G: odds ratio [OR]=1.37; p=9.3×10(-21)), MAPT (rs242559; C: OR=0.78; p=1.5×10(-10)), GAK/DGKQ (rs11248051; T: OR=1.35; p=8.2×10(-9)/rs11248060; T: OR=1.35; p=2.0×10(-9)), and the human leukocyte antigen (HLA) region (rs3129882; A: OR=0.83; p=1.2×10(-8)), which were previously reported. The Replication Sample confirmed the associations with SNCA, MAPT, and the HLA region and also with GBA (E326K; OR=1.71; p=5×10(-8) Combined Sample) (N370; OR=3.08; p=7×10(-5) Replication sample). A novel PD susceptibility locus, RIT2, on chromosome 18 (rs12456492; p=5×10(-5) Discovery Sample; p=1.52×10(-7) Replication sample; p=2×10(-10) Combined Sample) was replicated. Conditional analyses within each of the replicated regions identified distinct SNP associations within GBA and SNCA, suggesting that there may be multiple risk alleles within these genes.

INTERPRETATION:
We identified a novel PD susceptibility locus, RIT2, replicated several previously identified loci, and identified more than 1 risk allele within SNCA and GBA.

Copyright © 2012 American Neurological Association.
PMID: 22451204 [PubMed - indexed for MEDLINE] PMCID: PMC3354734 [Available on 2013/3/1]

Un buen resumen del estado del arte en Investigación en Enfermedad de Parkinson

http://spittoon.23andme.com/2012/04/09/the-state-of-the-science-of-parkinsons-research/

Variantes genéticas asociadas a la Enfermedad de Parkinson - la madre de todas las bases de datos

PDGene.

El artículo en Plos Genetics:
Lill CM , Roehr JT , McQueen MB , Kavvoura FK , Bagade S , et al. (2012) Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database. PLoS Genet 8(3): e1002548. doi:10.1371/journal.pgen.1002548.

LRRK2 Q1111H

Parkinsonism Relat Disord. 2011 May 30. [Epub ahead of print]

Lrrk2 p.Q1111H substitution and Parkinson's disease in Latin America.

Mata IF, Wilhoite GJ, Yearout D, Bacon JA, Cornejo-Olivas M, Mazzetti P, Marca V, Ortega O, Acosta O, Cosentino C, Torres L, Medina AC, Perez-Pastene C, Díaz-Grez F, Vilariño-Güell C, Venegas P, Miranda M, Trujillo-Godoy O, Layson L, Avello R, Dieguez E, Raggio V, Micheli F, Perandones C, Alvarez V, Segura-Aguilar J, Farrer MJ, Zabetian CP, Ross OA.

Source

Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.

Abstract

Mutations in the LRRK2 gene are the most common genetic cause of Parkinson's disease, with frequencies displaying a high degree of population-specificity. Although more than 100 coding substitutions have been identified, only seven have been proven to be highly penetrant pathogenic mutations. Studies however are lacking in non-white populations. Recently, Lrrk2 p.Q1111H (rs78365431) was identified in two affected Hispanic brothers and absent in 386 non-Hispanic white healthy controls. We therefore screened this variant in 1460 individuals (1150 PD patients and 310 healthy controls) from 4 Latin American countries (Peru, Chile, Uruguay and Argentina). In our case-control series from Peru and Chile we observed an increased frequency of Lrrk2 p.Q1111H in patients (7.9%) compared to controls (5.4%) although the difference did not reach significance (OR 1.38; p = 0.10). In addition, the frequency of Lrrk2 p.Q1111H varied greatly between populations and further screening in a set of pure Amerindian and pure Spanish controls suggested that this variant likely originated in an Amerindian population. Further studies in other Latin American populations are warranted to assess its role as a risk factor for Parkinson's disease. Screening in Parkinson's disease patients from under-represented populations will increase our understanding of the role of LRRK2 variants in disease risk worldwide.

Copyright © 2011. Published by Elsevier Ltd.

PMID:

21632271

[PubMed - as supplied by publisher]

Variantes comunes en genes "PARKs" y EP multifactorial: MAPT y SNCA

Chung SJ, Armasu SM, Biernacka JM, Lesnick TG, Rider DN, Lincoln SJ, Ortolaza AI, Farrer MJ, Cunningham JM, Rocca WA, Maraganore DM, Common variants in PARK loci and related genes and Parkinson's disease. Mov Disord. 201;26(2):280-8.

GWAS y metanálisis en EP, más loci

International Parkinson’s Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2) (2011) A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson’s Disease. PLoS Genet 7(6): e1002142. doi:10.1371/journal.pgen.1002142.

Nuevas causas genéticas de EP

Metanálisis de GWAS y fase de replicación, publicado en Lancet (confirma los loci de otros GWAS y encuentra 5 nuevos candidatos).

Hallazgo de una delección en heterocigosis del gene de la Tirosina Hidroxilasa como posible causa de EP, publicado en Human Mutation.

Revisión sobre Genética de la Enfermedad de Parkinson

Nuestros colegas y amigos del Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System de Seattle,USA, han publicado recientemente este completo y actualizado análisis de los genes vinculados a EP.
J Geriatr Psychiatry Neurol. 2010 Dec;23(4):228-42.

GWAS 2010 asociación EP con HLA

Hamza TH et al, Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease, Nat Genet. 2010 Aug 15. [Epub ahead of print].