Years before diagnosis, quality of life declines for Parkinson's disease patients

Years before diagnosis, quality of life declines for Parkinson's disease patients

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]

Libro Genética de la Enfermedad de Parkinson

Para que llegue a todos los interesados, comparto el libro en Google Drive.

Se puede descargar aquí en (pdf).

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/

Mes de generación de conciencia sobre la Enfermedad de Parkinson

http://spittoon.23andme.com/2012/04/02/parkinsons-awareness-month/

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.

Genética y Enfermedad de Parkinson

Un excelente artículo para entender las bases de la investigación en genética de la EP (en inglés) en la web de la Parkinson´s Disease Foundation:

Genetics: A Foundation for Future Parkinson's Treatments por Matthew Farrer.

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]

JORNADA DE ACTUALIZACIÓN EN ENFERMEDAD DE PARKINSON Y AFECCIONES RELACIONADAS

Viernes 19 de agosto de 2011 - 8:30 - 12:00 horas.

Anfiteatro del Instituto de Neurología.

Hospital de Clínicas, Piso 2.

Programa.

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.