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]

Un test para Enfermedad de Parkinson en una llamada de teléfono

TED: Max Little: A test for Parkinson’s with a phone call.

En los países como Uruguay, donde tenemos un sistema de salud remotamente parecido a algo adecuado y accesible, la utilidad es menor y lo que el conferencista dice no es igualmente aplicable. Además, los beneficios de ir a un neurólogo van mucho más allá del diagnóstico y el tratamiento. Aquí un post sobre el tema, no centrado en la Neurología sino en la Medicina en general. 

De todos modos el sistema es muy interesante y una innovación potencialmente útil.

via: Nacho F. Mata: @nachogenePD

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.