ATXN2 trinucleotide repeat length correlates with risk of ALS

6533b821fe1ef96bd127b07b

RESEARCH PRODUCT

ATXN2 trinucleotide repeat length correlates with risk of ALS

Pietro Fratta Aleksey Shatunov Isabelle Le Ber Vincenzo La Bella Owen A. Ross Peter M. Andersen Tim Van Langenhove François Salachas Monica Forzan John Powell Jan H. Veldink Andrea Malaspina Claire Troakes Maria Del Mar Amador Christine Van Broeckhoven Nancy M. Bonini Stéphanie Millecamps Daniel Stahl Cinzia Gellera Aaron D. Gitler John Hardy Vincent Meininger Giovanni Stevanin Katie Sidle Serena Lattante Gianni Sorarù Ben Gaastra Leonard H. Van Den Berg Christopher E. Shaw Philip Van Damme Guy A. Rouleau Safa Al-sarraj Bing-wen Soong Richard W. Orrell Maryam Shoai Yi-chung Lee Isabella Fogh Hussein Daoud Rosa Rademakers Wim Robberecht Ashley R. Jones Wouter Van Rheenen Ammar Al-chalabi Bradley N. Smith Francesca Luisa Conforti Edor Kabashi William Sproviero

subject

Male Expansion 0301 basic medicine Aging ATXN2 gene Settore MED/03 - GENETICA MEDICA 0302 clinical medicine Trinucleotide Repeats Genetic Report Abstract Amyotrophic lateral sclerosis Ataxin-2 Genetics CAG General Neuroscience ATXN2 Triplet 3. Good health Female Psychology Neurovetenskaper Risk Neuroscience(all)Age of onset Clinical Neurology 03 medical and health sciences SCA2 Trinucleotide repeat Journal Article medicine Humans Allele Alleles Genetic Association Studies Amyotrophic lateral sclerosi Intermediate expansion Neuroscience (all)Neurosciences Exponential risk Case-control study Amyotrophic lateral sclerosis medicine.disease Clinical neurology Ageing 030104 developmental biology Case-Control Studies Human medicine Neurology (clinical)ALS Geriatrics and Gerontology Age of onset Trinucleotide Repeat Expansion Trinucleotide repeat expansion ALS; ATXN2; Age of onset; Amyotrophic lateral sclerosis; CAG; Expansion; Exponential risk; Intermediate expansion; Risk; SCA2; Trinucleotide repeat; Triplet Neuroscience 030217 neurology & neurosurgery Meta-Analysis Developmental Biology

description

We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. publisher: Elsevier articletitle: ATXN2 trinucleotide repeat length correlates with risk of ALS journaltitle: Neurobiology of Aging articlelink: http://dx.doi.org/10.1016/j.neurobiolaging.2016.11.010 content_type: article copyright: © 2016 The Author(s). Published by Elsevier Inc. ispartof: Neurobiology of Aging vol:51 pages:178- ispartof: location:United States status: published

year	journal	country	edition	language
2017-03-01	Neurobiology of Aging

https://doi.org/10.1016/j.neurobiolaging.2016.11.010