Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/142510
Author(s): Akçimen, F
Martins, S
Liao, C
Bourassa, CV
Catoire, H
Nicholson, GA
Riess, O
Raposo, M
França, MC
Vasconcelos, J
Lima, M
Lopes-Cendes, I
Saraiva-Pereira, ML
Jardim, LB
Sequeiros, J
Dion, PA
Rouleau, GA
Title: Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
Publisher: Impact Journals
Issue Date: 2020
Abstract: Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study (Pearson's correlation coefficient R2 = 0.62). Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10-5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.
URI: https://hdl.handle.net/10216/142510
Source: Aging, vol.12(6), p. 4742-4756
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: https://creativecommons.org/licenses/by/3.0/
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
10.18632-aging.102825.pdf1.65 MBAdobe PDFThumbnail
View/Open


This item is licensed under a Creative Commons License Creative Commons