Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

View ORCID ProfileFulya Akçimen, Sandra Martins, View ORCID ProfileCalwing Liao, Cynthia V. Bourassa, Hélène Catoire, Garth A. Nicholson, View ORCID ProfileOlaf Riess, View ORCID ProfileMafalda Raposo, Marcondes C. França Jr., João Vasconcelos, Manuela Lima, View ORCID ProfileIscia Lopes-Cendes, View ORCID ProfileMaria Luiza Saraiva-Pereira, Laura B. Jardim, Jorge Sequeiros, Patrick A. Dion, View ORCID ProfileGuy A. Rouleau
doi: https://doi.org/10.1101/834754
Fulya Akçimen
1Department of Human Genetics, McGill University, Montréal, QC, Canada
2Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Fulya Akçimen
Sandra Martins
3i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
4IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Calwing Liao
1Department of Human Genetics, McGill University, Montréal, QC, Canada
2Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Calwing Liao
Cynthia V. Bourassa
2Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada
5Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hélène Catoire
2Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada
5Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Garth A. Nicholson
6University of Sydney, Department of Medicine, Concord Hospital, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olaf Riess
7Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Olaf Riess
Mafalda Raposo
8Faculdade de Ciências e Tecnologia, Universidade dos Açores e Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mafalda Raposo
Marcondes C. França Jr.
9Department of Neurology, Faculty of Medical Sciences, UNICAMP, Campinas, SP, Brazil
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
João Vasconcelos
10School of Medical Sciences, Department of Medical Genetics and Genomic Medicine, University of Campinas (UNICAMP), Campinas, SP, Brazil
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manuela Lima
8Faculdade de Ciências e Tecnologia, Universidade dos Açores e Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iscia Lopes-Cendes
11The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil
12Departamento de Neurologia, Hospital do Divino Espírito Santo, Ponta Delgada, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Iscia Lopes-Cendes
Maria Luiza Saraiva-Pereira
13Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
14Depto. de Bioquímica – ICBS, Universidade Federal do Rio Grande do Sul (UFRGS)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maria Luiza Saraiva-Pereira
Laura B. Jardim
13Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
15Depto de Medicina Interna, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jorge Sequeiros
4IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
16Institute for Molecular and Cell Biology (IBMC), Universidade do Porto, Porto, Portugal
17Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick A. Dion
2Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada
5Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guy A. Rouleau
1Department of Human Genetics, McGill University, Montréal, QC, Canada
2Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada
5Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Guy A. Rouleau
  • For correspondence: guy.rouleau@mcgill.ca
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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. 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 08, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
Fulya Akçimen, Sandra Martins, Calwing Liao, Cynthia V. Bourassa, Hélène Catoire, Garth A. Nicholson, Olaf Riess, Mafalda Raposo, Marcondes C. França Jr., João Vasconcelos, Manuela Lima, Iscia Lopes-Cendes, Maria Luiza Saraiva-Pereira, Laura B. Jardim, Jorge Sequeiros, Patrick A. Dion, Guy A. Rouleau
bioRxiv 834754; doi: https://doi.org/10.1101/834754
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
Fulya Akçimen, Sandra Martins, Calwing Liao, Cynthia V. Bourassa, Hélène Catoire, Garth A. Nicholson, Olaf Riess, Mafalda Raposo, Marcondes C. França Jr., João Vasconcelos, Manuela Lima, Iscia Lopes-Cendes, Maria Luiza Saraiva-Pereira, Laura B. Jardim, Jorge Sequeiros, Patrick A. Dion, Guy A. Rouleau
bioRxiv 834754; doi: https://doi.org/10.1101/834754

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3689)
  • Biochemistry (7797)
  • Bioengineering (5676)
  • Bioinformatics (21290)
  • Biophysics (10578)
  • Cancer Biology (8176)
  • Cell Biology (11945)
  • Clinical Trials (138)
  • Developmental Biology (6763)
  • Ecology (10401)
  • Epidemiology (2065)
  • Evolutionary Biology (13867)
  • Genetics (9708)
  • Genomics (13073)
  • Immunology (8146)
  • Microbiology (20014)
  • Molecular Biology (7853)
  • Neuroscience (43058)
  • Paleontology (320)
  • Pathology (1279)
  • Pharmacology and Toxicology (2258)
  • Physiology (3353)
  • Plant Biology (7232)
  • Scientific Communication and Education (1312)
  • Synthetic Biology (2006)
  • Systems Biology (5538)
  • Zoology (1128)