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Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis

Gaastra, B; Shatunov, A; Pulit, S; Jones, AR; Sproviero, W; Gillett, A; Chen, Z; ... Al-Chalabi, A; + view all (2016) Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration , 17 (7-8) pp. 593-599. 10.1080/21678421.2016.1213852. Green open access

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Abstract

Our objective was to identify whether rare genetic variation in amyotrophic lateral sclerosis (ALS) candidate survival genes modifies ALS survival. Candidate genes were selected based on evidence for modifying ALS survival. Each tail of the extreme 1.5% of survival was selected from the UK MND DNA Bank and all samples available underwent whole genome sequencing. A replication set from the Netherlands was used for validation. Sequences of candidate survival genes were extracted and variants passing quality control with a minor allele frequency ≤0.05 were selected for association testing. Analysis was by burden testing using SKAT. Candidate survival genes UNC13A, KIFAP3, and EPHA4 were tested for association in a UK sample comprising 25 short survivors and 25 long survivors. Results showed that only SNVs in UNC13A were associated with survival (p = 6.57 × 10-3). SNV rs10419420:G > A was found exclusively in long survivors (3/25) and rs4808092:G > A exclusively in short survivors (4/25). These findings were not replicated in a Dutch sample. In conclusion, population specific rare variants of UNC13A may modulate survival in ALS.

Type: Article
Title: Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/21678421.2016.1213852
Publisher version: https://doi.org/10.1080/21678421.2016.1213852
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: ALS, UNC13A, genetic modifiers, sequencing, survival, Adaptor Proteins, Signal Transducing, Amyotrophic Lateral Sclerosis, Cohort Studies, Cytoskeletal Proteins, Databases, Bibliographic, Female, Genotype, Humans, Male, Middle Aged, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Receptor, EphA4, Survival Analysis, Time Factors, United Kingdom
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10058761
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