Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis.pdf (774.93 kB)
Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis
journal contribution
posted on 2023-06-09, 04:37 authored by Benjamin Gaastra, Aleksey Shatunov, Sara Pulit, Ashley Jones, William Sproviero, Alexandra Gillett, Zhongbo Chen, Janine Kirby, Isabella Fogh, John F Powell, Nigel LeighNigel Leigh, Karen Morrison, Pamela J Shaw, Christopher E Shaw, Leonard H van den Berg, Jan H Veldink, Cathryn M Lewis, Ammar Al-ChalabiOur 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.
History
Publication status
- Published
File Version
- Published version
Journal
Amyotrophic Lateral Sclerosis and Frontotemporal DegenerationISSN
2167-8421Publisher
Taylor & FrancisExternal DOI
Issue
7-8Volume
17Page range
593-599Department affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-01-11First Open Access (FOA) Date
2017-01-11First Compliant Deposit (FCD) Date
2017-01-11Usage metrics
Categories
No categories selectedLicence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC