Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
28 Jan 2022
28 Jan 2022
Historique:
received:
15
12
2020
accepted:
21
10
2021
entrez:
29
1
2022
pubmed:
30
1
2022
medline:
30
1
2022
Statut:
epublish
Résumé
There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.
Identifiants
pubmed: 35091648
doi: 10.1038/s41525-021-00267-9
pii: 10.1038/s41525-021-00267-9
pmc: PMC8799638
doi:
Types de publication
Journal Article
Langues
eng
Pagination
8Subventions
Organisme : Medical Research Council
ID : MR/L501529/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R56 NS073873
Pays : United States
Organisme : Motor Neurone Disease Association
ID : SHAW/APR18/864-791
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS073873
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17214
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : MCLAUGHLIN/OCT15/957-799
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100695
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : ALCHALABI-DOBSON/APR14/829-791
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0500289
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300329
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : SHAW/NOV14/985-797
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900688
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L021803/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900635
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : SMITH/APR16/847-791
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17115
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : ALCHALABI-TALBOT/APR14/926-794
Pays : United Kingdom
Organisme : Alzheimer's Society
ID : 171
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600974
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R024804/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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