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NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
- Source :
- Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Nature genetics, 48(9), 1037-1042. Nature Publishing Group, Nature Genetics, 48(9), 1037–1042. Nature Publishing Group, Nature genetics
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology. ispartof: Nature Genetics vol:48 issue:9 pages:1037-+ ispartof: location:United States status: published
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Genomics
Biology
medicine.disease_cause
Article
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Journal Article
Genetics
medicine
Humans
Comparative Study
Exome
Genetic Predisposition to Disease
SLAGEN Consortium
Risk factor
Amyotrophic lateral sclerosis
Gene
Genetic Association Studies
Netherlands
Mutation
Amyotrophic Lateral Sclerosis
Case-control study
11 Medical And Health Sciences
06 Biological Sciences
medicine.disease
3. Good health
NIMA-Related Kinase 1
030104 developmental biology
RC0346
Case-Control Studies
Medical genetics
Human medicine
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....5ffe85f56c0e2362c392bc0d9f3321b7