Journal article
Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset
Scientific Reports, Vol.12(1), Art. 14739
2022
Abstract
Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico short structural variant (SSV) evaluation algorithm and investigated in two cohorts of North American sALS patients, both separately and combined (Duke cohort n = 138, Coriell cohort n = 333; combined cohort n = 471), compared to a group of healthy controls from the Coriell Institute biobank (n = 496). Stratification according to site of disease onset revealed that the 9 TTTA allele was associated with reduced disease risk, specifically confined to spinal-onset sALS patients in the Duke cohort (p = 0.001). Furthermore, carriage of the 10 TTTA allele was associated with a 2.7 year later age of disease onset in the larger combined sALS cohort (p = 0.02). These results suggest that the 9 and 10 TTTA motif length may have a protective advantage for potentially lowering the risk of sALS and delaying the age of disease onset, however, these results need to be replicated in larger multicenter and multi-ethnic cohorts.
Details
- Title
- Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset
- Authors/Creators
- F. Theunissen (Author/Creator) - Perron Institute for Neurological and Translational ScienceR.S. Anderton (Author/Creator)F.L. Mastaglia (Author/Creator)I. James (Author/Creator)R. Bedlack (Author/Creator)P.A. Akkari (Author/Creator)
- Publication Details
- Scientific Reports, Vol.12(1), Art. 14739
- Publisher
- Springer Nature
- Identifiers
- 991005545512107891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics; Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.765 ALS Mechanisms
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Neuroscience & Behavior