Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort.
Neurobiol Aging
; 74: 234.e9-234.e15, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-30342764
ABSTRACT
NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Expansión de las Repeticiones de ADN
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Estudios de Asociación Genética
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Esclerosis Amiotrófica Lateral
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Proteínas de la Membrana
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Aging
Año:
2019
Tipo del documento:
Article
País de afiliación:
Países Bajos