A Genome-Wide Association Study of α-Synuclein Levels in Cerebrospinal Fluid.
Neurotox Res
; 35(1): 41-48, 2019 Jan.
Article
en En
| MEDLINE
| ID: mdl-29959729
ABSTRACT
α-Synuclein is a 140-amino acid protein produced predominantly by neurons in the brain which plays a role in the regulation of neurotransmitter release, synaptic function, and plasticity, thus making it the focus in understanding the etiology of a group of neurodegenerative diseases. We conducted genome-wide association studies (GWAS) of α-synuclein levels in cerebrospinal fluid (CSF) with 209 non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort using a linear regression model to identify novel variants associated with α-synuclein concentration. The minor allele (T) of rs7072338 in the long intergenic non-protein coding RNA 1515 (LINC01515) and the minor allele (T) of rs17794023 in clusterin-associated protein 1 (CLUAP1) were associated with higher CSF α-synuclein levels at genome-wide significance (P = 4.167 × 10-9 and 9.56 × 10-9, respectively). In addition, single nucleotide polymorphisms (SNPs) near amyloid beta precursor protein (APP) (rs1394839) (P = 2.31 × 10-7), Rap guanine nucleotide exchange factor 1 (RAPGEF1) (rs10901091) (P = 8.07 × 10-7), and two intergenic loci on chromosome 2 and 14 (rs11687064 P = 2.50 × 10-7and rs7147386 P = 4.05 × 10-7) were identified as suggestive loci associated with CSF α-synuclein levels. We have identified significantly associated SNPs for CSF α-synuclein. These associations have important implications for a better understanding of α-synuclein regulation and allow researchers to further explore the relationships between these SNPs and α-synuclein-related neurodegenerative disorders.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Precursor de Proteína beta-Amiloide
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Factor 2 Liberador de Guanina Nucleótido
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Alfa-Sinucleína
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ARN Largo no Codificante
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Antígenos de Neoplasias
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
Límite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurotox Res
Asunto de la revista:
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China