The Impact of Complement Genes on the Risk of Late-Onset Alzheimer's Disease.
Genes (Basel)
; 12(3)2021 03 20.
Article
em En
| MEDLINE
| ID: mdl-33804666
ABSTRACT
Late-onset Alzheimer's disease (LOAD), the most common cause of dementia, and a huge global health challenge, is a neurodegenerative disease of uncertain aetiology. To deliver effective diagnostics and therapeutics, understanding the molecular basis of the disease is essential. Contemporary large genome-wide association studies (GWAS) have identified over seventy novel genetic susceptibility loci for LOAD. Most are implicated in microglial or inflammatory pathways, bringing inflammation to the fore as a candidate pathological pathway. Among the most significant GWAS hits are three complement genes CLU, encoding the fluid-phase complement inhibitor clusterin; CR1 encoding complement receptor 1 (CR1); and recently, C1S encoding the complement enzyme C1s. Complement activation is a critical driver of inflammation; changes in complement genes may impact risk by altering the inflammatory status in the brain. To assess complement gene association with LOAD risk, we manually created a comprehensive complement gene list and tested these in gene-set analysis with LOAD summary statistics. We confirmed associations of CLU and CR1 genes with LOAD but showed no significant associations for the complement gene-set when excluding CLU and CR1. No significant association with other complement genes, including C1S, was seen in the IGAP dataset; however, these may emerge from larger datasets.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complemento C1s
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Receptores de Complemento 3b
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Clusterina
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Doença de Alzheimer
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido