Genome-wide Network-assisted Association and Enrichment Study of Amyloid Imaging Phenotype in Alzheimer's Disease.
Curr Alzheimer Res
; 16(13): 1163-1174, 2019.
Article
em En
| MEDLINE
| ID: mdl-31755389
ABSTRACT
BACKGROUND:
The etiology of Alzheimer's disease remains poorly understood at the mechanistic level, and genome-wide network-based genetics have the potential to provide new insights into the disease mechanisms.OBJECTIVE:
The study aimed to explore the collective effects of multiple genetic association signals on an AV-45 PET measure, which is a well-known Alzheimer's disease biomarker, by employing a network assisted strategy.METHODS:
First, we took advantage of a dense module search algorithm to identify modules enriched by genetic association signals in a protein-protein interaction network. Next, we performed statistical evaluation to the modules identified by dense module search, including a normalization process to adjust the topological bias in the network, a replication test to ensure the modules were not found randomly , and a permutation test to evaluate unbiased associations between the modules and amyloid imaging phenotype. Finally, topological analysis, module similarity tests and functional enrichment analysis were performed for the identified modules.RESULTS:
We identified 24 consensus modules enriched by robust genetic signals in a genome-wide association analysis. The results not only validated several previously reported AD genes (APOE, APP, TOMM40, DDAH1, PARK2, ATP5C1, PVRL2, ELAVL1, ACTN1 and NRF1), but also nominated a few novel genes (ABL1, ABLIM2) that have not been studied in Alzheimer's disease but have shown associations with other neurodegenerative diseases.CONCLUSION:
The identified genes, consensus modules and enriched pathways may provide important clues to future research on the neurobiology of Alzheimer's disease and suggest potential therapeutic targets.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Tomografia por Emissão de Pósitrons
/
Doença de Alzheimer
/
Amiloide
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Curr Alzheimer Res
Ano de publicação:
2019
Tipo de documento:
Article