Genome-Wide association study of quantitative biomarkers identifies a novel locus for alzheimer's disease at 12p12.1.
BMC Genomics
; 23(1): 85, 2022 Jan 28.
Article
em En
| MEDLINE
| ID: mdl-35086473
ABSTRACT
BACKGROUND:
Genetic study of quantitative biomarkers in Alzheimer's Disease (AD) is a promising method to identify novel genetic factors and relevant endophenotypes, which provides valuable information to deconvolute mechanistic complexity and better understand disease subtypes.RESULTS:
Using the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we performed a genome-wide association study (GWAS) between 565,373 single nucleotide polymorphisms (SNPs) and 16 key AD biomarkers from 1,576 subjects at four visits. We identified a novel locus rs5011804 at 12p12.1 significantly associated with several AD biomarkers, including three cognitive traits (CDRSB, FAQ, ADAS13) and one imaging trait (fusiform volume). Additional mediation and interaction analyses investigated the relationships among this SNP, relevant biomarkers, and clinical diagnosis, confirming and further elaborating the genetic effects seen in the GWAS.CONCLUSION:
Our GWAS not only affirms key AD genes but also suggests the promising role of the SNP rs5011804 due to its associations with several AD cognitive and imaging outcomes. The SNP rs5011804 has a reported association with adult asthma and slightly affects intracranial volume but has not been associated with AD before. Our novel findings contribute to a more comprehensive view of the molecular mechanism behind AD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article