Pleiotropic genetic architecture and novel loci for C-reactive protein levels.
Nat Commun
; 13(1): 6939, 2022 11 14.
Article
em En
| MEDLINE
| ID: mdl-36376304
ABSTRACT
C-reactive protein is involved in a plethora of pathophysiological conditions. Many genetic loci associated with C-reactive protein are annotated to lipid and glucose metabolism genes supporting common biological pathways between inflammation and metabolic traits. To identify novel pleiotropic loci, we perform multi-trait analysis of genome-wide association studies on C-reactive protein levels along with cardiometabolic traits, followed by a series of in silico analyses including colocalization, phenome-wide association studies and Mendelian randomization. We find 41 novel loci and 19 gene sets associated with C-reactive protein with various pleiotropic effects. Additionally, 41 variants colocalize between C-reactive protein and cardiometabolic risk factors and 12 of them display unexpected discordant effects between the shared traits which are translated into discordant associations with clinical outcomes in subsequent phenome-wide association studies. Our findings provide insights into shared mechanisms underlying inflammation and lipid metabolism, representing potential preventive and therapeutic targets.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína C-Reativa
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Grécia