Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways.
Nat Commun
; 14(1): 2743, 2023 05 12.
Article
em En
| MEDLINE
| ID: mdl-37173304
ABSTRACT
Genome-wide association studies (GWAS) have mapped thousands of susceptibility loci associated with immune-mediated diseases. To assess the extent of the genetic sharing across nine immune-mediated diseases we apply genomic structural equation modelling to GWAS data from European populations. We identify three disease groups gastrointestinal tract diseases, rheumatic and systemic diseases, and allergic diseases. Although loci associated with the disease groups are highly specific, they converge on perturbing the same pathways. Finally, we test for colocalization between loci and single-cell eQTLs derived from peripheral blood mononuclear cells. We identify the causal route by which 46 loci predispose to three disease groups and find evidence for eight genes being candidates for drug repurposing. Taken together, here we show that different constellations of diseases have distinct patterns of genetic associations, but that associated loci converge on perturbing different nodes in T cell activation and signalling pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
/
Doenças do Sistema Imunitário
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália