Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Cell Rep ; 43(1): 113611, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38159276

RESUMEN

Complement is a fundamental innate immune response component. Its alterations are associated with severe systemic diseases. To illuminate the complement's genetic underpinnings, we conduct genome-wide association studies of the functional activity of the classical (CP), lectin (LP), and alternative (AP) complement pathways in the Cooperative Health Research in South Tyrol study (n = 4,990). We identify seven loci, encompassing 13 independent, pathway-specific variants located in or near complement genes (CFHR4, C7, C2, MBL2) and non-complement genes (PDE3A, TNXB, ABO), explaining up to 74% of complement pathways' genetic heritability and implicating long-range haplotypes associated with LP at MBL2. Two-sample Mendelian randomization analyses, supported by transcriptome- and proteome-wide colocalization, confirm known causal pathways, establish within-complement feedback loops, and implicate causality of ABO on LP and of CFHR2 and C7 on AP. LP causally influences collectin-11 and KAAG1 levels and the risk of mouth ulcers. These results build a comprehensive resource to investigate the role of complement in human health.


Asunto(s)
Estudio de Asociación del Genoma Completo , Lectina de Unión a Manosa , Humanos , Activación de Complemento , Proteínas del Sistema Complemento/metabolismo , Lectinas/metabolismo , Haplotipos/genética , Lectina de Unión a Manosa/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...