Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth.
PLoS Genet
; 16(11): e1009163, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-33227023
ABSTRACT
Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10-9), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Citocinas
/
Sitios de Carácter Cuantitativo
/
Inflamación
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
/
Newborn
País/Región como asunto:
Europa
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Dinamarca