Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease.
Science
; 376(6589): eabf3041, 2022 04 08.
Article
em En
| MEDLINE
| ID: mdl-35389779
ABSTRACT
The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Leucócitos Mononucleares
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália