Identifying disease-critical cell types and cellular processes by integrating single-cell RNA-sequencing and human genetics.
Nat Genet
; 54(10): 1479-1492, 2022 10.
Article
en En
| MEDLINE
| ID: mdl-36175791
ABSTRACT
Genome-wide association studies provide a powerful means of identifying loci and genes contributing to disease, but in many cases, the related cell types/states through which genes confer disease risk remain unknown. Deciphering such relationships is important for identifying pathogenic processes and developing therapeutics. In the present study, we introduce sc-linker, a framework for integrating single-cell RNA-sequencing, epigenomic SNP-to-gene maps and genome-wide association study summary statistics to infer the underlying cell types and processes by which genetic variants influence disease. The inferred disease enrichments recapitulated known biology and highlighted notable cell-disease relationships, including γ-aminobutyric acid-ergic neurons in major depressive disorder, a disease-dependent M-cell program in ulcerative colitis and a disease-specific complement cascade process in multiple sclerosis. In autoimmune disease, both healthy and disease-dependent immune cell-type programs were associated, whereas only disease-dependent epithelial cell programs were prominent, suggesting a role in disease response rather than initiation. Our framework provides a powerful approach for identifying the cell types and cellular processes by which genetic variants influence disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastorno Depresivo Mayor
/
Estudio de Asociación del Genoma Completo
Límite:
Humans
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos