Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.
Nat Genet
; 44(5): 502-10, 2012 Mar 25.
Article
en En
| MEDLINE
| ID: mdl-22446964
Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10(-15)), PRIC285 (P = 3.0 × 10(-10)) and an upstream region of CDKN1A (P = 2 × 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Monocitos
/
Marcadores Genéticos
/
Predisposición Genética a la Enfermedad
/
Polimorfismo de Nucleótido Simple
/
Sitios de Carácter Cuantitativo
/
Antígenos HLA
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2012
Tipo del documento:
Article
Pais de publicación:
Estados Unidos