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Nat Genet. 2012 Mar 25;44(5):502-10. doi: 10.1038/ng.2205.

Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.

Author information

  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. bfairfax@well.ox.ac.uk

Abstract

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.

Comment in

PMID:
22446964
[PubMed - indexed for MEDLINE]
PMCID:
PMC3437404
Free PMC Article

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