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

TLDR: It is shown 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.

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 12q132, a known autoimmune disease locus, with IP6K2 (P = 58 × 10(-15)), PRIC285 (P = 30 × 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