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

被引：377

作者：

Fairfax, Benjamin P. ^{[1
]}

Makino, Seiko ^{[1
]}

Radhakrishnan, Jayachandran ^{[1
]}

Plant, Katharine ^{[1
]}

Leslie, Stephen ^{[2
]}

Dilthey, Alexander ^{[3
]}

Ellis, Peter ^{[4
]}

Langford, Cordelia ^{[4
]}

Vannberg, Fredrik O. ^{[1
,5
]}

Knight, Julian C. ^{[1
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[2] Univ Oxford, Dept Oncol, Oxford, England

[3] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[4] Univ Cambridge, Wellcome Trust Sanger Inst, Cambridge, England

[5] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 05期

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; DETERMINANTS; PSORIASIS; SNP; VISUALIZATION; APOPTOSIS; COMPLEX;

D O I：

10.1038/ng.2205

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-15)), PRIC285 (P = 3.0 x 10(-10)) and an upstream region of CDKN1A (P = 2 x 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor gamma (PPAR gamma) 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.

引用

页码：502 / +

页数：10

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