PMID- 22446964
OWN - NLM
STAT- MEDLINE
DCOM- 20120702
LR  - 20220129
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 44
IP  - 5
DP  - 2012 Mar 25
TI  - Genetics of gene expression in primary immune cells identifies cell type-specific 
      master regulators and roles of HLA alleles.
PG  - 502-10
LID - 10.1038/ng.2205 [doi]
AB  - 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 (PPARgamma) 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.
FAU - Fairfax, Benjamin P
AU  - Fairfax BP
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. 
      bfairfax@well.ox.ac.uk
FAU - Makino, Seiko
AU  - Makino S
FAU - Radhakrishnan, Jayachandran
AU  - Radhakrishnan J
FAU - Plant, Katharine
AU  - Plant K
FAU - Leslie, Stephen
AU  - Leslie S
FAU - Dilthey, Alexander
AU  - Dilthey A
FAU - Ellis, Peter
AU  - Ellis P
FAU - Langford, Cordelia
AU  - Langford C
FAU - Vannberg, Fredrik O
AU  - Vannberg FO
FAU - Knight, Julian C
AU  - Knight JC
LA  - eng
GR  - 281824/ERC_/European Research Council/International
GR  - 075491/Z/04/WT_/Wellcome Trust/United Kingdom
GR  - 439/DH_/Department of Health/United Kingdom
GR  - 074318/Wellcome Trust/United Kingdom
GR  - 090532/Wellcome Trust/United Kingdom
GR  - 088891/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120325
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Genetic Markers)
RN  - 0 (HLA Antigens)
RN  - 0 (KLF4 protein, human)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (PPAR gamma)
SB  - IM
CIN - Nat Genet. 2012 May;44(5):478-80. PMID: 22538719
MH  - Alleles
MH  - Autoimmune Diseases/etiology
MH  - B-Lymphocytes/immunology/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Genetic Markers/*genetics
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/genetics
MH  - Monocytes/immunology/*metabolism
MH  - PPAR gamma/genetics
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Quantitative Trait Loci/*genetics
PMC - PMC3437404
MID - UKMS40993
OID - NLM: UKMS40993
EDAT- 2012/03/27 06:00
MHDA- 2012/07/03 06:00
PMCR- 2012/11/01
CRDT- 2012/03/27 06:00
PHST- 2011/10/07 00:00 [received]
PHST- 2012/01/31 00:00 [accepted]
PHST- 2012/03/27 06:00 [entrez]
PHST- 2012/03/27 06:00 [pubmed]
PHST- 2012/07/03 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - ng.2205 [pii]
AID - 10.1038/ng.2205 [doi]
PST - epublish
SO  - Nat Genet. 2012 Mar 25;44(5):502-10. doi: 10.1038/ng.2205.