PMID- 20844574
OWN - NLM
STAT- MEDLINE
DCOM- 20110104
LR  - 20211020
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 6
IP  - 9
DP  - 2010 Sep 9
TI  - An immune response network associated with blood lipid levels.
PG  - e1001113
LID - e1001113 [pii]
LID - 10.1371/journal.pgen.1001113 [doi]
AB  - While recent scans for genetic variation associated with human disease have been 
      immensely successful in uncovering large numbers of loci, far fewer studies have 
      focused on the underlying pathways of disease pathogenesis. Many loci which are 
      associated with disease and complex phenotypes map to non-coding, regulatory 
      regions of the genome, indicating that modulation of gene transcription plays a 
      key role. Thus, this study generated genome-wide profiles of both genetic and 
      transcriptional variation from the total blood extracts of over 500 
      randomly-selected, unrelated individuals. Using measurements of blood lipids, key 
      players in the progression of atherosclerosis, three levels of biological 
      information are integrated in order to investigate the interactions between 
      circulating leukocytes and proximal lipid compounds. Pair-wise correlations 
      between gene expression and lipid concentration indicate a prominent role for 
      basophil granulocytes and mast cells, cell types central to powerful allergic and 
      inflammatory responses. Network analysis of gene co-expression showed that the 
      top associations function as part of a single, previously unknown gene module, 
      the Lipid Leukocyte (LL) module. This module replicated in T cells from an 
      independent cohort while also displaying potential tissue specificity. Further, 
      genetic variation driving LL module expression included the single nucleotide 
      polymorphism (SNP) most strongly associated with serum immunoglobulin E (IgE) 
      levels, a key antibody in allergy. Structural Equation Modeling (SEM) indicated 
      that LL module is at least partially reactive to blood lipid levels. Taken 
      together, this study uncovers a gene network linking blood lipids and circulating 
      cell types and offers insight into the hypothesis that the inflammatory response 
      plays a prominent role in metabolism and the potential control of atherogenesis.
FAU - Inouye, Michael
AU  - Inouye M
AD  - Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust 
      Genome Campus, Hinxton, United Kingdom. inouye@wehi.edu.au
FAU - Silander, Kaisa
AU  - Silander K
FAU - Hamalainen, Eija
AU  - Hamalainen E
FAU - Salomaa, Veikko
AU  - Salomaa V
FAU - Harald, Kennet
AU  - Harald K
FAU - Jousilahti, Pekka
AU  - Jousilahti P
FAU - Mannisto, Satu
AU  - Mannisto S
FAU - Eriksson, Johan G
AU  - Eriksson JG
FAU - Saarela, Janna
AU  - Saarela J
FAU - Ripatti, Samuli
AU  - Ripatti S
FAU - Perola, Markus
AU  - Perola M
FAU - van Ommen, Gert-Jan B
AU  - van Ommen GJ
FAU - Taskinen, Marja-Riitta
AU  - Taskinen MR
FAU - Palotie, Aarno
AU  - Palotie A
FAU - Dermitzakis, Emmanouil T
AU  - Dermitzakis ET
FAU - Peltonen, Leena
AU  - Peltonen L
LA  - eng
GR  - WT089061/Wellcome Trust/United Kingdom
GR  - WT089062/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100909
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (Apolipoproteins B)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipids)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apolipoproteins B/blood
MH  - Cohort Studies
MH  - Gene Expression Regulation
MH  - Gene Regulatory Networks/*genetics
MH  - Genetic Variation
MH  - Humans
MH  - Hypersensitivity/blood/genetics/immunology
MH  - Immunity/*genetics
MH  - Inflammation Mediators/blood
MH  - Leukocytes/metabolism
MH  - Lipids/*blood
MH  - Lipoproteins, HDL/blood
MH  - Metabolic Syndrome/blood/genetics
MH  - Middle Aged
MH  - Models, Genetic
MH  - Obesity/blood/genetics
MH  - Quantitative Trait Loci/genetics
MH  - Regression Analysis
MH  - Triglycerides/blood
PMC - PMC2936545
COIS- The authors have declared that no competing interests exist.
EDAT- 2010/09/17 06:00
MHDA- 2011/01/05 06:00
PMCR- 2010/09/01
CRDT- 2010/09/17 06:00
PHST- 2010/04/08 00:00 [received]
PHST- 2010/08/05 00:00 [accepted]
PHST- 2010/09/17 06:00 [entrez]
PHST- 2010/09/17 06:00 [pubmed]
PHST- 2011/01/05 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - e1001113 [pii]
AID - 10-PLGE-RA-NV-2976R2 [pii]
AID - 10.1371/journal.pgen.1001113 [doi]
PST - epublish
SO  - PLoS Genet. 2010 Sep 9;6(9):e1001113. doi: 10.1371/journal.pgen.1001113.