Identification of STOML2 as a putative novel asthma risk gene associated with IL6R

Background Functional variants in the interleukin‐6 receptor gene (IL6R) are associated with asthma risk. We hypothesized that genes co‐expressed with IL6R might also be regulated by genetic polymorphisms that are associated with asthma risk. The aim of this study was to identify such genes. Methods...

Full description

Saved in:
Bibliographic Details
Published in:Allergy (Copenhagen) 2016-07, Vol.71 (7), p.1020-1030
Main Authors: Revez, J. A., Matheson, M. C., Hui, J., Baltic, S., James, A., Upham, J. W., Dharmage, S., Thompson, P. J., Martin, N. G., Hopper, J. L., Ferreira, M. A. R.
Format: Article
Language:English
Subjects:
Alleles
allergy
Asthma
Asthma - genetics
Asthma - metabolism
Blood Proteins - genetics
Cell Line
Chromosome Mapping
Cluster Analysis
Computational Biology - methods
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Genetic Association Studies
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
IL‐6
IL‐6R
Membrane Proteins - genetics
mitochondria
Polymorphism, Single Nucleotide
Receptors, Interleukin-6 - genetics
Receptors, Interleukin-6 - metabolism
Risk factors
Signal Transduction
SLP2
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Functional variants in the interleukin‐6 receptor gene (IL6R) are associated with asthma risk. We hypothesized that genes co‐expressed with IL6R might also be regulated by genetic polymorphisms that are associated with asthma risk. The aim of this study was to identify such genes. Methods To identify genes whose expression was correlated with that of IL6R, we analyzed gene expression levels generated for 373 human lymphoblastoid cell lines by the Geuvadis consortium and for 38 hematopoietic cell types by the Differentiation Map Portal (DMAP) project. Genes correlated with IL6R were then screened for nearby single nucleotide polymorphisms (SNPs) that were significantly associated with both variation in gene expression levels (eSNPs) and asthma risk. Results We identified 90 genes with expression levels correlated with those of IL6R and that also had a nearby eSNP associated with disease risk in a published asthma GWAS (N = 20 776). For 16 (18%) genes, the association between the eSNP and asthma risk replicated with the same direction of effect in a further independent published asthma GWAS (N = 27 378). Among the top replicated associations (FDR < 0.05) were eSNPs for four known (IL18R1, IL18RAP, BCL6, and STAT6) and one putative novel asthma risk gene, stomatin‐like protein 2 (STOML2). The expression of STOML2 was negatively correlated with IL6R, while eSNPs that increased the expression of STOML2 were associated with an increased asthma risk. Conclusion The expression of STOML2, a gene that plays a key role in mitochondrial function and T‐cell activation, is associated with both IL‐6 signaling and asthma risk.
ISSN:0105-4538
1398-9995
DOI:10.1111/all.12869