title: Identification of STOML2 as a putative novel asthma risk gene associated with IL6R.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Revez
authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Matheson
authors.affiliation: PathWest Laboratory Medicine of Western Australia (WA), Nedlands, WA, Australia.|School of Population Health, The University of WA, Nedlands, WA, Australia.|School of Pathology and Laboratory Medicine, The University of WA, Nedlands, WA, Australia.|Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Hui
authors.affiliation: Institute for Respiratory Health, University of WA, Perth, WA, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Baltic
authors.affiliation: Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.|School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.|Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, WA, Australia.
authors.forename: A
authors.initials: A
authors.lastname: James
authors.affiliation: School of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Qld, Australia.
authors.forename: J W
authors.initials: JW
authors.lastname: Upham
authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: S
authors.initials: S
authors.lastname: Dharmage
authors.affiliation: Institute for Respiratory Health, University of WA, Perth, WA, Australia.|School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
authors.forename: J L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.
authors.forename: M A R
authors.initials: MA
authors.lastname: Ferreira
mesh_terms: D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; D019947:Receptors, Interleukin-6; C406287:STOML2 protein, human
keywords: IL-6; IL-6R; SLP2; allergy; mitochondria