DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Pulmonary function (interaction). The EFO term forced expiratory volume was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: forced expiratory volume

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

DB Hancock, M Soler Artigas, SA Gharib, A Henry, A Manichaikul, A Ramasamy, DW Loth, M Imboden, B Koch, WL McArdle, AV Smith, J Smolonska, A Sood, W Tang, JB Wilk, G Zhai, JH Zhao, H Aschard, KM Burkart, I Curjuric, M Eijgelsheim, P Elliott, X Gu, TB Harris, C Janson, G Homuth, PG Hysi, JZ Liu, LR Loehr, K Lohman, RJ Loos, AK Manning, KD Marciante, M Obeidat, DS Postma, MC Aldrich, GG Brusselle, TH Chen, G Eiriksdottir, N Franceschini, J Heinrich, JI Rotter, C Wijmenga, OD Williams, AR Bentley, A Hofman, CC Laurie, T Lumley, AC Morrison, BR Joubert, F Rivadeneira, DJ Couper, SB Kritchevsky, Y Liu, M Wjst, LV Wain, JM Vonk, AG Uitterlinden, T Rochat, SS Rich, BM Psaty, GT O'Connor, KE North, DB Mirel, B Meibohm, LJ Launer, KT Khaw, AL Hartikainen, CJ Hammond, S Gläser, J Marchini, P Kraft, NJ Wareham, H Völzke, BH Stricker, TD Spector, NM Probst-Hensch, D Jarvis, MR Jarvelin, SR Heckbert, V Gudnason, HM Boezen, RG Barr, PA Cassano, DP Strachan, M Fornage, IP Hall, J Dupuis, MD Tobin, SJ London

TITLE:

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

JOURNAL:

PLoS genetics None 2012, Vol 8, pp. e1003098

ABSTRACT:

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects. PUBMED: 23284291
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