Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
PLoS Genet
; 8(12): e1003098, 2012.
Article
em En
| MEDLINE
| ID: mdl-23284291
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 Nâ=â50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMAâ=â)5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMAâ=â)4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMAâ=â)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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fumar
/
Capacidade Vital
/
Volume Expiratório Forçado
/
Doença Pulmonar Obstrutiva Crônica
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos