Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.
PLoS One
; 12(3): e0172716, 2017.
Article
en En
| MEDLINE
| ID: mdl-28253294
ABSTRACT
BACKGROUND:
Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma.METHODS:
We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects.RESULTS:
Firstapproach:
50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis:
ORint = 0.50, p = 7.63*10-5, replication ORint = 0.65, p = 0.02). Secondapproach:
35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication ORint = 1.40, p = 0.03).CONCLUSIONS:
Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Asma
/
Fumar
/
Estudio de Asociación del Genoma Completo
/
Interacción Gen-Ambiente
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Límite:
Adult
/
Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Países Bajos