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
First approach: 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). Second
approach: 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 nonannotated
intergenic regions on chromosomes 9 and 12, that showed suggestive evidence
for interaction with active tobacco smoking in the onset of adult asthma.