Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

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 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

Posttraumatic rupture of interventricular septum

Cardiac rupture is a extremely acute condition, and it often results in fatality. Main causes of heart rupture are myocardial infarctions, traumas and infections. Recently we have observed increases post-traumatic heart diseases. Timely diagnostics substantially influences management of the patient and potential for survival. And the echocardiography is a reliable, noninvasive and high-informative method in early diagnosis of this pathology. We present a case of the post-traumatic interventricular septum rupture diagnosed by echocardiography and the subsequent xenopericardial patch repair

Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium

International audienceBackground 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 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

Forest plots for the meta-analysis and replication study on the genetic effect of SNP rs9969775 on chromosome 9 in subjects exposed and non-exposed to ever active tobacco smoking (identified in first approach).

<p>The bottom forest plot presents the interaction meta-analysis and replication study for this SNP. ORs are calculated using a fixed effect model.</p

Top SNPs that interact with active tobacco smoking in adult onset asthma identified in first approach (overall interaction effect)^#.

<p>Top SNPs that interact with active tobacco smoking in adult onset asthma identified in first approach (overall interaction effect)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172716#t002fn001" target="_blank">^#</a>.</p

PRISMA flow diagram.

<p>PRISMA flow diagram.</p

Top SNPs that interact with active tobacco smoking in adult onset asthma identified in second approach (genetic effect in exposed)^#.

<p>Top SNPs that interact with active tobacco smoking in adult onset asthma identified in second approach (genetic effect in exposed)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172716#t003fn001" target="_blank">^#</a>.</p

Top SNPs that interact with active tobacco smoking in adult onset asthma identified in both approaches^#.

<p>Top SNPs that interact with active tobacco smoking in adult onset asthma identified in both approaches<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172716#t004fn001" target="_blank">^#</a>.</p

Study populations included in GWI study on active smoking and adult onset asthma.

<p>Study populations included in GWI study on active smoking and adult onset asthma.</p

Forest plots for the meta-analysis and replication study on the genetic effect of SNP rs5011804 on chromosome 12 in subjects exposed and non-exposed to ever active tobacco smoking (identified in second approach).

<p>The bottom forest plot presents the interaction meta-analysis and replication study for this SNP. ORs are calculated using a fixed effect model.</p