Forest plot for meta-analysis on the association between ever active tobacco smoking and adult onset asthma, without including the genetic effect.

<p>Forest plot for meta-analysis on the association between ever active tobacco smoking and adult onset asthma, without including the genetic effect.</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

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

Genetic effect of SNP rs5011804 following an additive model in the LifeLines cohort (N = 12,475), stratified by different tobacco smoke exposures.

<p>Genetic effect of SNP rs5011804 following an additive model in the LifeLines cohort (N = 12,475), stratified by different tobacco smoke exposures.</p

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets