Heatmap single gene/multiple phenotype.

<p>This figure shows the 22 most important association rules as columns in a heatmap. Note that only one member of the <i>UGT1A</i> family is listed and rules for the same gene are summarized in the same column.</p

Multiple gene/single phenotype association table.

<p>This table shows multiple gene/single phenotype association values. The first column is the phenotype, the second column is the CCA association value, the third column is Fisher's combined association value and the fourth column are the genes associated. In parentheses the single gene/single phenotype association value is given for each gene.</p><p>Multiple gene/single phenotype association table.</p

Single gene/single phenotype association.

<p>This table shows single phenotype/single genotype association gene-centered association value. The first column represents genes, the second column phenotypes, the third column represents the CCA association value and the fourth column is the Pubmed ID if the association has been previously reported.</p><p>Single gene/single phenotype association.</p

Multiple gene/multiple phenotype association table.

<p>This table shows multiple gene/multiple phenotypes association rules. The first column are the multiple genes, the second column the CCA association value and the third column the multiple phenotypes.</p><p>Multiple gene/multiple phenotype association table.</p

Single gene/multiple phenotype association.

<p>This table shows single gene/multiple phenotype association. The first column represents the gene, the second column represents the CCA association value, the third column is the Fisher's combined association value and the fourth column the phenotypes associated. In parentheses is the single phenotype association value of each phenotype.</p><p>Single gene/multiple phenotype association.</p

Hive plot for single gene/single phenotype.

<p>The vertical axis represents the association value (higher, more association). The left axis represents phenotypes and the right axis represents genes. An interactive hive plot is published on the project webpage (<a href="http://pleioexp.epi.bris.ac.uk/cca/1gene1phenhive.html" target="_blank">http://pleioexp.epi.bris.ac.uk/cca/1gene1phenhive.html</a>).</p

Prevalence of COPD adjusted for age and stratified by smoking status.

<p>Prevalence of COPD adjusted for age and stratified by smoking status.</p

Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies

<div><p>Background</p><p>The association of <i>APOE</i> genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention.</p><p>Methods and Findings</p><p>To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, <i>p <</i> 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both <i>p <</i> 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both <i>p <</i> 0.001), high-density lipoprotein (correlation coefficient 0.16 and −0.14, respectively; both <i>p <</i> 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both <i>p <</i> 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, <i>p =</i> 0.001) and lipoprotein(a) (correlation coefficient −0.11, <i>p <</i> 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect.</p><p>Conclusions</p><p>In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of <i>APOE</i> genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE.</p></div

Baseline characteristics of studies included.

<p>Baseline characteristics of studies included.</p

Cross-sectional association between geometric mean of ApoE concentration and C-reactive protein measured in ELSA, by gender.

<p>Male (circles) and female (square) mean log ApoE concentration was calculated for each decile of the associated variable and plotted to visualise the shape of the association. Bars give 95% CIs.</p