Difference in leukocyte telomere length between ultra-marathon runners and controls.

<p>The differences are expressed as unstandardized β-coefficients with standard errors from either stepwise linear regression (Fully adjusted model 1) or linear regression (Fully adjusted model 2– Forced), MAP – mean arterial pressure, IL-6– interleukin-6, PCR Plate – experiment used in measurement in LTL, BMI – body mass index, TC – total cholesterol, HDL-C – high-density lipoprotein cholesterol, CRP – C-reactive protein, sICAM – soluble intercellular adhesion molecule-1.</p

Pearson's linear correlation between age and leukocyte telomere length in ultra-marathon runners and controls.

<p>Ultra-marathon runners are indicated by filled circles and controls are indicated by empty circles.</p

Clinical phenotypes of ultra-marathon runners and apparently healthy controls.

<p>Data are from either Student’s t-test or Mann-Whitney U-tests and are expressed as means and standard deviations or geometric means and 95% confidence intervals (*); BMI – body mass index, MAP – mean arterial pressure, TC – total cholesterol, HDL – high-density lipoprotein cholesterol, CRP – C-reactive protein, IL-6– interleukin-6, sICAM-1– soluble intercellular.</p

Summary of subjects, methods and analyses.

<p>a. Number of SNP pairs for which interaction testing was performed - may not equal the number of possible pair-wise tests [n*(n−1)/2] because some pairs were captured in previous Analyses (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041730#pone.0041730.s001" target="_blank">File S1</a> Supporting <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041730#pone-0041730-g002" target="_blank">Figure 2</a>), and some tests were not feasible due to low allele frequencies (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041730#pone.0041730.s001" target="_blank">File S1</a> Section 3.3). b. Significance threshold computed using permutations under the null hypothesis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041730#pone.0041730.s001" target="_blank">File S1</a> Section 3.4) c. SNP pairs with p-value for interaction within 3 orders of magnitude of the significance threshold for each Analysis were brought forward for validation in the WTCCC sample; the numbers of SNP pairs for which data were available in the WTCCC study are shown. <i>LDL</i>, concentration of LDL cholesterol; <i>HDL</i>, concentration of HDL cholesterol; <i>TG</i>, triglyceride concentration; <i>BP</i>, blood pressure; <i>CH</i>, carbohydrate metabolism (loci associated with risk of Type II diabetes and related phenotypes, such as fasting glucose concentration); <i>SMK</i>, smoking; <i>OB</i>, obesity; <i>small LDL</i>, concentration of small atherogenic LDL particles; <i>Lp(a)</i>, plasma levels of lipoprotein(a); <i>CHD</i>, risk of coronary heart disease; <i>MI</i>, risk of myocardial infarction.</p

Results of gene-gene interaction search among CVRF SNPs (Analysis 1).

<p><i>Panel A</i>. Plot of the top result (arrow) from Analysis 1 against the distribution of the top results from 10,000 permutations under the null hypothesis (dotted line). The permuted top results are expected to follow a beta-distribution (solid line, parameters obtained from permuted top results), the 95^th percentile of which was taken as the significance level required to obtain a Type II error of 0.05 (arrow). <i>Inset</i>: While the significance level computed in Analysis 1 (dashed black line) was estimated using 10,000 null permutations, this estimate was found to stabilize rapidly with increasing number of permutations (black points) and to change little after 100–200 permutations. Consequently, we progressively reduced the number of permutations used to estimate the significance level in subsequent Analyses. <i>Panel B</i>. Quantile-quantile plot showing rank-ordered observed results (black points) from 29,161 tests in Analysis 1 (<i>y-axis</i>) against expected results (<i>x-axis</i>) estimated from 10,000 permutations under the null hypothesis (randomized phenotype). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041730#pone.0041730.s001" target="_blank">File S1</a> Section 3.5 for computation methods. The shaded area corresponds to the 95%CI of the permuted expected results. The 95%CI of a normal distribution is indicated by the dotted lines. <i>Panel C</i>. Estimation of the interaction effect sizes this analysis has 80% power to detect across a range of MAF under an additive × additive interaction model. The heights of the vertical bars correspond to the effect size (OR) detectable for a typical pair of SNPs whose MAFs are as indicated on the horizontal axes.</p

Suggestive SNP-SNP interactions—primary analysis.

<p>SNP: single nucleotide polymorphism, Chr: chromosome; MAF: minor allele frequency; BHF-FHS: British Heart Foundation Family Heart Study; MIGen: Myocardial Infarction Genetics Consortium; SNPA Pvalue: level of nominal statistical significance for single marker association with coronary artery disease for SNP A; SNPB Pvalue: level of nominal statistical significance for single marker association with coronary artery disease for SNP B; Int. Pvalue BHF-FHS: interaction P value in BHF-FHS; Int. Pvalue MIGen: interaction P value in MIGen; N/A: replication not available. PDE11A: phosphodiesterase 11A; SEC1P: secretory blood group 1, pseudogene; SERPINA12: serpin peptidase inhibitor, clade A; SRI: sorcin; ZHX2: zinc fingers and homeoboxes 2; NR5A2: nuclear receptor subfamily 5, group A, member 2; ANGPTL4: angiopoietin-like 4; NRG3: neuregulin 3; RPSAP15: ribosomal protein SA pseudogene 15; CSRP3: cysteine and glycine-rich protein 3; GSTM3: glutathione S-transferase mu 3; RYR2: ryanodine receptor 2; TBXAS1: thromboxane A synthase 1; TAC1: tachykinin, precursor 1; P2RX4: purinergic receptor P2X, ligand-gated ion channel, 4; SCARB2: scavenger receptor class B, member 2; NOD1: nucleotide-binding oligomerization domain containing 1; PDGFD: platelet derived growth factor D.</p><p>Suggestive SNP-SNP interactions—primary analysis.</p

Baseline Characteristics of cases in the British Heart Foundation-Family Heart Study and the Myocardial Infarction Genetics studies.

<p>Data are means and standard deviations or counts and percentages, BHF-FHS: British Heart Foundation Family Heart Study; MIGen: Myocardial Infarction Genetics Consortium; MI: myocardial infarction; BMI: body mass index.</p><p>Baseline Characteristics of cases in the British Heart Foundation-Family Heart Study and the Myocardial Infarction Genetics studies.</p

A schematic illustration of SNP selection process for the primary analysis.

<p>A schematic illustration of SNP selection process for the primary analysis.</p

SNP selection process for the secondary analysis.

<p>SNP selection process for the secondary analysis.</p

Changes in obesity measures and lipids between 2004 and 2006 in the cross-sectional and prospective LIPIDOGRAM Studies.

<p>Data are changes between 2004 and 2006 are expressed as β-coefficients with standard errors (SE); BMI – body mass index; HDL-C – high-density lipoprotein cholesterol; TG – triglycerides; TC – total cholesterol; LDL-C – low-density lipoprotein cholesterol; Basic – unadjusted model; Full – model adjusted for age, age², sex, region of recruitment, height, education and smoking.</p