Correlation between DNA methylation in mononuclear and polymorphonuclear cells.

<p>Comparison of DNA methylation levels measured in two cell fractions, mononuclear cells (MNCs) and polymorphonuclear cells (PMNCs). Percent methylation in PMNCs (y-axis) is plotted against percent methylation in MNCs (x-axis). Each dot represents the two measurements for a single CpG per individual. The Spearman ρ for correlation between measurements in MNCs and PMNCs for each CGI is shown in the legend.</p

Percent DNA methylation in mononuclear and polymorphonuclear cells.

<p>Percent DNA methylation (y-axis) in mononuclear and polymorphonuclear cells (MNCs and PMNCs) per CpG site (x-axis) in four CGIs located in the <i>HHEX</i>, <i>KCNJ11</i>, <i>KCNQ1</i> and <i>PM20D1</i> genes respectively (n = 20 each). Data for each CGI are depicted in a separate boxplot where measurements for MNCs are shown in red and for PMNCs in blue. The dotted lines separating the boxes indicate that at each CpG site a pair of data are being compared (i.e., for MNCs and PMNCs). Significantly (p<0.01) differentially methylated CpG sites (MNCs versus PMNCs DNA methylation) are indicated with an asterisk.</p

Percent DNA methylation in whole blood samples.

<p>Percent DNA methylation (y-axis) in whole blood DNA per CpG site (x-axis) in four CGIs located in the <i>HHEX</i> (n = 169), <i>KCNJ11</i> (n = 54), <i>KCNQ1</i> (n = 49) and <i>PM20D1</i> (n = 59) genes respectively. Data for each CGI are depicted in a separate boxplot. Below each boxplot is a gene-map which roughly indicates the position of the analyzed CpG sites (adapted from the UCSC genome browser) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046705#pone.0046705-Kent1" target="_blank">[12]</a>. Genes are depicted in blue, the exons as blocks, the introns as thin lines connecting the blocks, and the 5′ and 3′ untranslated regions as thin blocks at each end. CGIs are shown as green blocks. The genomic position depicted for each CGI is; 10:94,439,661–94,445,388 (chromosome:first base-last base) for the <i>HHEX</i> CGI, chr11:17,363,372–17,366,783 for the <i>KCNJ11</i> CGI, chr11:2,422,797–2,826,916 for the <i>KCNQ1</i> CGI and chr1:204,063,776–204,085,881 for the <i>PM20D1</i> CGI. The gene map for <i>KCNQ1</i> includes the <i>KCNQ1OT1</i> (<i>KCNQ1</i> overlapping transcript 1) gene, which appears as a large exon roughly in the middle of the map. Arrows indicate the direction of transcription and the position of the transcription start site.</p

Characteristics of individuals included in the study^*.

*<p>Abbreviations; WB:Whole blood (i.e., population studied for DNA methylation in whole blood), BCF: Blood cell fraction (i.e., population studied for DNA methylation in blood cell fractions), NE: Neutrophils, LY: Lymphocytes, MO: Monocytes, EO: Eosinophils, BA: Basophils.</p

Baseline characteristics of study participants by cohort.

<p>Values correspond to N (%) or mean (standard deviation). The standard deviation of each gene score in each cohort is 1 due to the method of standardization used.—AGES, indicates the Age, Gene/Environment Susceptibility—Reykjavik study; ARIC, Atherosclerosis Risk in Communities; FHS, Framingham Heart Study; MDCS, Malmö Diet and Cancer study; RS, Rotterdam Study; WGHS, Women's Genome Health Study; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDLc, high density lipoprotein cholesterol; LDLc, low density lipoprotein cholesterol; LVH, left ventricular hypertrophy; NA, not available, * not fasting.</p

Previously discovered multivariable-adjusted cohort-specific Hazard Ratios and 95% Confidence Intervals of the risk of atrial fibrillation associated with blood lipids.

<p>Associations are per 1 standard deviation increase unless noted. ARIC, Atherosclerosis Risk in Communities; FHS, Framingham Heart Study; WHS, Women's Health Study; MESA, Multi-Ethnic Study of Atherosclerosis; CHS, Cardiovascular Health Study.</p

Multivariable adjusted Hazard Ratios (95% confidence interval) of Atrial Fibrillation of a 1 Standard Deviation Increase in Lipid Gene Score, by Cohort.

<p>HR, Hazard Ratio; CI, Confidence interval; NA, not available. -AGES, indicates the Age, Gene/Environment Susceptibility—Reykjavik study; ARIC, Atherosclerosis Risk in Communities; FHS, Framingham Heart Study; MDCS, Malmö Diet and Cancer study; RS, Rotterdam Study; WGHS, Women's Genome Health Study. Model 1: Cox proportional hazard model adjusted for age, sex and study center, if appropriate. Model 2: Model 1 + education, height, smoking status, body mass index, systolic blood pressure, diastolic blood pressure, use of antihypertensive medication, diabetes, left ventricular hypertrophy, previous stroke, previous coronary heart disease and previous heart failure. Model 3: Model 2 + adjusted for continuous lipid levels and lipid medication use.</p

Association of validated SNPs for BMI (from Speliotes et al, Nature Genetics 2010) [39].

<p>All CT traits presented with the same coded allele, and all are modeled relative to the previously-published BMI trait-increasing allele. Z-statistic indicates direction relative to the coded allele.</p

Association of SNPs from a Recently Published GWAS of Body Fat Distribution^* (Heid IM et al, NG, 2010) [32].

<p>All data modeled relative to the previously-published trait-increasing allele; the z-statistic indicates the effect direction relative to the coded allele.</p>*<p>Measured by WHR-adjusted-for-BMI.</p

The forest plots for β_int of the four most significant interaction terms after meta-analysis of the replication cohorts: rs2315598-rs2853228 (a), rs6848132-rs7863451 (b), rs3756856-rs11758333 (c) and rs4596126-rs11676467 (d).

<p>Although the analysis in the discovery and the filtering was done with scaled phenotypes, for these forest plots, the HDL levels are not scaled in the Rotterdam Study cohorts.</p