Clinical characteristics of the study samples at time of DNA collection^α.

α<p>Data are means ± standard deviations or percentages;</p>β<p>Age here refers to the age when the DNA samples.</p

Kaplan-Meier survival function for rs4149313 and survival of MI in STR (A) and ULSAM (B).

<p>Survival function of MI for individuals having no (A/A; blue line); one (A/G; red line) or two (G/G; green line) risk alleles at <i>ABCA1</i> rs4149313 locus.</p

Forest plot for independent replication of association between rs4149313 and CAD in CARDIoGRAMplusC4D.

<p>Fixed-effect meta-analysis was applied for effect of rs4149313 on CAD in CARDIoGRAMplusC4D consortium. The diamond in the bottom represents the confidence interval of this independent replication.</p

Region plot of the <i>ABCA1</i> locus (chromosome 9 co-ordinates 106157871–107157392) in the Swedish Twin Registry.

<p>The SNP rs4149313 with the strongest association is marked by a bright blue diamond. Each rhomb represents a SNP and the brightness represents the extent of linkage disequilibrium with the lead SNP. The recombination rates are marked with yellow lines. Relevant genes and genomic coordinates are shown below the plots. Plots were generated using SNAP (<a href="http://www.broadinstitute.org/mpg/snap/ldplot.php" target="_blank">http://www.broadinstitute.org/mpg/snap/ldplot.php</a>. Accessed 2013 Mar 1.) and based on HapMap CEU release 22, NCBI B36 assembly, dbSNP build 126.</p

Associations of genetic loci with MI in primary and replication analyses.

α<p>Only SNPs associated with MI with a nominal P<0.01 in STR are presented. Data are hazard ratios with 95% confidence intervals and P-values from Cox proportional hazards regression models using age as time scale and study entry at age 18, adjusting for sex. The effect allele was defined as the minor allele in our study.</p>β<p>Proxies rs2236513, rs4759275, and rs8066560 were used instead of lead SNPs rs3183702, rs11172106 and rs9899634, respectively in ULSAM (r² = 1, 0.84 and 1) in all the results from the replication study.</p>γ<p>CELSR2 and SORT1 reside in a cluster consisting of CELSR2/PSRC1/SORT1; APOA4 resides in a cluster of apolipoproteins APOA5/APOA4/APOC3/APOA1.</p>δ<p>rs5090 was not successfully genotyped in ULSAM.</p>ε<p>Alleles are presented as effect/other alleles.</p><p>Abbreviations: SNP, single nucleotide polymorphism; HR, hazard ratio; CI, confidence interval.</p

SNPs showing significant associations with different IMT measurements.

<p>Chr: chromosome, A1: coded allele, P: p-value for association with IMT, CC-IMT_mean: average IMT of the common carotid in a segment excluding the first cm proximal to the bifurcation, CC-IMT_max: maximum IMT of the common carotid in a segment excluding the first cm proximal to the bifurcation, ICA-IMT_mean: average IMT of the internal carotid, ICA-IMT_max: maximum IMT of the internal carotid, Bif-IMT_mean: average IMT of the bifurcation, Bif-IMT_max: maximum IMT of the bifurcation, IMT_mean: average IMT composite value considering the whole carotid tree derived from the segment-specific measurements, IMT_max: Maximum IMT measure considering the whole carotid tree derived from the segment-specific measurements, IMT_mean-max: average of the IMT_max values for the whole carotid tree derived from the segment-specific measurements. rs4888378 was used as proxy SNP for rs2865531.</p

Information of the 26 lung function-associated SNPs selected in the present study [13], [14], [15], [16].

<p>Columns 1 to 9 refer to frequencies, beta and p values for the association of SNPs with lung function fenotypes as found in the literature. Columns 10 to 15 refer to the frequencies and total sample sizes of the same or proxy-SNPs that were looked up in IMPROVE.</p><p>SNP ID: rs number for the SNPs selected from literature. Chr: chromosome, A1: coded allele, A1 freq: frequency of the coded allele, Measure reported: phenotype for which the SNP reached genome-wide significant association, SE: standard error, P: p-value for association with measure reported, proxy LD: linkage disequilibrium between SNP ID from literature (column 1) and the proxy used for replication in IMPROVE (column 11), proxy SNP: rs number for the proxy SNPs used for replication in IMPROVE, n: number of individuals tested in IMPROVE.</p

String-database network connections between proximal cis-gene and target plasma protein.

<p>All short String paths that connect proximal cis-genes with the target plasma protein are shown. The colour intensity of each gene shows the eQTL association-strength with the index-SNP. The nodes highlighted with bold border show paths that satisfy P<0.05 in network permutation analysis. A) the rs61598054-SNP is harboured in an intron of the <i>LACE1</i> gene, but have no paths to the target gene <i>NGF</i> and a more likely mechanism is therefore <i>FOXO3</i> -> <i>AKT1</i> -> <i>NGF</i>, which involves a rs61598054-trans-eQTL effect on <i>AKT1</i>. In permutation analysis of re-wired networks this is stronger than 95% of random networks. B) Similarly for rs693918, while located between <i>SRD5A2</i> and <i>MEMO1</i>, the path <i>XDH</i> -> <i>TLR4</i> -> <i>IL18</i> is a more likely mechanistic path, supported by eQTL effects on both <i>XDH</i> and <i>TLR4</i>. C) The rs61598054-<i>AKT1</i> trans-eQTL from panel A in 235 IFN-stimulated monocytes and the rs10947260-ATF3 trans-eQTL from panel D in 89 mammary artery samples. D) Example of ambiguous findings regarding the rs10947260 -> -> -> IL6: The SNP has a coding-proxy in <i>BTNL2</i>, literature mining evidence for the <i>AGER</i> gene, but also eQTL-weighted pathway evidence for both <i>ATF6B</i> and <i>NOTCH4</i>.</p

Systematic analysis of potential mechanisms behind trans-pQTL associations.

<p>Systematic analysis of potential mechanisms behind trans-pQTL associations.</p

Association between pQTLs and Coronary Artery Disease (CAD) risk.

<p>Each SNP from supplemental <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006706#pgen.1006706.s003" target="_blank">S1 Table</a> was investigated in the CARDIoGRAMplusC4D data, and the P-values for the pQTL and CAD risk were extracted. An additional pooled analysis was performed in cases where one plasma protein had multiple pQTLs,. The table shows all pQTLs for which either a single-SNP or pooled CAD association had a P<0.05. P-values highlighted in italics indicate that the association was also significant after FDR correction for multiple testing.</p