Comparison of baseline characteristics of the EAS population used in genetic risk prediction models and full study population.

<p>Comparison of baseline characteristics of the EAS population used in genetic risk prediction models and full study population.</p

Incidence, Discrimination, and Calibration Estimates of Models Using Conventional Risk Factors^* and GWAS or Regression Tree SNPs in the EAS.

*<p>Conventional risk factors = Age, Sex, SBP, Total Cholesterol/HDL Cholesterol, Diabetes and/or glucose intolerance, Smoking.</p><p>Each analysis used only subjects without a diagnosis at baseline, as appropriate to investigate incident events, and with full genotypic data for included SNPs.</p

SNPs identified from meta-analysis of GWAS of CHD used in risk prediction models.

<p>SNPs identified from meta-analysis of GWAS of CHD used in risk prediction models.</p

Functional consequences of variants in the <i>SERPINA6/A1</i> locus significantly associated with morning plasma cortisol in GWAMA, and of the Leuven variant, in CROATIA-Korcula.

a<p>Data for total cortisol is from the whole Croatia-Korcula sample, n = 898.</p>b<p>Samples selected for measured free cortisol assay were age and sex matched homozygotes at rs12589136.</p>c<p>adjusted for age, sex, and first three principal components, using kinship matrix derived from GWAS data.</p><p>Data are geometric mean (95% CI)[n]. Cortisol values are nmol/L, CBG µmol/L, cortisol binding activity nmol/L, and α1-antitrypsin g/L. RCL = reactive centre loop.</p

Forest plot of association of morning plasma cortisol with rs12589136.

<p>Plot shows association as beta values with 95%CI for morning plasma cortisol z-scores for rs12589136 (T allele) in discovery cohorts (blue) and meta-analysis (red).</p

Association with morning plasma cortisol of SNPs representing signals in the <i>SERPINA6/SERPINA1</i> region from meta-analyses of discovery genome-wide association studies and of replication studies.

a<p>adjusted for age and sex.</p>b<p>rs2749527 was replaced with rs2749529 (r² = 0.905, D' = 1.0) as rs2749527 failed manufacture for replication. LD patterns (from SNAP HapMap CEU build 22): rs11621961-rs12589136 (r² = 0.131), rs11621961-rs2749529 (r² = 0.260), rs12589136-rs2749529 (r² = 0.291), rs11621961-rs2749527 (r² = 0.255). Independent SNPs were defined by PLINK using the clumping function (within 500kb, LD r² >0.2, P-value <5x10⁻⁵)</p

Meta-analysis of genome wide association studies for morning plasma cortisol.

<p>A) Manhattan plot of −lop₁₀<i>P</i> values by chromosome. The red horizontal line indicates genome-wide significance (<i>P</i><5×10⁻⁸) and the blue horizontal line indicates moderate significance (<i>P</i><5×10⁻⁵). The lead SNP rs12589136 (chr14:94,793,686; b37) in red is genome-wide significant. SNPs within ±50 kb of cortisol-related candidate genes (listed in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004474#pgen.1004474.s006" target="_blank">Table S6</a>) are highlighted in colours. B) Quantile-quantile plot of −log₁₀<i>P</i>, comparing the distribution of observed −log₁₀<i>P</i>-values and that expected by chance.</p

Regional associations surrounding lead SNP rs12589136 in genome-wide meta-analysis of morning plasma cortisol.

<p>Regional plot shows −log₁₀<i>P</i> values of all SNPs, and degree of correlation between all SNPs and lead SNP rs12589136. SNPs with lower <i>P</i> values span <i>SERPINA6</i> and <i>SERPINA1</i> genes within a recombination boundary.</p

Genome-wide scan for sex-specific genome-wide association highlights numerous loci.

<p>(a) Manhattan plot showing the men-specific (upward, up to 60,586 men) and women-specific (downward, up to 73,137 women) association P-values from the discovery with the 619 selected loci colored by the phenotype for which the locus was selected; (b) QQ-plot showing the sex-specific association P-values as observed against those expected under the null overall phenotypes (black) and for each phenotypes separately (colored).</p

Seven SNPs show sex difference.

a<p>Trait and sex for which the SNP was selected;</p>b<p>Gene labels state the nearest gene or the gene as published previously; details on all genes near the association signal can be found in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500.s002" target="_blank">Figure S2</a>;</p>c<p>One-sided P-Values.</p>d<p>larger sample size due to one additional study that did not have hip circumference, and therefore could not contribute to WHRadjBMI.</p>e<p>smaller sample size as this SNP was not on Metabochip.</p><p>Shown are the seven SNPs with significant (at 5% false discovery rate) sex difference in the follow-up data. These seven SNPs exhibit genome-wide significant association in women (joint discovery and follow-up <i>P_women</i><5×10−8) and only two of these show nominally significant association in men (joint <i>P_men</i><0.05). The three loci MAP3K1, HSD17B4, and PPARG are shown here for the first time for their anthropometric trait association as well as for sex-difference.</p