MOESM1 of Evaluation of pleiotropic effects among common genetic loci identified for cardio-metabolic traits in a Korean population

Additional file 1: Figure S1. The direction of the allelic effect for each of three pleiotropic SNPs in the 12q24.12 region. Figure S2. Protein-protein interactions among three genes in the 12q24.12 region. Table S1. Frequency distribution of minor allele frequencies in Exome chip data. Table S2. Descriptive information of study subjects. Table S3. Replication results of known lipid-associated loci in Korean individuals. Table S4. Population diversity of three pleiotropic SNPs in the 12q24.12 region. Table S5. Evaluation of pleiotropic effect of 12q24.12 (ALDH2, rs671) genotypes. Table S6. Protein-protein interactions among three genes in 12q24.12 region.

Additional file 2: of On the association analysis of CNV data: a fast and robust family-based association method

Simulated data with 2000 replicates for different values of β under WSC, when there are three copy number clusters. (ZIP 138685 kb

Additional file 1: of On the association analysis of CNV data: a fast and robust family-based association method

A complete report for all experiments performed for this work. Text 1. Rao’s score test statistic with the expected copy number. Text 2. Rao’s score test statistic with the probe intensity measurements. Figure S1. Results of the clustering analysis with family samples (A) and cohort samples (B). Figure S2. Schematic representation of the strategy for the CNV analysis. Figure S3. Validation results. Figure S4. Validation results of replication samples by TaqMan qPCR experiment. Table S1. Specification of parameters for the signal model used in the simulation studies. Table S2. Primer information for CNV validation. Table S3. Accuracy of copy number clusters identified with PedCNV. Table S4. Accuracy of copy number clusters identified with CNVtools. Table S5. Accuracy of copy number estimated with silhouette score. Table S6. Empirical type 1 error estimates when M = 6. Table S7. Empirical power estimates when M = 6. Table S8. Empirical power estimates of T 1 and T 1 * which use the expected copy number and the most probable copy number respectively. Table S9. Estimated parameters of T 1 and T 1 * which use the expected copy number and the most probable copy number respectively. (PDF 814 kb

T2D prediction, glycemic genetic score.

<p>Forest plot of association between glycemic genetic score with incident T2D over a decade-long follow-up period, by ancestry. MESA (European and Asian ancestry) and the <i>G6PD</i> variant (rs1050828) in ARIC (European and African American) were not included in the discovery GWAS analysis. Effect estimates were combined in a fixed effects meta-analysis. Overall effect estimate: 1.05, 95% CI 1.04–1.06, <i>p</i> = 2.5 × 10⁻²⁹. ARIC, Atherosclerosis Risk in Communities Study; ES, Effect Size; FHS, Framingham Heart Study; GWAS, genome-wide association study; G6PD, glucose-6-phosphate dehydrogenase; I-Squared, Higgin's I-squared statistic, a measure of heterogeneity; MESA, Multiethnic Study of Atherosclerosis; SCHS, Singapore Chinese Health Study; T2D, type 2 diabetes.</p

Manhattan plot of HbA1c associated variants.

<p>Manhattan plot of the transethnic meta-analysis results in MANTRA. The dashed grey line indicates log₁₀BF = 6. Grey and green points denote known/novel loci, respectively. The lead HbA1c-associated variants identified through the ancestry-specific/transethnic analyses are circled in purple (the <i>G6PD</i> variant was not included in the MANTRA analysis, but the locus on the X-chromosome is indicated in the figure). Lines joining the plot & SNP number denote known loci (black), novel loci (green), and loci with a secondary distinct signal (red). MANTRA, Meta-Analysis of Transethnic Association.</p

Table of HbA1c associated variants.

<p>Table with results and classification of the 60 HbA1c-associated variants. SNP number corresponds to number in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002383#pmed.1002383.g001" target="_blank">Fig 1</a>.</p

T2D prediction, erythrocytic genetic score adjusted for HbA1c as a binary variable.

<p>Forest plot of association between erythrocytic genetic score with incident T2D over a decade-long follow-up period adjusted for HbA1c as a binary variable (≥5.7% versus <5.7%), by ancestry. HbA1c at baseline was not available in SCHS and was excluded from the meta-analysis. MESA (European and Asian ancestry) and the <i>G6PD</i> variant (rs1050828) in ARIC (European and African American) were not included in the discovery GWAS analysis. Effect estimates were combined in a fixed effects meta-analysis. Overall effect estimate: 0.95, 95% CI 0.94–0.96, <i>p</i> = 3.3 × 10⁻¹⁶. ARIC, Atherosclerosis Risk in Communities Study; ES, Effect Size; GWAS, genome-wide association study; FHS, Framingham Heart Study; G6PD, glucose-6-phosphate dehydrogenase; HbA1c, glycated hemoglobin; I-Squared, Higgin's I-squared statistic, a measure of heterogeneity; MESA, multiethnic study of atherosclerosis; SCHS, Singapore Chinese Health Study; T2D, type 2 diabetes.</p

Reclassification of individuals with discordant T2D status based on prevailing diagnostic thresholds for FG and HbA1c before and after accounting for the effect of erythrocytic variants.

<p>Reclassification of individuals with discordant T2D status based on prevailing diagnostic thresholds for FG and HbA1c before and after accounting for the effect of erythrocytic variants.</p

Mean HbA1c of individuals at the bottom 5% and top 5% of the distribution of ancestry-specific genetic scores and rs1050828 by genotype.

<p>The difference in measured HbA1c of individuals at the bottom 5% and top 5% of the distribution of an ancestry-specific additive GS composed of all 60 variants (GS-Total), and the equivalent calculation for an ancestry-specific GS composed of up to 20 erythrocytic variants (GS-E). Far right of the figure shows the mean HbA1c by genotype for chromosome X rs1050828. AA men, African American men; AA women, African American women; HbA1c, glycated hemoglobin; GS, genetic scores.</p

T2D prediction, erythrocytic genetic score.

<p>Forest plot of association between erythrocytic genetic score with incident T2D over a decade-long follow-up period, by ancestry. MESA (European and Asian ancestry) and the <i>G6PD</i> variant (rs1050828) in ARIC (European and African American) were not included in the discovery GWAS analysis. Effect estimates were combined in a fixed effects meta-analysis. Overall effect estimate: 1.00, 95% CI 0.99–1.01, <i>p</i> = 0.60. ARIC, Atherosclerosis Risk in Communities Study; ES, Effect Size, FHS, Framingham Heart Study; GWAS, genome-wide association study; G6PD, glucose-6-phosphate dehydrogenase; I-Squared, Higgin's I-squared statistic, a measure of heterogeneity; MESA, Multiethnic Study of Atherosclerosis; SCHS, Singapore Chinese Health Study; T2D, type 2 diabetes.</p