Regional plots for novel lipid loci with array-wide significant regions in IBC meta-analysis of African ancestry.

<p><b>A.. </b><i>CD36</i> region, <b>B.. </b><i>ICAM1</i> region. Loci are shown as the lead SNP with a flanking region depicting the candidate gene and nearby genes included on the array. The purple diamond represents the lead SNP in the IBC meta-analysis and the dots represent the surrounding SNPs, with the different colors showing the LD relationship with the lead SNP based on YRI HapMap II information. −log10 p-values for association with HDL-C (for <i>CD36</i>) and TC (for <i>ICAM1</i>) are shown for each SNP (left-hand axis). Recombination rates in YRI HapMap II is shown in blue traces (right-hand axis).</p

Replication results of nine signals in 7,000 African Americans.

<p>RAF risk allele frequency, SE standard error.</p

Schematic design of study for the multi-ethnic IBC-Lipid association meta-analysis.

<p>The workflow includes primary analyses and secondary analyses. Details can be found in the text.</p

Loci with significant evidence of independent lipid association signals.

<p>Chr chromosome, BP base pair, RAF risk allele frequency, SE standard error.</p

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

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

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

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

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