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

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

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

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