mRNA expression of <i>ZC3H11B, SLC30A10</i>, and <i>LYPLAL1</i> in human tissues.

<p>Expression of mRNA for the three genes was examined in human brain, placenta, neural retina (retina), retinal pigment epithelium (RPE) and sclera from adult tissues, and retina/RPE and sclera from 24-week gestation fetal tissues using reverse transcription polymerase chain reaction (RT-PCR). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a housekeeping gene and was used as an internal control for the quantification of mRNA expression. NTC (No template control) served as a negative control with the use of water rather than cDNA during PCR.</p

Top SNPs (<i>P_meta</i>-value≤1×10⁻⁵) associated with AL from the meta-analysis in the three Asian cohorts.

a<p>MA, minor allele.</p>b<p>MAF, minor allele frequency in each cohort.</p>c<p>GWAS cohorts. SCES - Singapore Chinese Eye Study; SCORM - Singapore Cohort study of the Risk factors for Myopia; SiMES - Singapore Malay Eye Study.</p>d<p>β, coefficient of linear regression; s.e., standard error for coefficient β. Association between each genetic marker and AL was examined using linear regression, adjusted for age, gender, height and level of education. The effect sizes denote changes in millimeter of AL per each additional copy of the minor allele.</p>e<p><i>P_het</i>, <i>P</i>-value for heterogeneity by Cochran's Q test across three study cohorts.</p

Transcription quantification of <i>ZC3H11A</i>, <i>SLC30A10</i>, and <i>LYPLAL1</i> in mouse retina, retinal pigment epithelium, and sclera in induced myopic eyes, fellow eyes, and independent control eyes.

<p>Myopia was induced using −15 diopter negative lenses in the right eye of mice for 6 weeks. Uncovered left eyes were served as fellow eyes and age-matched naive mice eyes were controls. Quantification of mRNA expression in mice neural retina (retina), retinal pigment epithelium (RPE) and sclera using quantitative real-time PCR. The bar represents the fold changes of mRNA for each gene after normalization using <i>GAPDH</i> as reference. The mRNA levels of murine <i>ZC3H11A</i>, a gene that is conserved with respect to <i>ZC3H11B</i> in human, <i>SLC30A10</i> and <i>LYPLAL1</i> in myopic and fellow retina, RPE and sclera are compared with independent controls with <i>P</i>-values as follows: <i>ZC3H11A</i> (retina/RPE/sclera, <i>P</i> = 2.60×10⁻⁵, 2.62×10⁻⁶ and 1.08×10⁻⁴ respectively), <i>SLC30A10</i> (<i>P</i> = 2.00×10⁻⁴, 2.00×10⁻⁴ and 4.02×10⁻⁴ respectively) and <i>LYPLAL1</i> (<i>P</i> = 1.50×10⁻⁴, 1.50×10⁻⁴, 1.54×10⁻⁴ respectively). *P<0.0001.</p

The chromosome 1q41 region and its association with axial length in the Asian cohorts.

<p>A) Regional plots for AL from the meta-analysis of three Asian GWAS cohorts: SCES, SCORM and SiMES. The association signals in a 1 megabase (Mb) region at chromosome 1q41 from 217,400 kb to 218,400 kb around the top SNP rs4373767 (red diamond) are plotted. The degree of pair-wise LD between the rs4373767 and any genotyped SNPs in this region is indicated by red shading, measured by r². Superimposed on the plots are gene locations and recombination rates in HapMap Chinese and Japanese populations (blue lines). B) LD plot showing pair-wise r² for all the SNPs genotyped in HapMap database residing between rs4428898 and rs7544369, inclusively, at chromosome 1q41. The four identified top SNPs are in red rectangles. The LD plot is generated by Haploview using SNPs (MAF>1%) genotyped on Han Chinese and Japanese samples in the HapMap database. All coordinates are in Build hg18.</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, 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

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