Identified Biomarkers for the Risk of Developing Type 2 Diabetes.

<p>The length of bars denotes total number of incident type 2 diabetes cases across all studies for each biomarker.</p

Flow Diagram of Studies Identified in the Literature Search for the Identification of Biomarkers for T2D.

<p>Flow Diagram of Studies Identified in the Literature Search for the Identification of Biomarkers for T2D.</p

Mendelian randomization estimates of the association of systolic blood pressure with AD in individual ADGC studies and overall in ADGC, GERAD1, and IGAP.

<p>This figure shows MR estimates for the association of SBP-associated variants with AD in each of the participant studies in ADGC [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001841#pmed.1001841.ref024" target="_blank">24</a>] and in GERAD1 [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001841#pmed.1001841.ref025" target="_blank">25</a>] using individual SNP-level data compared to that observed in IGAP [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001841#pmed.1001841.ref012" target="_blank">12</a>] using summary-level data. See <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001841#pmed.1001841.s015" target="_blank">S1 Text</a> (supplemental results) for individual study name abbreviations.</p

Association of the systolic blood pressure genetic score with systolic blood pressure by age stratum in the EPIC-InterAct subcohort.

<p>This figure shows the association between the genetic score for SBP and SBP in the EPIC-InterAct study by age stratum [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001841#pmed.1001841.ref026" target="_blank">26</a>]. Analyses were adjusted for sex, center of recruitment, and subcohort status.</p

Associations of the systolic blood pressure genetic score with binary outcomes in the EPIC-InterAct study.

<p>This figure shows the investigation of pleiotropic associations of the genetic score for SBP with binary outcomes in the EPIC-InterAct study [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001841#pmed.1001841.ref026" target="_blank">26</a>]. The OR per SBP-raising allele is shown.</p

Design of the study.

<p>DIAGRAM, DIAbetes Genetics Replication And Meta-analysis.</p

Genetically predicted or measured levels of the branched-chain amino acids and risk of type 2 diabetes.

<p>(A) Comparison of (i) the association of a difference of 1 SD in the levels of BCAAs at baseline with incident type 2 diabetes in prospective observational studies (bars with blue circles) and (ii) the association of a genetically predicted difference of 1 SD in BCAA levels with type 2 diabetes in genetic Mendelian randomisation studies (bars with red squares for analyses of independent genetic variants and bars with orange diamonds for analyses of correlated genetic variants). (B) Regional association plots for the association of variants at the <i>PPM1K</i> locus with valine (top; representative of the three BCAAs) and type 2 diabetes (bottom). Associations were characterised by a peak of signal upstream of the <i>PPM1K</i> gene, with the lead rs1440581 polymorphism and other polymorphisms in high linkage disequilibrium, as well as a peripheral signal overlaying the gene, with variants in lower linkage disequilibrium with the lead polymorphism. (C) Scatter plot of the association of the isoleucine-raising alleles included in the isoleucine genetic score with amino acid levels and with type 2 diabetes risk. (D) The association of the quartiles of isoleucine level at baseline with incident type 2 diabetes in the EPIC-Norfolk case-cohort study, the Framingham Offspring Study, and the Malmö Diet and Cancer Study (1,025 cases of incident type 2 diabetes and 1,182 controls). Error bars represent the 95% confidence intervals around the central estimates. BCAA, branched-chain amino acid; OR, odds ratio; RR, relative risk; SD, standard deviation; T2D, type 2 diabetes.</p