Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus

Fig. 1. Manhattan Plots and Q-Q Plots for T2D BMI-unadjusted and BMI-adjusted Models. Manhattan plot (A, C) and Q-Q plot (B, D) for BMI-adjusted (A, B) and for BMI-unadjusted (C, D) GWAS. Manhattan plots represent SNPs (dots) plotted on x-axis in accordance with chromosome position against their corresponding -log10(P). The red horizontal line represents the threshold for genome-wide significance (P < 5 × 10− 08). Q-Q plots represent the quantile distribution of observed P values versus the quantile distribution of expected P values for all SNPs

Fig. 2. Comparison of Allele Frequencies and Effect sizes (BETA) of Replicated SNPs Identified in the GWAS Catalog and QBB Cohort. Correlation of allele frequencies for replicated loci between QBB and GWAS catalog; A-B. BMI-unadjusted and C-D. BMI-adjusted models. Blue dots represent SNPs with similar direction of effect size, while red dots represent SNPs with opposite direction of effect size

Fig. 3. Regional Association Plots of Novel Loci showing Genome-wide Significant Association with T2D. The plot shows the chromosomal position of (A) rs143508949 and (B) rs2510095 plotted against -log10P values (based on NCBI human genome build 38). The novel SNP (diamond) and other detected SNPs (circle) are color coded based on LD (square correlation (r2)). (C) The lead SNP rs2510095 is a significant eQTL for DYNC2H1 in Thyroid tissues. Box and whiskers plot shows DYNC2H1expression by rs2510095 genotypes

Fig. 4. The predictive performances and translatability of T2D polygenic risk scoring panels derived from European- and multi-ancestries. The predictive performances of PGS derived from the European ancestry (PGS000036) and multi-ancestry (PGS000804) when applied to participants from QBB cohort and other ancestries was assessed by the area under the receiver operating curves (AUC) values. (A) Bar plots show the predictive performances of the European-ancestry PGS when applied to QBB participants and Europeans [35], and (B) the predictive performances of multi-ancestry PGS when applied to participants from QBB, European, African and Hispanic or Latin American ancestries [32] in the basic model (without covariate adjustment). (C) Bar plots show the predictive performances of the European-ancestry PGS when applied to QBB and European [34] ancestries and (D) the predictive performances of multi-ancestry PGS when applied to participants from QBB, European, African and Hispanic or Latin American ancestries in the full model (with covariate adjustment). Error bars represent 95% confidence interval for AUC. *Predictive performance of the two PGS showed statistical significance (P < 0.05) in all…