Correction: Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets

Due to errors in production, Figure 2 and Figure 4 are incorrect. The correct versions are provided here.

Figure 2. Depiction and distance analysis of associations between genotype and DNA methylation of significant mQTLs in human pancreatic islets.

Depiction of (A) the most significant cis-mQTL; rs1771445 vs. cg02372404, and (B) the least significant cis-mQTL; rs196489 vs. cg06433283, among all identified cis-mQTLs in human pancreatic islets. Data is presented as Box and Whisker plots with P-values adjusted for multiple testing. (C) Distance analysis between SNPs and CpG sites of significant cis-mQTLs plotted as the number of identified mQTLs within each distance bin. Distance summary: minimum  =  0 kb, 10%ile  =  1.88 kb, 25%ile  =  7.62 kb, 50%ile  =  26.31 kb, 75%ile  =  74.76 kb, 90%ile  =  164.5 kb, maximum  =  499.6 kb. (D) The strength of associations plotted against the distance between SNPs and CpG sites of significant cis-mQTLs after correction for multiple testing. Depiction of (E) the most significant trans-mQTL; rs17660464 vs. cg22968622, and (F) the least significant trans-mQTL; rs6440971 vs. cg10438649, among all identified trans-mQTLs in human pancreatic islets. Data is presented as Box and Whisker plots with P-values adjusted for multiple testing. (G) Quantile-Quantile plots (Q-Q plots) of –log10 (P-values) illustrating the distribution of P-values for all analyzed SNP-CpG pairs in the cis- (red dots) and trans- (blue dots) mQTL analysis in relation to a theoretical null distribution (grey diagonal line). Bold dots indicate significant mQTLs identified in the cis- (red dots) and trans-(blue dots) mQTL analysis after correction for multiple testing.

Figure 4. CIT analysis identifies mQTLs where DNA methylation potentially mediates genetic associations with mRNA expression in human pancreatic islets.

(A) Depiction of possible relationship models between genotype as a causal factor (G), DNA methylation as a potential mediator (M) and islet mRNA expression as a phenotypic outcome (E). Left diagram: The causal or methylation mediated model. Middle diagram: The reactive or methylation-consequential model (reverse causality). Right diagram: The independent model. (B) Illustration of the study approach to identify if DNA methylation of CpG sites potentially mediates the causal association between SNPs and islet mRNA expression. Left: Workflow steps. Middle: Tested relationships between G, M and E in the different steps. Right: Number of identified sites in each step. Bottom: Conditions that must be fulfilled to conclude a mathematical definition of a causal relationship between G, M and E. Significantly called as causal at 5% FDR (causal hypothesis Q<0.05).