Figures
Due to errors in production, Figure 2 and Figure 4 are incorrect. The correct versions are provided here.
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.
(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).
Reference
Citation: The PLOS Genetics Staff (2014) Correction: Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets. PLoS Genet 10(12): e1004886. https://doi.org/10.1371/journal.pgen.1004886
Published: December 12, 2014
Copyright: © 2014 The PLOS Genetics Staff. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.