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

摘要

Due to errors in production, Figure 2 and Figure 4 are incorrect. The correct versions are provided here. 10.1371/journal.pgen.1004735.g002 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. 10.1371/journal.pgen.1004735.g004 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).