Fig. 4.

CoRSIVs show influence of periconceptional environment, correlate with gene expression, and are associated with human disease. a Seasonal variation of blood methylation at CoRSIVs, controls, and tDMRs in 233 Gambian 2-year olds [13]. Data represent CpGs showing significant seasonal variation (FDR < 20%, see “Methods”). Predicted methylation maxima for CpGs within CoRSIVs occur in conceptions at the peak of the Gambian rainy season (July–September); minima fall within the Gambian dry season (Jan–April). Seasonal patterns at control regions and tDMRs are less pronounced (Fisher’s exact test P > 0.8). b Results of analysis linking gene expression in adipose tissue, skin, and lymphoblastoid cell lines (LCL) vs. methylation in adipose tissue [26] for 645 gene-associated CoRSIVs that are informative on the HM450 array. Venn diagrams show that for most genes that show a significant association (Spearman P < 0.05) between methylation and expression in adipose tissue, methylation in adipose tissue is also associated with expression in skin or LCL. c Examples of expression vs. CoRSIV methylation data in all three tissues at the MRI1 promoter (left), the CNDP2 gene body (middle), and the 3′ end of SSNA1 (right). d Summary of an automated PubMed literature-search using PubTator. Shown are MESH code labels corresponding to the top 100 human diseases linked to CoRSIV-associated genes