DNA Methylation Near DLGAP2 May Mediate the Relationship between Family History of Type 1 Diabetes and Type 1 Diabetes Risk

Figure 2

Analysis results for DLGAP2 probes with significant associations at each step (cg00565786, cg27351978). (a) Mediator model results from robust linear regression of the association between family history of T1D and methylation. (b) Outcome model interaction where the difference in methylation between T1D cases and controls differed by a family history of T1D—among those with an affected mother, cases had decreased methylation compared to controls, while the opposite relationship was seen among those with an affected father or no family history of T1D. (c) Mediation effect estimation combining the mediator and outcome model results. The significant indirect effect (PNIE) indicates that for those with an affected mother, the risk for T1D was mediated through DNA methylation at these locations. (d) Methylation associations with changes to cis-gene expression. PNIE, pure natural indirect effect; TNDE, total natural direct effect. All methylation was modeled on the M-value scale.

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