Fig. 7: IVW MR forest plots with CH traits as exposures.

Forest plots with OR markers (for cancers and cardiovascular/metabolic traits) or exponentiated beta coefficient (exp(beta)) markers (for blood cell traits, lipids, adiposity measures and epigenetic aging indices). ORs/exp(betas) are represented as per log-odds unit increase in genetic liability to overall CH (a) or DNMT3A-CH (b). OR/exp(beta) markers with corresponding P < 0.05 are represented by filled circles. IVW regression was used for all MR analyses, and results were not adjusted for multiple comparisons. Symbols represent OR markers and error bars represent 95% CIs. Red symbols and error bars represent results using genetic instruments comprised exclusively of genome-wide significant (P < 5 × 10−8) variants. Black symbols and error bars represent results when using genome-wide significant and sub-GWS (P < 10−5) variants in the genetic instrument. Large effect size estimates (ORs/exp(betas)) are shown in the lower panels. Sample sizes for all genome-wide association datasets used are provided in Supplementary Table 35. Full results, including from sensitivity analyses, are presented in Supplementary Tables 39 and 40. IS, ischemic stroke.