Fig. 2: Methylome-wide association studies (MWAS) of 4058 plasma proteins.

a Summary of MWAS results for 4058 protein levels in Generation Scotland (N = 774). The number of protein quantitative trait methylation loci (pQTMs) that had P < 4.5 × 10⁻¹⁰ (Bonferroni threshold for multiple testing adjustment) in the basic, white blood cell proportion (WBC)-adjusted and fully-adjusted models. Cis associations (purple) and trans associations (green) are summarised for each model. Covariates used to adjust DNAm are described for each model. Normalised protein levels were adjusted for age, sex, 20 genetic principal components (PCs), protein quantitative trait loci (pQTLs) and technical variables and scaled to have a mean of 0 and standard deviation of 1. Results were generated through linear regression models. Full summary statistics with full P values can be accessed in Supplementary Data 6. Created with BioRender.com. b Flow diagram showing the distinction between the highly pleiotropic PAPPA and PRG3 protein pQTMs and the 825 pQTMs that involved the levels of a further 189 proteins. TSS: transcriptional start site of the protein gene. The 434 cis pQTMs (purple) lay on the same chromosome and ≤ 10 Mb from the transcriptional start site (TSS) of the protein gene, whereas the 391 trans pQTMs (green) lay >10 Mb from the TSS of the protein gene or on a different chromosome. Created with BioRender.com. c Genomic locations for 825 of the 2928 fully-adjusted pQTMs, excluding highly pleotropic associations for PAPPA and PRG3 protein levels, with cis pQTMs in purple and trans pQTMs in green. Chromosomal location of CpG sites (x-axis) and protein genes (y-axis) are presented. A list of the full association counts for each protein and CpG site can be found in Supplementary Data 8, 9.