In order to test whether the 719 genome-wide significant SNPs affect methylation we performed meQTL analyses. Methylation probes targeting CpG sites within the 4.2 Mb target region (i.e. the region with genome-wide significant association signal) with 500 kb flanking regions were identified from the Infinium HumanMethylation450 BeadChip (Illumina) data available in 171 FinnTwin12 and FinnTwin16 subjects included in the NMR GWAS. Array preprocessing and normalization was performed using the Bioconductor package ‘minfi’ [46], with Stratified Quantile Normalization using the function PreprocessQuantile. Altogether 2268 methylation probes map to the 4.2 Mb target region; 844 of these were excluded as they have been reported as unreliable based on various criteria (mapping to multiple genomic locations and known repeat regions, containing SNPs, etc.) [47]. Variance in methylation levels was estimated in the remaining 1424 CpG sites; as we had a limited sample size (N = 171) and thus limited power to detect association, we restricted the meQTL analyses to 158 CpG sites with reasonable variance (interquartile range ≥0.05; S2 Fig). We constructed linear regression models of DNA methylation levels at each CpG site
