meQTL analysis

The DNA samples from the patients in this study were also genotyped using the Illumina HumanCoreExome-24-v1-0 according to the manufacturer’s protocol (Illumina). The raw genotype data were assessed using GenomeStudio, where samples <90% call rate were excluded and the data was clustered. Data were exported to PLINK v1.07 [19] where variants and individuals with <98% call rate were excluded. Each chromosome was aligned to The 1000 Genomes Project Phase 3 reference panel using shapeit.v2.r837 [20]. The imputation was performed using impute2_2.3.2. From the imputed dataset, whole chromosomal regions pertaining to the replicated CpG regions were extracted using PLINK v1.07. Using the methylation values from the epigenome-wide data and the corresponding genome-wide single nucleotide polymorphism (SNP) data, SNPs mapped to within 1 million bases around the replicated CpGs were investigated for cis-acting meQTLs using the R package, matrixEQTL [21].