Whole-Genome Sequencing
We performed whole-genome sequencing in order to identify any potential unique variants present in individuals with promoter methylation and not in unaffected individuals. PCR-free paired-end whole-genome sequencing (TruSeq DNA PCR-Free, Illumina) was undertaken on a HiSeqX platform. Reads were aligned against the human assembly GRCh38 (UCSC Genome Browser) via the Burrows-Wheeler Aligner (v.0.6.2), and variants were called with the Genome Analysis Toolkit (3.4-0-g7e26428). Annotation was performed with Ensembl v.89 and compared with variation identified in the Genome Aggregation Database (gnomAD)21 (Supplemental Material and Methods).