Pooling-based genetic mapping of DNA methylation

DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have attempted to understand the role of methylation by mapping genetic variants that are associated with DNA methylation, but these have been limited to microarrays that cover less than 2% of the genome. We present a novel approach in which bisulfite-treated DNA from many individuals is sequenced together in a single pool, resulting in a truly genome-wide map of DNA methylation. Pooling samples increases statistical power to detect associations, while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from the pooled DNA of 60 human cell lines.