Identifying fenofibrate responsive CpG sites

摘要

As part of GAW20, we analyzed the familiality and variability of methylation to identify cytosine-phosphate-guanine (CpG) sites responsive to treatment with fenofibrate. Methylation was measured at approximately 450,000 sites in pedigree members, prior to and after 3?weeks of treatment. Initially, we aimed to identify responsive sites by analyzing the pre- and posttreatment methylation changes within individuals, but these data exhibited a confounding treatment/batch effect. We applied an alternative indirect approach by searching for CpG sites whose methylation levels exhibit a genetic response to the drug. We reasoned that these sites would exhibit highly familial and variable methylation levels posttreatment, but not pretreatment. Using a 0.1% threshold, posttreatment sibling correlation (scor) and standard deviation (SD) distributions share 16 outliers, while the corresponding pretreatment distributions share none. Comparing the pre- and posttreatment CpG outliers, 36 (8%) of SD distributions, and 449/450 (nearly 100%) of scor distributions differ. Combined, these results identify methylation sites within the KIAA1804 and ANAPC2 genes. Each gene also has a highly significant methylation quantitative trait locus (meQTL) ( KIAA1804: p.