Abstract
Epigenome-wide association studies (EWAS) have traditionally focused on the association test of single epigenetic markers with complex traits. However, it is possible that multiple cytosine-phosphate-guanine (CpG) sites at the same locus could jointly exert their effects on human traits. Therefore, a region-based test that combines multiple markers could be more powerful. We used 2 different region-based tests to investigate the association between changes in DNA methylation and drug response, including the median methylation level test (MMLT) and sequence kernel association test (SKAT). No genes were found to be significantly associated with the drug response (for triglycerides, the false discovery rate ranged from 0.855 to 0.999; for high-density lipoprotein cholesterol, and the false discovery rate ranged from 0.584 to 0.915). Further evidence is needed to explore potential application of gene-level methylation association analysis.
Highlights
Considerable interindividual variabilities of responses have been observed in people who take lipid-lowering drugs, underscoring the importance of genetic variants to the drug response
The objective of this study is to investigate whether region-based changes of methylation profiles are associated with lipid changes induced by fenofibrate treatment in a family-based population
The triglyceride level tended to decrease while high-density lipoprotein cholesterol (HDL-C) increased after 3 weeks of fenofibrate intervention
Summary
Considerable interindividual variabilities of responses have been observed in people who take lipid-lowering drugs, underscoring the importance of genetic variants to the drug response. Das et al performed an epigenome-wide association study (EWAS) to test the association of each individual cytosine-phosphate-guanine (CpG) site with lipid levels before and after 3 weeks of fenofibrate treatment [2]. It is interesting to explore region-based tests, which could use the information from multiple CpG sites and examine their joint effects on drug response. Such analysis can be a complement to current single-CpG association studies. The objective of this study is to investigate whether region-based changes of methylation profiles are associated with lipid changes induced by fenofibrate treatment in a family-based population
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