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Context Clarification of the association among phenotypes, genetic, and environmental factors with clinical laboratory traits can reveal the cause of diseases and assist in developing methods for the prediction and prevention of diseases. It is difficult to investigate the environmental effect on phenotypes using individual samples because their genetic and environmental factors differ, but we can easily investigate the influence of environmental factors using monozygotic (MZ) twins because they have the same genetic factors. Objective We aimed to examine the methylation level of CpG sites as an environmental factor affecting adiponectin levels on the basis of the same genetic background using MZ twins and to identify the epigenetic factors related to adiponectin levels and the genetic factors associated with sensitivity to acquired changes in adiponectin. Methods Using 2 groups built from each twin of 232 MZ twin pairs, we performed a replicated epigenome-wide association study to clarify the epigenetic factors affecting adiponectin levels adjusted by genetic risk score. Moreover, we divided twin pairs into concordant and discordant for adiponectin levels. We conducted a genome-wide association study to identify a genetic background specific for discordance. Results Methylation levels at 38 CpG sites were reproducibly associated with adjusted adiponectin levels, and some of these CpG sites were in genes related to adiponectin, including CDH13. Some genes related to adiponectin or insulin resistance were found to be genetic factors specific for discordance. Conclusion We clarified specific epigenetic factors affecting adiponectin levels and genetic factors associated with sensitivity to acquired changes in adiponectin. |
