Mediating effects of DNA methylation on the association of sleep quality with infertility among women of childbearing age

Abstract

Background To investigate the association between sleep quality and infertility in Chinese females and to explore the mediating effects of DNA methylation. Methods This study was based on the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC) study in China. We used the Illumina Infinium Human Methylation 850k BeadChip to detect changes in DNA methylation in peripheral blood samples. Here, we compared the relationship between female sleep characteristics and infertility in females with anovulatory infertility (n = 43) and healthy female controls (n = 43). A total of 753 354 CpG sites were included in the final analysis. We identified differentially methylated sites between cases and controls using the R package ChAMP. The R package “mediation” Bayesian estimation method was used to investigate the mediation effect between sleep quality and infertility among women. Results Of the 753 354 probes on the EPIC Beadchips analyzed, a total of 763 differentially methylated CpG sites corresponding to 476 genes were identified, including 540 hypermethylated sites and 223 hypomethylated sites. Difficulty falling asleep was a risk factor for infertility in females, and a causal mediation effect of DNA methylation sites was found (cg07675898, cg08298632 and cg15500907). Conclusions These results suggest that DNA methylation sites play a significant role between difficulty falling asleep and infertility in women, and a total of three methylation sites (cg07675898, cg08298632 and cg15500907) were found to be mediating variables. With the help of causal mediation analysis, the mediation effect of DNA methylation between difficulty falling asleep and female infertility provided new clues for the prevention and treatment of female infertility.