Examination of newborn DNA methylation among women with polycystic ovary syndrome/hirsutism
Kristen J. Polinski,
Sonia L. Robinson,
Diane L. Putnick,
Rajeshwari Sundaram,
Erin Bell,
Paule V. Joseph,
James Segars,
Weihua Guan,
Robert M. Silver,
Enrique F. Schisterman,
Sunni L. Mumford,
Edwina H. Yeung
Affiliations
Kristen J. Polinski
Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Sonia L. Robinson
Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Diane L. Putnick
Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Rajeshwari Sundaram
Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Erin Bell
Department of Environmental Health Sciences, Epidemiology and Biostatistics, University at Albany School of Public Health, Albany, NY, United States
Paule V. Joseph
Section of Sensory Science and Metabolism, Division of Intramural Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, United States
James Segars
Division of Reproductive Science and Women’s Health Research, Johns Hopkins Department of Gynecology & Obstetrics, Baltimore, MD, United States
Weihua Guan
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States
Robert M. Silver
Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, United States
Enrique F. Schisterman
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Sunni L. Mumford
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Edwina H. Yeung
Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
ABSTRACTResearch suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation β-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [β(SE): −0.080 (0.010); FDR p = 0.009], cg08471713 [β(SE):0.077 (0.014); FDR p = 0.016] and cg17897916 [β(SE):0.050 (0.009); FDR p = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR p = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.
