Associations between antenatal maternal asthma status and placental DNA methylation

Introduction: Maternal asthma in pregnancy is associated with adverse perinatal and child health outcomes; however, mechanisms are poorly understood. Methods: The PRogramming of Intergenerational Stress Mechanisms (PRISM) prospective pregnancy cohort characterized asthma history during pregnancy via questionnaires and quantified placental DNAm using the Illumina Infinium HumanMethylation450 BeadChip. We performed epigenome-wide association analyses (n = 223) to estimate associations between maternal active or inactive asthma, as compared to never asthma, and placental differentially methylated positions (DMPs) and differentially variable positions (DVPs). Models adjusted for maternal pre-pregnancy body mass index, smoking status, parity, age and education level and child sex. P-values were FDR-adjusted. Results: One hundred and fifty-nine (71.3%) pregnant women reported no history of asthma (never asthma), 15 (6.7%) reported inactive, and 49 (22%) reported active antenatal asthma. Women predominantly self-identified as Black/Hispanic Black [88 (39.5%)] and Hispanic/non-Black [42 (18.8%)]. We identified 10 probes at FDR<0.05 and 4 probes at FDR<0.10 characterized by higher variability in maternal active asthma compared to never asthma mapping to GPX3, LHPP, PECAM1, ATAD3C, and ARHGEF4 and 2 probes characterized by lower variation mapping to CHMP4A and C5orf24. Amongst women with inactive asthma, we identified 52 probes, 41 at FDR<0.05 and an additional 11 at FDR <0.10, with higher variability compared to never asthma; BMP4, LHPP, PHYHIPL, and ZSCAN23 were associated with multiple DVPs. No associations were observed with DMPs. Discussion: We observed alterations in placental DNAm in women with antenatal asthma, as compared to women without a history of asthma. Further research is needed to understand the impact on fetal development.