Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts.

Pre-pregnancy obesity (ppOB) is linked to pregnancy complications and abnormal fetal growth through placental mechanisms, and long non-coding RNAs (lncRNAs) may play an epigenetic role in these processes. We investigated overall and sex-specific associations of pre-pregnancy body mass index (ppBMI), ppOB, and birthweight with placental lncRNA transcripts in two birth cohorts. Study participants were mother-child dyads recruited to the CANDLE (Memphis, TN)( = 725) and GAPPS (Seattle and Yakima, WA)( = 159) cohorts. Maternal ppBMI was assessed at enrollment using interviewer-administered questionnaires. LncRNAs (1,077 and 1,033 for CANDLE and GAPPS, respectively) were sequenced from placental samples collected at birth. Placental lncRNA was regressed on ppBMI, ppOB (ppBMI ≥30kg/m), or continuous birthweight in cohort-specific weighted linear models controlling for -specified confounders and experimental variables. Potential effect modification by infant-sex was examined in sex-stratified analyses and models including BMI-infant-sex interaction terms. No lncRNA transcripts were significantly associated with ppBMI, ppOB, or birthweight in primary models. Among male infants in CANDLE, expression of three lncRNA transcripts (, , ) was associated with ppBMI and one transcript () with birthweight. In GAPPS, ppBMI was associated with two lncRNA transcripts ( and ) among males, and birthweight was associated with 17 lncRNA transcripts (including , , and ) among females. No BMI-infant-sex interactions were observed. Though many of these potential associations are for uncharacterized transcripts, several identified lncRNAs (e.g., and ) have been linked to pathways controlling cancer or placental growth, trophoblast differentiation, and gene expression. These associations warrant validation in future studies.