Placental epigenetic clocks derived from crowdsourcing: Implications for the study of accelerated aging in obstetrics.

Epigenetic gestational age acceleration has been implicated in obstetric syndromes including preeclampsia, yet robust conclusions require accurate and unbiased epigenetic age models. Herein, we curated 1,842 public placental methylomes and organized a DREAM challenge to develop models of gestational age. Participants were blinded to the test data that we generated from 384 placentas encompassing normal and complicated pregnancies.

Maternal parity modifies the association of birthweight polygenic score with fetal growth.

Low birthweight is more common among children born to nulliparas (women with no prior pregnancy lasting ≥20 weeks of gestation) compared to those born to multiparas (women with one or more prior pregnancies lasting ≥20 weeks). We investigated whether parity modifies the association of maternal genetic risk score (mGRS) of maternal birthweight-reducing genetic variants with fetal size and weekly growth pace (i.e.

Association of placental weight and placental-fetal weight ratio with DNA methylation in placenta.

Aim: To investigate the association between placental methylation and placenta weight (PW) and placental-fetal weight ratio (PFR), which are markers of placental function linked to adverse pregnancy outcomes and risk for diseases in later life.

Methods: We examined the association between placental epigenome-wide methylation and PW and PFR at birth ( = 301). Further tests assessed whether methylation levels of the cytosine-guanine sites (CpGs) linked to PW and PFR are associated with placental expression of nearby genes.

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.

Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases.

Sex differences in physiological and disease traits are pervasive and begin during early development, but the genetic architecture of these differences is largely unknown. Here, we leverage the human placenta, a transient organ during pregnancy critical to fetal development, to investigate the impact of sex in the regulatory landscape of placental autosomal methylome and transcriptome, and its relevance to health and disease. We find that placental methylation and its genetic regulation are extensively impacted by fetal sex, whereas sex differences in placental gene expression and its genetic regulation are limited.

Maternal obesity and ancestry distance in influencing birth outcomes.

Background: Maternal pre-pregnancy obesity has been associated with birth outcomes, but the influence of genetic distance (GD) on this relationship is unclear. Therefore, the objective of this study was to assess the interplay of GD and maternal obesity on birthweight, placental weight, and large for gestational age (LGA).

Methods: We used data from the NICHD Fetal Growth Studies-Singletons cohort, a prospective cohort study of multi-ancestral pregnant women.

Contribution of county-level socioeconomic indicators to racial or ethnic differences in neonatal anthropometry in the USA: a prospective cohort study.

Introduction: Racial and ethnic differences in fetal growth and birth size in the USA have not been adequately explained by individual-level socioeconomic status (SES) factors. We explored whether differences may be partially explained by county-level indicators of SES.

Methods: We linked participant zip codes from the National Institute of Child Health and Human Development Fetal Growth Studies (2009-2013; n=1614) to county-level US census data to calculate a neighbourhood deprivation index, education isolation index and two indices of segregation: racial isolation and evenness.

Longitudinal maternal glycemia during pregnancy and placental epigenetic age acceleration.

Background: Dysregulation of maternal glucose homeostasis has been related to an increased risk of morbidity and mortality in mothers and fetuses, yet the mechanism remains unclear. This study investigated the association between maternal glycemic levels and placental epigenetic age acceleration (PAA) in a multiethnic cohort.

Methods: In a sample of 301 pregnant women (102 Hispanic, 77 White, 72 Black, and 50 Asian/Pacific Islander), the association of glycemic markers cumulative exposure with PAA was tested using linear regression adjusting for fetal sex, maternal age, educational status, and health insurance status.

Multi-omics approaches for understanding gene-environment interactions in noncommunicable diseases: techniques, translation, and equity issues.

Non-communicable diseases (NCDs) such as cardiovascular diseases, chronic respiratory diseases, cancers, diabetes, and mental health disorders pose a significant global health challenge, accounting for the majority of fatalities and disability-adjusted life years worldwide. These diseases arise from the complex interactions between genetic, behavioral, and environmental factors, necessitating a thorough understanding of these dynamics to identify effective diagnostic strategies and interventions. Although recent advances in multi-omics technologies have greatly enhanced our ability to explore these interactions, several challenges remain.

Maternal Glycemic Status and Longitudinal Fetal Body Composition and Organ Volumes Based on Three-Dimensional Ultrasonography.

Objective: Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth as measured by two-dimensional ultrasonography. Whether fetal three-dimensional (3D) soft tissue and organ volumes provide additional insight into fetal overgrowth is unknown.

Research Design And Methods: We prospectively evaluated longitudinal 3D fetal body composition and organ volumes in a diverse U.

Genetic distance and ancestry proportion modify the association between maternal genetic risk score of type 2 diabetes and fetal growth.

Background: Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry is not yet fully understood. We aimed to investigate the influence of genetic distance (GD) and genetic ancestry proportion (GAP) on the association of maternal genetic risk score of T2D (GRS) with fetal weight and birthweight.

Methods: Multi-ancestral pregnant women (n = 1,837) from the NICHD Fetal Growth Studies - Singletons cohort were included in the current analyses.

Placental accelerated aging in antenatal depression.

Background: Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores.

Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores.

Plasma Amino Acids in Early Pregnancy and Midpregnancy and Their Interplay With Phospholipid Fatty Acids in Association With the Risk of Gestational Diabetes Mellitus: Results From a Longitudinal Prospective Cohort.

Objective: We prospectively evaluated plasma amino acids (AAs) in early pregnancy and midpregnancy and their interplay with phospholipid fatty acids (FAs) in association with gestational diabetes mellitus (GDM) risk.

Research Design And Methods: From a longitudinal pregnancy cohort of 2,802 individuals, concentrations of 24 plasma AAs at 10-14 and 15-26 gestational weeks (GW) were assessed among 107 GDM case subjects and 214 non-GDM control subjects. We estimated adjusted odds ratios (OR) and 95% CI for the associations of plasma AAs and the joint associations of plasma AAs and phospholipid FAs with GDM risk, adjusting for risk factors including age, prepregnancy BMI, and family history of diabetes.

Prenatal social support in low-risk pregnancy shapes placental epigenome.

Background: Poor social support during pregnancy has been linked to inflammation and adverse pregnancy and childhood health outcomes. Placental epigenetic alterations may underlie these links but are still unknown in humans.

Methods: In a cohort of low-risk pregnant women (n = 301) from diverse ethnic backgrounds, social support was measured using the ENRICHD Social Support Inventory (ESSI) during the first trimester.

Genomic study of maternal lipid traits in early pregnancy concurs with four known adult lipid loci.

Background: Blood lipids during pregnancy are associated with cardiovascular diseases and adverse pregnancy outcomes. Genome-wide association studies (GWAS) in predominantly male European ancestry populations have identified genetic loci associated with blood lipid levels. However, the genetic architecture of blood lipids in pregnant women remains poorly understood.

Familial aggregation of stillbirth: A pedigree analysis of a matched case-control study.

Objective: To determine whether stillbirth aggregates in families and quantify its familial risk using extended pedigrees.

Design: State-wide matched case-control study.

Setting: Utah, United States.

The association between first-trimester omega-3 fatty acid supplementation and fetal growth trajectories.

Background: Prenatal omega-3 fatty acid supplementation, particularly docosahexaenoic acid and eicosapentaenoic acid, has been associated with greater birthweight in clinical trials; however, its effect on fetal growth throughout gestation is unknown.

Objective: This study aimed to examine the association between first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation and growth trajectories of estimated fetal weight and specific fetal biometrics measured longitudinally from the second trimester of pregnancy to delivery.

Study Design: In a multisite, prospective cohort of racially diverse, low-risk pregnant women, we used secondary data analysis to examine fetal growth trajectories in relation to self-reported (yes or no) first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation.

Including diverse and admixed populations in genetic epidemiology research.

The inclusion of ancestrally diverse participants in genetic studies can lead to new discoveries and is important to ensure equitable health care benefit from research advances. Here, members of the Ethical, Legal, Social, Implications (ELSI) committee of the International Genetic Epidemiology Society (IGES) offer perspectives on methods and analysis tools for the conduct of inclusive genetic epidemiology research, with a focus on admixed and ancestrally diverse populations in support of reproducible research practices. We emphasize the importance of distinguishing socially defined population categorizations from genetic ancestry in the design, analysis, reporting, and interpretation of genetic epidemiology research findings.