Biology subjects

Hoyo, C.

Publications and source records attributed to Hoyo, C..

6 recordsLinked to original sources

bioRxiv2025

Effects of Ambient Temperature During Pregnancy on Newborn Birthweight

This study evaluates the association between ambient temperature exposure during pregnancy and newborn birthweight, using a penalized generalized additive model (GAM) framework with distributed lag non-linear models (DLNM) to identify sensitive windows of exposure. The analysis includes 238 participants from the SHIP study with complete temperature exposure and birthweight data. Weekly maximum temperatures during pregnancy were estimated using Daymet data, and the impact of temperature on birthweight was assessed, adjusting for maternal age, pre-pregnancy BMI, gestational age, race, smoking, diabetes status, and infant biological sex. The model incorporated a crossbasis function for temperature exposure across 42 gestational weeks and allowed penalization for smoother, data-driven lag estimation. Results from the combined-sex model indicated that higher ambient temperatures during the third trimester, particularly in the final weeks of pregnancy, were associated with increased birthweight. Stratified analyses suggested that this association was more pronounced in male infants. These findings highlight the importance of considering prenatal temperature exposures and timing when evaluating determinants of newborn health.

developmental biology↗

bioRxiv2024

Creation and Validation of the First Infinium DNA Methylation Array for the Human Imprintome

BackgroundDifferentially methylated imprint control regions (ICRs) regulate the monoallelic expression of imprinted genes. Their epigenetic dysregulation by environmental exposures throughout life results in the formation of common chronic diseases. Unfortunately, existing Infinium methylation arrays lack the ability to profile these regions adequately. Whole genome bisulfite sequencing (WGBS) is the unique method able to profile these regions, but it is very expensive and it requires not only a high coverage but it is also computationally intensive to assess those regions. FindingsTo address this deficiency, we developed a custom methylation array containing 22,819 probes. Among them, 9,757 probes map to 1,088 out of the 1,488 candidate ICRs recently described. To assess the performance of the array, we created matched samples processed with the Human Imprintome array and WGBS, which is the current standard method for assessing the methylation of the Human Imprintome. We compared the methylation levels from the shared CpG sites and obtained a mean R2 = 0.569. We also created matched samples processed with the Human Imprintome array and the Infinium Methylation EPIC v2 array and obtained a mean R2 = 0.796. Furthermore, replication experiments demonstrated high reliability (ICC: 0.799-0.945). ConclusionsOur custom array will be useful for replicable and accurate assessment, mechanistic insight, and targeted investigation of ICRs. This tool should accelerate the discovery of ICRs associated with a wide range of diseases and exposures, and advance our understanding of genomic imprinting and its relevance in development and disease formation throughout the life course.

genetics↗

bioRxiv2023

An epigenome-wide association study of child appetitive traits and DNA methylation

Childhood appetitive traits are consistently associated with obesity risk, and yet their etiology is poorly understood. Appetitive traits are complex phenotypes which are hypothesized to be influenced by both genetic and environmental factors, as well as their interactions. Early-life epigenetic processes, such as DNA methylation (DNAm), may be involved in the developmental programming of appetite regulation in childhood. In the current study, we meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n=1,086, Rotterdam, the Netherlands) and the Healthy Start study (n=236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their childs food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Childrens Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait at the individual site-level. However, at the regional level, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.

genetics↗

bioRxiv2019

Association between DNA methylation and ADHD symptoms from birth to school age: A prospective meta-analysis

Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is not known. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school-age. We examined associations of DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age range 4-15 years) in 2477 children from five cohorts and DNA methylation at school-age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from ten cohorts. CpGs identified with nominal significance (p<0.05) in either of the EWAS were correlated between timepoints ({rho}=0.30), suggesting overlap in associations, however, top signals were very different. At birth, we identified nine CpGs that were associated with later ADHD symptoms (P<1*10-7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 located in the promotor region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which was associated with neurite outgrowth and an ADHD diagnosis in previous studies. In contrast, at school-age, no CpGs were associated with ADHD with P<1*10-7. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.

genetics↗

bioRxiv2019

Replicated Umbilical Cord Blood DNA Methylation Loci Associated with Gestational Age at Birth

BackgroundDNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The fetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behavior of individual genes.\n\nObjectivesThe aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in matched specimens.\n\nResultsGenome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450K BeadChip, was associated with GA for 2,372 CpG probes (5% false discovery rate) in both the Pregnancy, Race, Environment, Genes (PREG - Virginia Commonwealth University) and Newborn Epigenetic Study (NEST - Duke University) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. This assessment provides a strong evidence to support the importance of DNAm change throughout the gestational time period.\n\nConclusionsThese results converge on support for the role of variation in DNAm measures as an important genetic regulatory mechanism contributing to inter-individual differences in gestational age at birth. In particular, the pathways described are consistent with the well-known hypothesis of pathogen detection and response by the immune system to elicit premature labor as a consequence of unscheduled inflammation.

genomics↗

bioRxiv2017

Cadmium Exposure Increases The Risk Of Juvenile Obesity: A Human And Zebrafish Comparative Study

OBJECTIVEHuman obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and a zebrafish model of adipogenesis.\n\nDESIGNAn extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) were analyzed for the presence Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age five years. Next, the role of Cd as a potential obesogen was analyzed in an in vivo zebrafish model.\n\nRESULTSOur analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.\n\nCONCLUSIONOur findings identify Cd as potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations.

epidemiology↗