| 1. |
- Schlosser, P, et al.
(author)
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Meta-analyses identify DNA methylation associated with kidney function and damage
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
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Journal article (peer-reviewed)abstract
- Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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| 2. |
- Liu, C, et al.
(author)
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A DNA methylation biomarker of alcohol consumption.
- 2018
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
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Journal article (peer-reviewed)abstract
- The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
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| 3. |
- Pearce, Neil E, et al.
(author)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 4. |
- Tin, A, et al.
(author)
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
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Journal article (peer-reviewed)abstract
- Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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| 5. |
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| 6. |
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| 7. |
- Jhun, Mina-A, et al.
(author)
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
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| 8. |
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| 9. |
- Merid, Simon Kebede, et al.
(author)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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In: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Journal article (peer-reviewed)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 10. |
- Rosa, M. J., et al.
(author)
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Identifying critical windows of prenatal particulate matter (PM2.5) exposure and early childhood blood pressure
- 2020
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In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 182
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Journal article (peer-reviewed)abstract
- Background: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Some evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 μm in diameter (PM2.5) exposure and children's BP at ages 4–6 years. Methods: Participants included 537 mother-child dyads enrolled in the Programming Research in Obesity, GRowth Environment, and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used distributed lag models (DLMs) to examine associations between daily PM2.5 exposure and systolic and diastolic BP (SBP and DBP), adjusting for child's age, sex and BMI, as well as maternal education, preeclampsia and indoor smoking report during the second and third trimester, seasonality and average postnatal year 1 PM2.5 exposure. Results: We found that PM2.5 exposure between weeks 11–32 of gestation (days 80–226) was significantly associated with children's increased SBP. Similarly, PM2.5 exposure between weeks 9–25 of gestation (days 63–176) was significantly associated with increased DBP. To place this into context, a constant 10 μg/m3 increase in PM2.5 sustained throughout this critical window would predict a cumulative increase of 2.6 mmHg (CI: 0.5, 4.6) in SBP and 0.88 mmHg (CI: 0.1, 1.6) in DBP at ages 4–6 years. In a stratified analysis by sex, this association persisted in boys but not in girls. Conclusions: Second and third trimester PM2.5 exposure may increase children's BP in early life. Further work investigating PM2.5 exposure with BP trajectories later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations, including pregnant women.
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| 11. |
- Kupers, LK, et al.
(author)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Journal article (peer-reviewed)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 12. |
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| 13. |
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| 14. |
- Holliday, Katelyn M., et al.
(author)
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Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of US adults
- 2022
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In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 212
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Journal article (peer-reviewed)abstract
- Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO2; NOx), ozone (O-3), and sulfur dioxide (SO2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation-and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (P-Cochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression.
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| 15. |
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| 16. |
- Sikdar, S, et al.
(author)
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Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking
- 2019
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In: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 11:13, s. 1487-1500
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Journal article (peer-reviewed)abstract
- Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.
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| 17. |
- Volski, V., et al.
(author)
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Overview of the software integration activities within ACE
- 2006
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In: First European Conference on Antennas and Propagation (EuCAP), 2006, Nice, France, 6 - 10 November 2006. - : IEEE. - 0379-6566. - 9789290929376 ; 626 SP
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Conference paper (peer-reviewed)abstract
- The ACE project initiated the start of several integration activities between European institutions involved in electromagnetic modeling of antennas with planar or conformal topologies. The goal of the integration activities was / is not to create a global software package that integrates the software of all partners, but to initiate a long term process for antenna software integration activities within the European antenna community. During the first two years of ACE the integration activities were performed in several groups with a rather small number of partners in each group. The groups were formed by partners who wanted to integrate a specific approach developed by one partner into the software code of another partner. This allows increasing the capability and efficiency of a software code. In this paper a short overview of all integration activities is given.
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| 18. |
- Zhong, Jia, et al.
(author)
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B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:13, s. 3503-3508
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Journal article (peer-reviewed)abstract
- Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4(+) T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (Pinteraction = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM2.5 effects, with possible significant public health benefit in areas with frequent PM2.5 peaks.
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| 19. |
- Jauregui, Alejandra, et al.
(author)
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Physical activity, sedentary time and cardiometabolic health indicators among Mexican children
- 2020
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In: Clinical Obesity. - : Wiley-Blackwell. - 1758-8103 .- 1758-8111. ; 10:1
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Journal article (peer-reviewed)abstract
- We examined the independent associations of moderate to vigorous physical activity (MVPA) and sedentary time (ST) with cardiometabolic indicators in Mexican children (4-6 years of age). We conducted a cross-sectional study (n = 400) using the measures of MVPA and ST (7-day accelerometry) and the following indicators: % body fat, waist circumference, body mass index (BMI) z-score, glycated haemoglobin, blood glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, leptin, adiponectin and resting blood pressure. We examined the independent associations of MVPA and ST with cardiometabolic indicators through confounder-adjusted and mutually adjusted (including both MVPA and ST) linear regression models. Confounder-adjusted models showed that MVPA was associated with higher BMI z-scores and lower adiponectin levels in girls and lower body fat among boys. ST was associated with higher body fat, in the full sample, and lower LDL cholesterol among boys. After mutually adjusting for MVPA and ST, MVPA (10-minute increase) remained significantly associated with BMI z-score in girls (beta = 0.187, 95% CI: 0.019, 0.356) and ST (60-minute increase) remained significantly associated with higher body fat (beta = 1.11%, 95% CI: 0.019, 2.203) among boys and higher glycated haemoglobin (beta = 0.047% points, 95% CI: 0.000, 0.094) in the full sample. In preschool-aged children, the objective measures of ST and MVPA were associated with small differences in cardiometabolic health indicators. ST was unfavourably associated with some cardiometabolic indicators even after adjusting for MVPA, and thus appeared to have a more significant role than MVPA, especially in boys. Future longitudinal studies should confirm these results.
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| 20. |
- Karlsson, Oskar, et al.
(author)
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Detection of long non-coding RNAs in human breastmilk extracellular vesicles : Implications for early child development.
- 2016
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In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 11:10, s. 721-729
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Journal article (peer-reviewed)abstract
- Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho>0.9; P<0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.
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| 21. |
- Karlsson, Oskar, et al.
(author)
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Environmental Health and Long Non-coding RNAs.
- 2016
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In: Current environmental health reports. - : Springer Science and Business Media LLC. - 2196-5412. ; 3:3, s. 178-87
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Journal article (peer-reviewed)abstract
- An individual's risk of developing a common disease typically depends on an interaction of genetic and environmental factors. Epigenetic research is uncovering novel ways through which environmental factors such as diet, air pollution, and chemical exposure can affect our genes. DNA methylation and histone modifications are the most commonly studied epigenetic mechanisms. The role of long non-coding RNAs (lncRNAs) in epigenetic processes has been more recently highlighted. LncRNAs are defined as transcribed RNA molecules greater than 200 nucleotides in length with little or no protein-coding capability. While few functional lncRNAs have been well characterized to date, they have been demonstrated to control gene regulation at every level, including transcriptional gene silencing via regulation of the chromatin structure and DNA methylation. This review aims to provide a general overview of lncRNA function with a focus on their role as key regulators of health and disease and as biomarkers of environmental exposure.
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| 22. |
- Levin-Schwartz, Yuri, et al.
(author)
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Exosomal miRNAs in urine associated with children's cardiorenal parameters : A cross-sectional study
- 2021
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In: Epigenetics. - : Future Medicine Ltd. - 1559-2294 .- 1559-2308. ; 13:7, s. 499-512
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Journal article (peer-reviewed)abstract
- Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & Methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.
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| 23. |
- Machtinger, Ronit, et al.
(author)
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Placental lncRNA Expression Is Associated With Prenatal Phthalate Exposure
- 2018
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In: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 163:1, s. 116-122
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Journal article (peer-reviewed)abstract
- Phthalates are endocrine-disrupting chemicals that can cross the placenta and affect the fetal epigenome. Among various epigenetic regulators of gene expression, long noncoding RNAs (lncRNAs) are important players that may also be involved in the manifestation of endocrine-disrupting chemical toxicity. We sought to explore the association between maternal urinary phthalate metabolite concentrations and lncRNA expression in human placenta to better understand potential mechanisms through which lncRNAs participate in mediating phthalate toxicity. Ten patients with uncomplicated dichorionic diamniotic twin pregnancies at term were included in this study. Urinary (n = 10) and placenta samples (n = 20) were collected for all participants. Urinary samples were analyzed for 15 phthalate metabolites and 2 phthalate alternative metabolites. Real-time PCR arrays were used to identify and quantify 87 lncRNAs from the placental samples. We tested the Spearman correlation matrix to compare prenatal phthalate measures against placental lncRNA levels. lncRNA levels showed large variations across samples, with no significant differences in lncRNA expression within twin pairs. Mono-(carboxynonyl) phthalate demonstrated consistently strong correlations with most lncRNAs. The strongest correlation was observed between mono-hydroxyisobutyl phthalate and LOC91450 (Rspearman = 0.88, p < .001). This correlation remained significant after Bonferroni adjustment. Other strong correlations were observed between mono-isobutyl phthalate, DPP10 and HOTTIP (Rspearman = −0.91, p < .001). AIRN, DACT3.AS1, DLX6, DPP10, HOTTIP, LOC143666, and LOC91450 were strongly correlated with the greatest number of phthalate metabolites. Further studies are needed to validate these results and understand if the altered expression of lncRNAs in human placenta has clinical significance.
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| 24. |
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| 25. |
- Wong, Sandy, et al.
(author)
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Associations between daily ambient temperature and sedentary time among children 4-6 years old in Mexico City
- 2020
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:10
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Journal article (peer-reviewed)abstract
- Background Sedentary behavior is a worldwide public health concern. There is consistent and growing evidence linking sedentary behavior to mortality and morbidity. Early monitoring and assessment of environmental factors associated with sedentary behaviors at a young age are important initial steps for understanding children's sedentary time and identifying pertinent interventions. Objective This study examines the association between daily temperature (maximum, mean, minimum, and diurnal variation) and all-day sedentary time among 4-6 year old children in Mexico City (n = 559) from the year 2013 to 2015. Methods We developed a spatiotemporally resolved hybrid satellite-based land use regression temperature model and calculated percent daily sedentary time from aggregating 10-second epoch vertical counts captured by accelerometers that participants wore for one week. We modeled generalized additive models (GAMs), one for each temperature type as a covariate (maximum, mean, minimum, and diurnal variation). All GAMs included percent all-day sedentary time as the outcome and participant-level random intercepts to account for repeated measures of sedentary time. Our models were adjusted for demographic factors and environmental exposures. Results Daily maximum temperature, mean temperature, and diurnal variation have significant negative linear relationships with all-day sedentary time (p<0.01). There is no significant association between daily minimum temperature and all-day sedentary time. Children have on average 0.26% less daily sedentary time (approximately 2.2 minutes) for each 1 degrees C increase in ambient maximum temperature (range 7.1-30.2 degrees C), 0.27% less daily sedentary time (approximately 2.3 minutes) for each 1 degrees C increase in ambient mean temperature (range 4.3-22.2 degrees C), and 0.23% less daily sedentary time (approximately 2.0 minutes) for each 1 degrees C increase in diurnal variation (range 3.0-21.6 degrees C). Conclusions These results are contrary to our hypothesis in which we expected a curvilinear relationship between temperature (maximum, mean, minimum, and diurnal variation) and sedentary time. Our findings suggest that temperature is an important environmental factor that influences children's sedentary behavior.
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