Biomedical subjects

Martine Vrijheid

Publications and source records attributed to Martine Vrijheid.

8 recordsLinked to original sources

PubMed2026

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

Humans↗

PubMed2026

Maternal Chrono-Nutrition and Placental DNA Methylation: The BiSC Study.

The impact of diet during pregnancy on birth outcomes and child health is well established, and epigenetic changes may be one mechanism underlying such associations, but the role of meal timing (chrono-nutrition) is unclear. We conducted an epigenome-wide association study (EWAS) of maternal meal timing and placental DNAm (plaDNAm). Data came from 389 pregnant women in the Barcelona Life Study Cohort (BiSC). Chrono-nutrition and dietary data were collected at 20 weeks of pregnancy, and plaDNAm at delivery was characterized using the Illumina EPIC array. Linear robust regression models tested associations between five chrono-nutritional behaviors (time of first and last meal, nighttime fasting duration, number of eating occasions, and eating jetlag) and plaDNAm. We identified 7 CpGs significantly associated with time of last meal (Bonferroni p < 1E-08) and 63 suggestive CpGs (p < 1E-05). Hits included cg13147785 (E2F8), linked to placental cell cycle regulation, cg17665505 (DAP) and cg18303215 (ABCG5), associated with smoking and lung diseases in adults. To conclude, maternal chrono-nutrition was associated with some CpGs in the placenta, particularly time of last meal. Further studies are needed to clarify how meal timing may influence fetal development and long-term health through epigenetic mechanisms.

Humans↗

PubMed2024

Common genetic variants associated with urinary phthalate levels in children: A genome-wide study.

INTRODUCTION: Phthalates, or dieters of phthalic acid, are a ubiquitous type of plasticizer used in a variety of common consumer and industrial products. They act as endocrine disruptors and are associated with increased risk for several diseases. Once in the body, phthalates are metabolized through partially known mechanisms, involving phase I and phase II enzymes. OBJECTIVE: In this study we aimed to identify common single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) associated with the metabolism of phthalate compounds in children through genome-wide association studies (GWAS). METHODS: The study used data from 1,044 children with European ancestry from the Human Early Life Exposome (HELIX) cohort. Ten phthalate metabolites were assessed in a two-void pooled urine collected at the mean age of 8 years. Six ratios between secondary and primary phthalate metabolites were calculated. Genome-wide genotyping was done with the Infinium Global Screening Array (GSA) and imputation with the Haplotype Reference Consortium (HRC) panel. PennCNV was used to estimate copy number variants (CNVs) and CNVRanger to identify consensus regions. GWAS of SNPs and CNVs were conducted using PLINK and SNPassoc, respectively. Subsequently, functional annotation of suggestive SNPs (p-value < 1E-05) was done with the FUMA web-tool. RESULTS: We identified four genome-wide significant (p-value < 5E-08) loci at chromosome (chr) 3 (FECHP1 for oxo-MiNP_oh-MiNP ratio), chr6 (SLC17A1 for MECPP_MEHHP ratio), chr9 (RAPGEF1 for MBzP), and chr10 (CYP2C9 for MECPP_MEHHP ratio). Moreover, 115 additional loci were found at suggestive significance (p-value < 1E-05). Two CNVs located at chr11 (MRGPRX1 for oh-MiNP and SLC35F2 for MEP) were also identified. Functional annotation pointed to genes involved in phase I and phase II detoxification, molecular transfer across membranes, and renal excretion. CONCLUSION: Through genome-wide screenings we identified known and novel loci implicated in phthalate metabolism in children. Genes annotated to these loci participate in detoxification, transmembrane transfer, and renal excretion.

Humans↗

PubMed2006

The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk.

This paper examines the effects of systematic and random errors in recall and of selection bias in case-control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte-Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case-control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non-differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non-users. Where possible these selection probabilities were based on existing information from non-respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J-shaped exposure-response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case-control studies of mobile phone use and cancer risk, including the INTERPHONE study.

Case-Control Studies↗

PubMed2004

Toward the effective surveillance of hypospadias.

Concern about apparent increases in the prevalence of hypospadias--a congenital male reproductive-tract abnormality--in the 1960s to 1980s and the possible connection to increasing exposures to endocrine-disrupting chemicals have underlined the importance of effective surveillance of hypospadias prevalence in the population. We report here the prevalence of hypospadias from 1980 to 1999 in 20 regions of Europe with EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers, 14 of which implemented a guideline to exclude glanular hypospadias. We also report data from the England and Wales National Congenital Anomaly System (NCAS). Our results do not suggest a continuation of rising trends of hypospadias prevalence in Europe. However, a survey of the registers and a special validation study conducted for the years 1994-1996 in nine EUROCAT registers as well as NCAS identified a clear need for a change in the guidelines for registration of hypospadias. We recommend that all hypospadias be included in surveillance, but that information from surgeons be obtained to verify location of the meatus, and whether surgery was performed, in order to interpret trends. Investing resources in repeated special surveys may be more cost-effective than continuous population surveillance. We conclude that it is doubtful whether we have had the systems in place worldwide for the effective surveillance of hypospadias in relation to exposure to potential endocrine-disrupting chemicals.

Confounding Factors, Epidemiologic↗

PubMed2004

Risk of low birth weight near EUROHAZCON hazardous waste landfill sites in England.

Few studies have investigated the occurrence of both low birth weight (LBW) and congenital anomalies in populations living near hazardous waste landfill sites. The authors investigated the risk of LBW near 10 English hazardous waste landfill sites included in a previous European study, which reported an increased risk of congenital anomalies. Odds ratios, adjusted for sex, deprivation, year of birth, and study area (pooled ORs), were estimated for LBW (< 2500 gm) within 0-3 km compared with 3-7 km zones around the landfill sites. The authors found a small and not statistically significant increase in risk of LBW (OR = 1.03, 95% confidence interval = 0.98-1.08) within 3 km of hazardous waste landfill sites. Their findings suggest that previously reported results for congenital anomalies should not be extrapolated to a wider range of pregnancy outcomes but should be evaluated separately for each.

Congenital Abnormalities↗

PubMed2003

The impact of environmental pollution on congenital anomalies.

Major congenital anomalies are diagnosed in 2-4% of births. In this paper we review epidemiological studies that have specifically looked at congenital anomalies as a possible outcome of community exposure to chemical exposures associated with environmental pollution. These include studies of drinking water contaminants (heavy metals and nitrates, chlorinated and aromatic solvents, and chlorination by-products), residence near waste disposal sites and contaminated land, pesticide exposure in agricultural areas, air pollution and industrial pollution sources, food contamination, and disasters involving accidental, negligent or deliberate chemical releases of great magnitude. We conclude that there are relatively few environmental pollution exposures for which we can draw strong conclusions about the potential to cause congenital anomalies and, if so, the chemical constituents implicated, to provide an evidence base for public health and clinical practice. A precautionary approach should be adopted at both community and individual level. In order to prevent congenital anomalies, one must reduce exposure to potential teratogens before pregnancy is recognized (i.e. preconceptionally and in the first few weeks of pregnancy). It is a challenge to develop effective strategies for preconceptional care within the primary care framework. Prenatal service providers and counsellors need to be aware of the uncertainties regarding environmental pollution when addressing parental concerns.

Air Pollution↗

PubMed2002

A job-exposure matrix for potential endocrine-disrupting chemicals developed for a study into the association between maternal occupational exposure and hypospadias.

A study to assess the association between the prevalence of hypospadias and maternal occupational exposure to potential endocrine-disrupting chemicals was carried out using data from the congenital anomaly register of the Office for National Statistics. The occupation of the mother is recorded in this register and to facilitate the assessment of maternal occupational exposure, a specific job-exposure matrix for potential endocrine-disrupting chemicals was developed. Seven categories of contaminants were evaluated (pesticides, polychlorinated organic compounds, phthalates, alkylphenolic compounds, bi-phenolic compounds, heavy metals and other substances). Maternal occupations were all coded using the 1980 version of Categories of Occupations. Three occupational hygienists assessed the likelihood of exposure (unlikely, possible, probable) to these seven substance groups for all 348 possible job titles independently. Almost 30% of the job titles were classified as exposed to at least one substance category (possible or probable), with approximately 16% of the job titles being probably exposed to at least one substance category. Some examples of occupations with probable exposure to potential endocrine-disrupting chemicals include: farm workers, electricians, workers in the plastics industry, painters, printers, hairdressers, dental practitioners, laboratory workers, textile workers and cleaners. It is recognized that there are a lot of limitations to the use of job-exposure matrices in general and with the matrix presented in this paper in particular. However, the matrix forms the basis on which further developments on occupational exposure assessment of potential endocrine-disrupting chemicals could be founded. In addition, the job-exposure matrix has identified areas where more exposure information is required. For example, exposure to potential endocrine-disrupting chemicals can occur in occupations such as hairdressing and workers in beauty salons, where the working population is more likely to be female and for which little data exist on levels of exposure.

Adult↗