Lifelines COVID-19 cohort: investigating COVID-19 infection and its health and societal impacts in a Dutch population-based cohort.

Purpose: The Lifelines COVID-19 cohort was set up to assess the psychological and societal impacts of the COVID-19 pandemic and investigate potential risk factors for COVID-19 within the Lifelines prospective population cohort.

Participants: Participants were recruited from the 140 000 eligible participants of Lifelines and the Lifelines NEXT birth cohort, who are all residents of the three northern provinces of the Netherlands. Participants filled out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March 2020, and the cohort consists of everyone who filled in at least one questionnaire in the first 8 weeks of the project.

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

Background: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.

Objective: We sought to identify DNA methylation profiles associated with childhood allergy.

Methods: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design.

Lifelines NEXT: a prospective birth cohort adding the next generation to the three-generation Lifelines cohort study.

Epidemiological research has shown there to be a strong relationship between preconceptional, prenatal, birth and early-life factors and lifelong health. The Lifelines NEXT is a birth cohort designed to study the effects of intrinsic and extrinsic determinants on health and disease in a four-generation design. It is embedded within the Lifelines cohort study, a prospective three-generation population-based cohort study recording the health and health-related aspects of 167,729 individuals living in Northern Netherlands.

Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome.

Changes in the gut microbiota have been associated with two of the most common gastrointestinal diseases, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Here, we performed a case-control analysis using shotgun metagenomic sequencing of stool samples from 1792 individuals with IBD and IBS compared with control individuals in the general population. Despite substantial overlap between the gut microbiome of patients with IBD and IBS compared with control individuals, we were able to use gut microbiota composition differences to distinguish patients with IBD from those with IBS.

Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles.

Several gastrointestinal diseases show a sex imbalance, although the underlying (patho)physiological mechanisms behind this are not well understood. The gut microbiome may be involved in this process, forming a complex interaction with host immune system, sex hormones, medication and other environmental factors. Here we performed sex-specific analyses of fecal microbiota composition in 1135 individuals from a population-based cohort.

DNA methylation in childhood asthma: an epigenome-wide meta-analysis.

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma.

Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project.

The emerging landscape of dynamic DNA methylation in early childhood.

Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood.

Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p < 1.14 × 10.

The effect of host genetics on the gut microbiome.

The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 × 10.

Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.

Background: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.

Objectives: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.

Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity.

Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition.

DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis.

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role.

Proton pump inhibitors affect the gut microbiome.

Background And Aims: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens.

DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring.

Background: We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood.

Methods: First, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip.

Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants.

Background: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD.