A5053984915- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pediatric health and respiratory diseases
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Asthma and respiratory diseases
- Air Quality and Health Impacts
- Neonatal Respiratory Health Research
- COVID-19 and Mental Health
- Climate Change and Health Impacts
- Genetic and phenotypic traits in livestock
- Metabolomics and Mass Spectrometry Studies
- Employment and Welfare Studies
- COVID-19 Impact on Reproduction
- Cancer-related gene regulation
- Energy and Environment Impacts
- Liver Disease Diagnosis and Treatment
- Neuroscience of respiration and sleep
- Respiratory viral infections research
- Workplace Health and Well-being
- COVID-19 and healthcare impacts
- IL-33, ST2, and ILC Pathways
- Hypothalamic control of reproductive hormones
- Birth, Development, and Health
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Obstructive Sleep Apnea Research
Imperial College London
2019-2025
Lung Institute
2021-2023
University Medical Center Groningen
2015-2020
University of Groningen
2015-2020
Délégation Paris 7
2018-2020
Inserm
2018-2020
Université Paris Cité
2018-2020
Institute for Asthma and Allergy
2018
Abstract Background With genome-wide association data for many exposures and outcomes now available from large biobanks, one-sample Mendelian randomization (MR) is increasingly used to investigate causal relationships. Many robust MR methods are address pleiotropy, but these assume independence between the gene-exposure gene-outcome estimates. Unlike in two-sample MR, two estimates obtained same individuals, assumption of does not hold presence confounding. Methods simulations mimicking a...
Background: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain association. Objectives: Our main aim was to study between long-term and methylation. Methods: We performed a genome-wide using robust linear regression models in 1,017 subjects from LifeLines cohort analyze nitrogen dioxide ( NO2) particulate matter PM2.5, fine aerodynamic diameter ≤2.5μm; PM10,...
Objectives Occupational pesticide exposure is associated with a wide range of diseases, including lung but it largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational to and genome-wide methylation sites. Methods 1561 subjects LifeLines were included either no (n=1392), low (n=108) or high (n=61) any type (estimated based on current last...
Background Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk adult possibly due to residual confounding. To overcome issues confounding, we used Mendelian randomisation (MR), i.e., genetic variants were as instrumental variables estimate causal effects post-pubertal asthma both females males. Methods findings MR analyses UK Biobank 243,316 women using 254 for age...
Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) pre-bronchodilation and its change in adults. In a discovery–replication EWAS design, blood spirometry were measured twice, 6–15 years apart, the same participants of three adult population-based discovery cohorts (n=2043). Associated markers...
To quantify occupational risks of COVID-19 among healthcare staff during the first wave (9 March 2020-31 July 2020) pandemic in England.We used pseudonymised data on 902 813 individuals employed by 191 National Health Service trusts to explore demographic and risk factors for sickness absence ascribed (n=92 880). We estimated ORs multivariable logistic regression.With adjustment employing trust, characteristics previous frequency absence, relative administrative/clerical occupations was...
Genetic and environmental factors play a role in the development of COPD. The epigenome, more specifically DNA methylation, is recognized as important link between these factors. We postulate that methylation one routes by which cigarette smoke influences In this study, we aim to identify CpG-sites are associated with exposure lung function levels whole blood validate tissue. association pack years was studied genome-wide 658 current smokers >5 using robust linear regression analysis. Using...
Associations of low lung function with features poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors.We performed three analyses: (1) to association tests in Northern Finland Birth cohort 1966, (2) cross-trait linkage disequilibrium score regression (LDSC) compare backgrounds and (3) Mendelian randomisation (MR) analysis assess the effect traits...
Background Vitamin A, an essential micronutrient obtained through the diet, plays a crucial role in lung development and contributes to regeneration. We aimed investigate its effect on adult function using triangulation of evidence from both observational genetic data. Methods Using data 150 000 individuals UK Biobank correcting for measurement error (generalised structural equation modelling), we first investigated association dietary vitamin A intake (total carotene retinol) with (forced...
Abstract Background With genome-wide association data for many exposures and outcomes now available from large biobanks, one-sample Mendelian randomization (MR) is increasingly used to investigate causal relationships. Many robust MR methods are address pleiotropy, but these assume independence between the gene-exposure gene-outcome estimates. Unlike in two-sample MR, two estimates obtained same individuals, assumption of does not hold presence confounding. Methods simulations mimicking a...
In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association causal. We therefore used Mendelian randomisation (MR) approach, which affected by classical confounding, to assess the effect age at natural on lung function.We included 94 742 naturally post-menopausal women from UK Biobank performed MR analyses expiratory volume in 1 s (FEV1),...
Background The prevalence of obstructive sleep apnea is higher in women after menopause. This suggested to be a result an altered sex hormone balance but has so far not been confirmed population-based study. Objective To investigate whether serum concentration estrogens and progesterone are associated with the symptoms middle-aged general population. Methods We analyzed data from 774 (40–67 years) 15 study centers seven countries participating second follow-up European Community Respiratory...
Chronic obstructive pulmonary disease (COPD) is a major health burden in adults and cigarette smoking considered the most important environmental risk factor of COPD. Chromosome 15q25.1 locus associated with both COPD smoking. Our study aims at understanding mechanism underlying association chromosome through epigenetic transcriptional variation population-based setting. To assess if COPD-associated variants are methylation quantitative trait loci, epigenome-wide analysis four genetic...
Higher levels of testosterone have been associated with better lung function in cross-sectional population-based studies. The role women and decline men or is unclear. We studied 5114 5467 the UK Biobank high-quality spirometry at baseline (2006–2010) 8.4 years later. associations total (TT), calculated free (cFT), androgen index (FAI) sex hormone-binding globulin (SHBG) forced expiratory volume 1 s (FEV ), vital capacity (FVC) FEV /FVC using linear regression markers mixed-effects...
To explore the patterns of sickness absence in National Health Service (NHS) staff attributable to mental ill health during first wave COVID-19 epidemic March-July 2020.Case-referent analysis a secondary dataset.NHS Trusts England.Pseudonymised data on 959 356 employees who were continuously employed by NHS trusts 1 January 2019 31 July 2020.Trends burden due from 2020 according demographic, regional and occupational characteristics.Over study period, 164 202 new episodes for recorded 12.5%...
Background Observational studies suggest that total testosterone (TT) and sex hormone-binding globulin (SHBG) may have beneficial effects on lung function, but these findings might be spurious due to confounding reverse causation. We addressed limitations by using multivariable Mendelian randomisation (MVMR) investigate the independent causal of TT SHBG function. Methods first identified genetic instruments performing genome-wide association analyses in large UK Biobank, separately males...
Chronic obstructive pulmonary disease (COPD) is among the major health burdens in adults. While cigarette smoking leading risk factor, a growing number of genetic variations have been discovered to influence susceptibility. Epigenetic modifications may mediate response genome and regulate gene expression. Chromosome 19q13.2 region associated with both COPD, yet its functional role unclear. Our study aimed determine whether rs7937 (RAB4B, EGLN2), top variant identified genome-wide association...
Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette associated with differential DNA methylation in whole blood. So far, it unclear whether epigenetics also role subjects COPD who never smoked. Therefore, we aimed to identify lung function smokers.We determined epigenome-wide levels of 396,243 CpG-sites (Illumina 450 K) blood smokers four independent cohorts, LifeLines COPD&C (N = 903), DEEP 166), Rotterdam Study (RS)-III 150) and...
Abstract Background Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well systemic changes. Metabolic changes in blood may help detect COPD an earlier stage predict prognosis. Methods We conducted comprehensive study of circulating metabolites, measured proton Nuclear Magnetic Resonance Spectroscopy, relation with function. The discovery sample consisted 5557 individuals from two large population-based...