Publications by authors named "Medea Imboden"

104 Publications

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Genome Biol 2021 06 29;22(1):194. Epub 2021 Jun 29.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

Results: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243879PMC
June 2021

Variants associated with expression have sex-differential effects on lung function.

Wellcome Open Res 2020 24;5:111. Epub 2021 May 24.

Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU, UK.

Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 ) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV ) (P=3.15x10 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV more in males (untransformed FEV β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( ) gene and was previously associated with lung function and lung expression. We found expression was significantly different between the sexes (P=6.90x10 ), but we could not detect sex differential effects of rs7697189 on expression. We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the gene. Establishing the mechanism by which SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/wellcomeopenres.15846.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938335.2PMC
May 2021

Causal Effects of Body Mass Index on Airflow Obstruction and Forced Mid-Expiratory Flow: A Mendelian Randomization Study Taking Interactions and Age-Specific Instruments Into Consideration Toward a Life Course Perspective.

Front Public Health 2021 11;9:584955. Epub 2021 May 11.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18-60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25-75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25-75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25-75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.584955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144328PMC
June 2021

Perceived built environment, health-related quality of life and health care utilization.

PLoS One 2021 6;16(5):e0251251. Epub 2021 May 6.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Previous research has shown that the built environment plays a crucial role for health-related quality of life (HRQoL) and health care utilization. But, there is limited evidence on the independence of this association from lifestyle and social environment. The objective of this cross-sectional study was to investigate these associations, independent of the social environment, physical activity and body mass index (BMI). We used data from the third follow-up of the Swiss study on Air Pollution and Lung and Heart diseases In Adults (SAPALDIA), a population based cohort with associated biobank. Covariate adjusted multiple quantile and polytomous logistic regressions were performed to test associations of variables describing the perceived built environment with HRQoL and health care utilization. Higher HRQoL and less health care utilization were associated with less reported transportation noise annoyance. Higher HRQoL was also associated with greater satisfaction with the living environment and more perceived access to greenspaces. These results were independent of the social environment (living alone and social engagement) and lifestyle (physical activity level and BMI). This study provides further evidence that the built environment should be designed to integrate living and green spaces but separate living and traffic spaces in order to improve health and wellbeing and potentially save health care costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251251PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101743PMC
May 2021

Short-term personal and outdoor exposure to ultrafine and fine particulate air pollution in association with blood pressure and lung function in healthy adults.

Environ Res 2021 03 4;194:110579. Epub 2020 Dec 4.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands; Julius Center, University Medical Center Utrecht, Utrecht, the Netherlands.

Studies reporting on associations between short-term exposure to outdoor fine (PM), and ultrafine particles (UFP) and blood pressure and lung function have been inconsistent. Few studies have characterized exposure by personal monitoring, which especially for UFP may have resulted in substantial exposure measurement error. We investigated the association between 24-h average personal UFP, PM, and soot exposure and dose and the health parameters blood pressure and lung function. We further assessed the short-term associations between outdoor concentrations measured at a central monitoring site and near the residences and these health outcomes. We performed three 24-h personal exposure measurements for UFP, PM, and soot in 132 healthy adults from Basel (Switzerland), Amsterdam and Utrecht (the Netherlands), and Turin (Italy). Monitoring of each subject was conducted in different seasons in a one-year study period. Subject's activity levels and associated ventilation rates were measured using actigraphy to calculate the inhaled dose. After each 24-h monitoring session, blood pressure and lung function were measured. Contemporaneously with personal measurements, UFP, PM and soot were measured outdoor at the subject's residential address and at a central site in the research area. Associations between short-term personal and outdoor exposure and dose to UFP, PM, and soot and health outcomes were tested using linear mixed effect models. The 24-h mean personal, residential and central site outdoor UFP exposures were not associated with blood pressure or lung function. UFP mean exposures in the 2-h prior to the health test was also not associated with blood pressure and lung function. Personal, central site and residential PM exposure were positively associated with systolic blood pressure (about 1.4 mmHg increase per Interquartile range). Personal soot exposure and dose were positively associated with diastolic blood pressure (1.2 and 0.9 mmHg increase per Interquartile range). No consistent associations between PM or soot exposure and lung function were observed. Short-term personal, residential outdoor or central site exposure to UFP was not associated with blood pressure or lung function. Short-term personal PM and soot exposures were associated with blood pressure, but not lung function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2020.110579DOI Listing
March 2021

Corona Immunitas: study protocol of a nationwide program of SARS-CoV-2 seroprevalence and seroepidemiologic studies in Switzerland.

Int J Public Health 2020 Dec 24;65(9):1529-1548. Epub 2020 Oct 24.

Unit of Population Epidemiology, Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.

Objectives: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community.

Methods: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic.

Results: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far.

Conclusions: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00038-020-01494-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584867PMC
December 2020

The modifying role of physical activity in the cross-sectional and longitudinal association of health-related quality of life with physiological functioning-based latent classes and metabolic syndrome.

Health Qual Life Outcomes 2020 Oct 20;18(1):345. Epub 2020 Oct 20.

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051, Basel, CH, Switzerland.

Background: Single cardio-metabolic risk factors are each known modifiable risk factors for adverse health and quality of life outcomes. Yet, evidence on the clustered effect of these parameters and the metabolic syndrome (MetS) on health-related quality of life (HRQoL) is still limited and mostly cross-sectional. The objectives of this study were to identify clusters of cardio-metabolic physiological functioning, to assess their associations with HRQoL in comparison with the MetS, to elucidate the modifying role of physical activity, and to assess differences in health service utilization.

Methods: This study is based on longitudinal data from two time points (2010/11 & 2017/18) of the Swiss Study on Air Pollution and Lung and Heart Diseases (SAPALDIA). Latent class analysis (LCA) grouped participants based on a priori selected cardio-metabolic and MetS related physiological functioning variables (Body mass index, body fat, glycated hemoglobin, blood triglycerides, blood pressure). The 36-item Short-Form Health Survey (SF-36) was used to assess HRQoL. Quantile regressions were performed with and without adjustment for physical activity, to detect independent associations of the latent classes, MetS and physical activity with HRQoL. To assess the modifying role of physical activity, we additionally grouped participants based on the combination of physical activity and latent classes or MetS, respectively. Logistic regressions were used to investigate health service utilization as outcome.

Results: The LCA resulted in three classes labeled "Healthy" (30% of participants in 2017/18), "At risk" and "Unhealthy" (29%). The Unhealthy class scored lowest in all physical component scores of HRQoL. Compared to healthy and active participants, inactive participants in the "Unhealthy" class showed lower scores in the physical functioning domain both cross-sectionally (- 9.10 (- 12.02; - 6.18)) and longitudinally. This group had an odds ratio of 2.69 (1.52; 4.74) for being hospitalized in the previous 12 months.

Conclusions: These results point to subjects with adverse cardio-metabolic physiological functioning and low activity levels as an important target group for health promotion and maintenance of well-being. The promotion of physical activity at the early stages of aging seems pivotal to mitigate the impact of the MetS on HRQoL at higher age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12955-020-01557-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574351PMC
October 2020

Dental and periodontal health in a Swiss population-based sample of older adults: a cross-sectional study.

Eur J Oral Sci 2020 12 18;128(6):508-517. Epub 2020 Oct 18.

Department of Reconstructive Dentistry, University Center for Dental Medicine, University of Basel, Basel, Switzerland.

In this cross-sectional study, the prevalences of tooth loss, prosthetic dental restorations, and probing pocket depths (PPD) ≥4 mm, and their relationship to sociodemographic factors, were investigated in older Swiss adults. There were up to 1,673 participants aged ≥55 yr in the fourth survey of the Swiss Cohort Study on Air Pollution And Lung And Heart Disease In Adults (SAPALDIA4). Missing teeth, prosthetic dental restorations, and PPD ≥4 mm were recorded in clinical examinations conducted by field workers and compared with self-reported information from questionnaires. Examination data showed that participants were missing five teeth on average, 74.8% had a prosthetic dental restoration, and 21.1% had PPD of ≥4 mm. The mean number of missing teeth and the prevalences of tooth loss, fixed dental prostheses, and removable dental prostheses were associated with age, education level, smoking status, and time since last visit to a dentist. Comparison of data obtained by field workers and that from self-reports show a high level of agreement for the number of missing teeth and the prevalence of removable dental prostheses, but a lower level of agreement for self-reports of fixed dental prostheses and periodontitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eos.12738DOI Listing
December 2020

Incidence of depression in relation to transportation noise exposure and noise annoyance in the SAPALDIA study.

Environ Int 2020 11 4;144:106014. Epub 2020 Aug 4.

Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.

Prospective evidence on the risk of depression in relation to transportation noise exposure and noise annoyance is limited and mixed. We aimed to investigate the associations of long-term exposure to source-specific transportation noise and noise annoyance with incidence of depression in the SAPALDIA (Swiss cohort study on air pollution and lung and heart diseases in adults) cohort. We investigated 4,581 SAPALDIA participants without depression in the year 2001/2002. Corresponding one-year mean road, railway and aircraft day-evening-night noise (Lden) was calculated at the most exposed façade of the participants' residential floors, and transportation noise annoyance was assessed on an 11-point scale. Incident cases of depression were identified in 2010/2011, and comprised participants reporting physician diagnosis, intake of antidepressant medication or having a short form-36 mental health score < 50. We used robust Poisson regressions to estimate the mutually adjusted relative risks (RR) and 95% confidence intervals (CI) of depression, independent of traffic-related air pollution and other potential confounders. Incidence of depression was 11 cases per 1,000 person-years. In single exposure models, we observed positive but in part, statistically non-significant associations (per 10 dB) of road traffic Lden [RR: 1.06 (0.93, 1.22)] and aircraft Lden [RR: 1.19 (0.93, 1.53)], and (per 1-point difference) of noise annoyance [RR: 1.05 (1.02, 1.08)] with depression risk. In multi-exposure model, noise annoyance effect remained unchanged, with weaker effects of road traffic Lden [(RR: 1.02 (0.89, 1.17)] and aircraft Lden [(RR: 1.17 (0.90, 1.50)]. However, there were statistically significant indirect effects of road traffic Lden [(β: 0.02 (0.01, 0.03)] and aircraft Lden [β: 0.01 (0.002, 0.02)] via noise annoyance. There were no associations with railway Lden in the single and multi-exposure models [(RR: 0.88 (0.75, 1.03)]. We made similar findings among 2,885 non-movers, where the effect modification and cumulative risks were more distinct. Noise annoyance effect in non-movers was stronger among the insufficiently active (RR: 1.09; 95%CI: 1.02, 1.17; p = 0.07) and those with daytime sleepiness [RR: 1.07 (1.02, 1.12); p = 0.008]. Cumulative risks of Lden in non-movers showed additive tendencies for the linear cumulative risk [(RR: 1.31 (0.90, 1.91)] and the categorical cumulative risk [(RR: 2.29 (1.02, 5.14)], and remained stable to noise annoyance. Transportation noise level and noise annoyance may jointly and independently influence the risk of depression. Combined long-term exposures to noise level seems to be most detrimental, largely acting via annoyance. The moderation of noise annoyance effect by daytime sleepiness and physical activity further contribute to clarifying the involved mechanisms. More evidence is needed to confirm these findings for effective public health control of depression and noise exposure burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.106014DOI Listing
November 2020

The independent association of source-specific transportation noise exposure, noise annoyance and noise sensitivity with health-related quality of life.

Environ Int 2020 10 15;143:105960. Epub 2020 Jul 15.

Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

Noise exposure is affecting health-related quality of life (HRQoL). There are many modelling approaches linking specific noise sources with single health-related outcomes. However, an integrated approach is missing taking into account measured levels as well as noise annoyance and sensitivity and assessing their independent association with HRQoL domains. Therefore, we investigated the predictive association of most common transportation noise sources (aircraft, railway and road traffic) as well as transportation noise annoyance and noise sensitivity with HRQoL using data from SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We assessed 2035 subjects, who participated in the second and third wave of SAPALDIA (3&4) and had complete information on exposure, outcome and covariates. At SAPALDIA3, we calculated annual means (Lden) of source-specific transportation noise exposure at the most exposed facade of participant's dwelling floor height. Participants reported noise annoyance on the widely used 11-point ICBEN scale and answered to 10 questions assessing individual noise sensitivity. To assess the potentially predictive effect of these noise exposures, HRQoL was assessed about 8 years later (SAPALDIA4) using the SF-36. We performed predictive multiple quantile regression models to elucidate associations of noise parameters measured at SAPALDIA3 with median SF-36 scores at SAPALDIA4. Source-specific transportation noise exposures showed few yet not consistent associations with HRQoL scores. We observed statistically significant negative associations of transportation noise annoyance with HRQoL scores covering mental health components (adjusted difference in SF-36 mental health score between highest vs. lowest annoyance tertile: -2.54 (95%CI: -3.89; -1.20). Noise sensitivity showed strongest and most consistent associations with HRQoL scores covering both general and mental health components (adjusted difference in SF-36 scores between highest vs. lowest sensitivity tertile: Mental health -5.96 (-7.57; -4.36); general health -5.16 (-7.08; -3.24)). Within all noise parameters, we predominantly observed negative associations of noise sensitivity with HRQoL attaining a magnitude of potential clinical relevance. This implies that factors other than transportation noise exposure may be relevant for this exposure-outcome relation. Nonetheless, transportation noise annoyance showed relevant associations with mental health components, indicating a negative association of transportation noise with HRQoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.105960DOI Listing
October 2020

Patterns of cross-sectional and predictive physical activity in Swiss adults aged 52+: results from the SAPALDIA cohort.

Swiss Med Wkly 2020 Jun 18;150:w20266. Epub 2020 Jun 18.

Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Switzerland.

Background: Non-communicable diseases (NCDs) account for the vast majority of deaths in Switzerland. Insufficient physical activity (PA) is an established NCD risk factor and PA is known to be beneficial for physical and mental wellbeing. Sedentary behaviour (SB) is an additional, independent risk factor and associated with frailty in older adults. This study aimed at describing cross-sectional PA patterns in a general population sample of subjects aged 52 years and older (52+) from eight areas across different language regions of Switzerland. Additionally, the predictive association of self-reported PA for objectively measured PA was tested.

Methods: Participants 52+ of the Swiss Cohort Study on Air Pollution And Lung and Heart Disease In Adults (SAPALDIA) who completed accelerometer data collection at the most recent follow-up (SAPALDIA4 in 2017/18) and provided information on determinants of interest (sex, age, body mass index [BMI], language region, education, employment status, civil status, smoking) were included in the analysis (n = 1314). The accelerometer-derived average time spent in different PA intensities (SB, light PA [LPA], moderate-to-vigorous PA [MVPA]) was estimated according to participant characteristics with control for season and wear time using multiple linear regressions. In further analyses, the predictive effect of changes in self-reported PA over roughly ten years between SAPALDIA2 (2001/02) and SAPALDIA3 (2010/11) (remaining inactive [RI]; becoming inactive [BI]; becoming active [BA]; remaining active [RA]) on the objectively measured SB, LPA and MVPA obtained seven years later by accelerometry (SAPALDIA4), was assessed using multiple linear regression models.

Results: Overall, 21.7% of 52+ participants met the Swiss recommendations for subjectively assessed PA. Obese participants, 75+ year-olds, smokers and subjects living alone spent more time in SB and less time in LPA and MVPA compared with participants with a BMI below 25 kg/m2, between 52 and 64 years old, not smoking and being married, respectively. Residents living in the French-speaking part of Switzerland were less likely to engage in MVPA compared with residents from the German-speaking part and thus were less likely to meet the PA recommendations. A trend for increasing PA and decreasing SB was observed consistently across the four groups (RI, BI, BA, RA) of predictive self-reported PA patterns with participants remaining active over the course of roughly ten years showing highest levels of PA and lowest levels of SB measured objectively at SAPALDIA4.

Conclusion: The high proportion of SB points to the need of physical activity promotion for the older part of the population in Switzerland. According to our data, behavioural changes in PA are possible and sustainable as we can see in the group of participants becoming active and this is essential for health promotion recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4414/smw.2020.20266DOI Listing
June 2020

Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study.

BMC Pulm Med 2020 Jun 16;20(1):171. Epub 2020 Jun 16.

National Heart and Lung Institute, Imperial College London, London, UK.

Background: Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation.

Methods: We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV, FVC, and FEV/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2.

Results: In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs.

Conclusions: To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-020-01212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298775PMC
June 2020

Regular Physical Activity Levels and Incidence of Restrictive Spirometry Pattern: A Longitudinal Analysis of 2 Population-Based Cohorts.

Am J Epidemiol 2020 12;189(12):1521-1528

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwaa087DOI Listing
December 2020

Genome-Wide DNA Methylation in Peripheral Blood and Long-Term Exposure to Source-Specific Transportation Noise and Air Pollution: The SAPALDIA Study.

Environ Health Perspect 2020 06 1;128(6):67003. Epub 2020 Jun 1.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Few epigenome-wide association studies (EWAS) on air pollutants exist, and none have been done on transportation noise exposures, which also contribute to environmental burden of disease.

Objective: We performed mutually independent EWAS on transportation noise and air pollution exposures.

Methods: We used data from two time points of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) from 1,389 participants contributing 2,542 observations. We applied multiexposure linear mixed-effects regressions with participant-level random intercept to identify significant Cytosine-phosphate-Guanine (CpG) sites and differentially methylated regions (DMRs) in relation to 1-y average aircraft, railway, and road traffic day-evening-night noise (Lden); nitrogen dioxide (); and particulate matter (PM) with aerodynamic diameter (). We performed candidate (CpG-based; cross-systemic phenotypes, combined into "allostatic load") and agnostic (DMR-based) pathway enrichment tests, and replicated previously reported air pollution EWAS signals.

Results: We found no statistically significant CpGs at false discovery rate . However, 14, 48, 183, 8, and 71 DMRs independently associated with aircraft, railway, and road traffic Lden; ; and , respectively, with minimally overlapping signals. Transportation Lden and air pollutants tendentially associated with decreased and increased methylation, respectively. We observed significant enrichment of candidate DNA methylation related to C-reactive protein and body mass index (aircraft, road traffic Lden, and ), renal function and "allostatic load" (all exposures). Agnostic functional networks related to cellular immunity, gene expression, cell growth/proliferation, cardiovascular, auditory, embryonic, and neurological systems development were enriched. We replicated increased methylation in cg08500171 () and decreased methylation in cg17629796 ().

Conclusions: Mutually independent DNA methylation was associated with source-specific transportation noise and air pollution exposures, with distinct and shared enrichments for pathways related to inflammation, cellular development, and immune responses. These findings contribute in clarifying the pathways linking these exposures and age-related diseases but need further confirmation in the context of mediation analyses. https://doi.org/10.1289/EHP6174.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/EHP6174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263738PMC
June 2020

Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study.

Eur Respir J 2020 09 3;56(3). Epub 2020 Sep 3.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, Research Triangle Park, NC, USA

Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma; however, studies in adults are rare and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study (EWAS) of blood DNA methylation in adults in relation to non-atopic and atopic asthma.We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a United States agricultural cohort. Atopy was defined by serum specific immunoglobulin E (IgE). Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression.No associations were observed with atopy without asthma. Numerous cytosine-phosphate-guanine (CpG) sites were differentially methylated in non-atopic asthma (eight at family-wise error rate (FWER) p<9×10, 524 at false discovery rate (FDR) less than 0.05) and implicated 382 novel genes. More CpG sites were identified in atopic asthma (181 at FWER, 1086 at FDR) and implicated 569 novel genes. 104 FDR CpG sites overlapped. 35% of CpG sites in non-atopic asthma and 91% in atopic asthma replicated in studies of whole blood, eosinophils, airway epithelium, or nasal epithelium. Implicated genes were enriched in pathways related to the nervous system or inflammation.We identified numerous, distinct differentially methylated CpG sites in non-atopic and atopic asthma. Many CpG sites from blood replicated in asthma-relevant tissues. These circulating biomarkers reflect risk and sequelae of disease, as well as implicate novel genes associated with non-atopic and atopic asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00217-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469973PMC
September 2020

microRNA expression profiles and personal monitoring of exposure to particulate matter.

Environ Pollut 2020 Aug 18;263(Pt B):114392. Epub 2020 Mar 18.

Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, 10060 Candiolo, Turin, Italy. Electronic address:

An increasing number of findings from epidemiological studies support associations between exposure to air pollution and the onset of several diseases, including pulmonary, cardiovascular and neurodegenerative diseases, and malignancies. However, intermediate, and potentially mediating, biological mechanisms associated with exposure to air pollutants are largely unknown. Previous studies on the human exposome have shown that the expression of certain circulating microRNAs (miRNAs), regulators of gene expression, are altered upon exposure to traffic-related air pollutants. In the present study, we investigated the relationship between particulate matter (PM) smaller than 2.5 μm (PM), PM absorbance (as a proxy of black carbon and soot), and ultrafine-particles (UFP, smaller than 0.1 μm), measured in healthy volunteers by 24 h personal monitoring (PEM) sessions and global expression levels of peripheral blood miRNAs. The PEM sessions were conducted in four European countries, namely Switzerland (Basel), United Kingdom (Norwich), Italy (Turin), and The Netherlands (Utrecht). miRNAs expression levels were analysed using microarray technology on blood samples from 143 participants. Seven miRNAs, hsa-miR-24-3p, hsa-miR-4454, hsa-miR-4763-3p, hsa-miR-425-5p, hsa-let-7d-5p, hsa-miR-502-5p, and hsa-miR-505-3p were significantly (FDR corrected) expressed in association with PM personal exposure, while no significant association was found between miRNA expression and the other pollutants. The results obtained from this investigation suggest that personal exposure to PM is associated with miRNA expression levels, showing the potential for these circulating miRNAs as novel biomarkers for air pollution health risk assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.114392DOI Listing
August 2020

The haemochromatosis gene Hfe and Kupffer cells control LDL cholesterol homeostasis and impact on atherosclerosis development.

Eur Heart J 2020 10;41(40):3949-3959

Department of Cardiac Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria.

Aims: Imbalances of iron metabolism have been linked to the development of atherosclerosis. However, subjects with hereditary haemochromatosis have a lower prevalence of cardiovascular disease. The aim of our study was to understand the underlying mechanisms by combining data from genome-wide association study analyses in humans, CRISPR/Cas9 genome editing, and loss-of-function studies in mice.

Methods And Results: Our analysis of the Global Lipids Genetics Consortium (GLGC) dataset revealed that single nucleotide polymorphisms (SNPs) in the haemochromatosis gene HFE associate with reduced low-density lipoprotein cholesterol (LDL-C) in human plasma. The LDL-C lowering effect could be phenocopied in dyslipidaemic ApoE-/- mice lacking Hfe, which translated into reduced atherosclerosis burden. Mechanistically, we identified HFE as a negative regulator of LDL receptor expression in hepatocytes. Moreover, we uncovered liver-resident Kupffer cells (KCs) as central players in cholesterol homeostasis as they were found to acquire and transfer LDL-derived cholesterol to hepatocytes in an Abca1-dependent fashion, which is controlled by iron availability.

Conclusion: Our results disentangle novel regulatory interactions between iron metabolism, KC biology and cholesterol homeostasis which are promising targets for treating dyslipidaemia but also provide a mechanistic explanation for reduced cardiovascular morbidity in subjects with haemochromatosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa140DOI Listing
October 2020

Incidence trends of airflow obstruction among European adults without asthma: a 20-year cohort study.

Sci Rep 2020 02 26;10(1):3452. Epub 2020 Feb 26.

Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, UK.

Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AO), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AO was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AO incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AO incidence is expected to be half of AO incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-60478-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044325PMC
February 2020

Association of adult lung function with accelerated biological aging.

Aging (Albany NY) 2020 01 11;12(1):518-542. Epub 2020 Jan 11.

Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10; Intrinsic Epigenetic AA:P-value=2x10) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity). Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.102639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977706PMC
January 2020

Asymptomatic Plasmodium infection and glycemic control in adults: Results from a population-based survey in south-central Côte d'Ivoire.

Diabetes Res Clin Pract 2019 Oct 11;156:107845. Epub 2019 Sep 11.

Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.

Aims: We investigated the cross-sectional associations of Plasmodium infection (PI) with fasting glucose (FG) and glycated hemoglobin (HbA1c) in malaria-endemic south-central Côte d'Ivoire.

Methods: We studied 979 participants (non-pregnant; no treated diabetes; 51% males; 18-87 years) of the Côte d'Ivoire Dual Burden of Disease study. Fasting venous blood was obtained for PI, FG, and HbA1c assessment. We defined PI as a positive malaria rapid diagnostic test (RDT) or microscopic identification of Plasmodium species. We applied multivariable linear regressions to assess beta coefficients (β) and 95% confidence intervals (CIs) of PI positivity for FG and HbA1c independent of diabetes risk factors.

Results: Prevalence of PI was 10.1% (5.5% microscopy; 9.7% RDT) without clinical fever. Prevalence of FG-based prediabetes (45.8%) and diabetes (3.6%) were considerably higher than HbA1c-based values (2.7% and 0.7%, respectively). PI was independently associated with FG among participants with higher body temperature (β 0.34, 95% CI 0.06-0.63, p = 0.028), or family history of diabetes (β 0.88, 95% CI 0.28-1.47, p = 0.009). Similar patterns observed with HbA1c were obliterated on accounting for FG. We also observed consistent associations with parasite density.

Conclusions: FG-based diabetes diagnosis in the presence of asymptomatic PI may misclassify or overestimate diabetes burden in malaria-endemic settings. Longitudinal studies are needed to confirm these findings and determine the risk for diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2019.107845DOI Listing
October 2019

The mediating effect of immune markers on the association between ambient air pollution and adult-onset asthma.

Sci Rep 2019 06 19;9(1):8818. Epub 2019 Jun 19.

Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, 3584 CM, Utrecht, the Netherlands.

We aim to investigate to what extent a set of immune markers mediate the association between air pollution and adult-onset asthma. We considered long-term exposure to multiple air pollution markers and a panel of 13 immune markers in peripheral blood samples collected from 140 adult cases and 199 controls using a nested-case control design. We tested associations between air pollutants and immune markers and adult-onset asthma using mixed-effects (logistic) regression models, adjusted for confounding variables. In order to evaluate a possible mediating effect of the full set of immune markers, we modelled the relationship between asthma and air pollution with a partial least square path model. We observed a strong positive association of IL-1RA [OR 1.37; 95% CI (1.09, 1.73)] with adult-onset asthma. Univariate models did not yield any association between air pollution and immune markers. However, mediation analyses indicated that 15% of the effect of air pollution on risk of adult-onset asthma was mediated through the immune system when considering all immune markers as a latent variable (path coefficient (β) = 0.09; 95% CI: (-0.02, 0.20)). This effect appeared to be stronger for allergic asthma (22%; β = 0.12; 95% CI: (-0.03, 0.27)) and overweight subjects (27%; β = 0.19; 95% CI: (-0.004, 0.38)). Our results provides supportive evidence for a mediating effect of the immune system in the association between air pollution and adult-onset asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-45327-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584571PMC
June 2019

Epigenome-wide association study of lung function level and its change.

Eur Respir J 2019 07 4;54(1). Epub 2019 Jul 4.

University of Groningen, University Medical Center Groningen, Dept of Epidemiology, Groningen, The Netherlands.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and their ratio (FEV/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 ( (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV/FVC: p=3.96×10 and p=7.22×10). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV/FVC: p=2.65×10).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00457-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610463PMC
July 2019

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.

Nat Genet 2019 03 25;51(3):481-493. Epub 2019 Feb 25.

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-018-0321-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078PMC
March 2019

DNA Methylation in Inflammatory Pathways Modifies the Association between BMI and Adult-Onset Non-Atopic Asthma.

Int J Environ Res Public Health 2019 02 19;16(4). Epub 2019 Feb 19.

Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland.

A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling ( = 0.0023), MAPK signaling ( = 0.013), NF-κB signaling ( = 0.031), and PI3K/AKT signaling ( = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years ( = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph16040600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406386PMC
February 2019

Association of long-term exposure to traffic-related PM with heart rate variability and heart rate dynamics in healthy subjects.

Environ Int 2019 04 1;125:107-116. Epub 2019 Feb 1.

University of Basel, Switzerland; Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Epidemiological evidence on the influence of long-term exposure to traffic-related particulate matter (TPM) on heart rate variability (HRV) is weak.

Objective: To evaluate the association of long-term exposure (10 years) with TPM on the regulation of the autonomic cardiovascular system and heart rate dynamics (HRD) in an aging general population, as well as potential modifying effects by the a priori selected factors sex, smoking status, obesity, and gene variation in selected glutathione S-transferases (GSTs).

Methods: We analyzed data from 1593 SAPALDIA cohort participants aged ≥ 50 years. For each participant, various HRV and HRD parameters were derived from 24-hour electrocardiogram recordings. Each parameter obtained was then used as the outcome variable in multivariable mixed linear regression models in order to evaluate the association with TPM. Potential modifying effects were assessed using interaction terms.

Results: No association between long-term exposure to TPM and HRV/HRD was observed in the entire study population. However, HRD changes were found in subjects without cardiovascular morbidity and both HRD and HRV changes in non-obese subjects without cardiovascular morbidity. Subjects without cardiovascular morbidity with homozygous GSTM1 gene deletion appeared to be more susceptible to the effects of TPM.

Conclusion: This study suggests that long-term exposure to TPM triggers adverse changes in the regulation of the cardiovascular system. These adverse effects were more visible in the subjects without cardiovascular disease, in whom the overall relationship between TPM and HRV/HRD could not be masked by underlying morbidities and the potential counteracting effects of related drug treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2019.01.031DOI Listing
April 2019

Restrictive spirometry pattern is associated with low physical activity levels. A population based international study.

Respir Med 2019 01 15;146:116-123. Epub 2018 Dec 15.

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry.

Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV/FVC ≥ Lower Limit of Normal and a FVC<80% predicted in two population-based studies (ECRHS-III and SAPALDIA3). Physical activity was measured using the International Physical Activity Questionnaire. The odds of having low physical activity (<1st study-specific tertile) was evaluated using adjusted logistic regression models.

Results: Subjects with a restrictive spirometry pattern (n = 280/4721 in ECRHS, n = 143/3570 in SAPALDIA) reported lower levels of physical activity than those with normal spirometry (median of 1770 vs 2253 MET·min/week in ECRHS, and 3519 vs 3945 MET·min/week in SAPALDIA). Subjects with a restrictive spirometry pattern were more likely to report low physical activity (meta-analysis odds ratio: 1.41 [95%CI 1.07-1.86]) than those with a normal spirometry. Obesity, respiratory symptoms, co-morbidities and previous physical activity levels did not fully explain this finding.

Conclusion: Adults with a restrictive spirometry pattern were more likely to report low levels of physical activity than those with normal spirometry. These results highlight the need to identify and act on this understudied but prevalent condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2018.11.017DOI Listing
January 2019

Association between helminth infections and diabetes mellitus in adults from the Lao People's Democratic Republic: a cross-sectional study.

Infect Dis Poverty 2018 Nov 6;7(1):105. Epub 2018 Nov 6.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, PO Box, 4002, 4051, Basel, Switzerland.

Background: As a result of epidemiological transition, the health systems of low- and middle-income countries are increasingly faced with a dual disease burden of infectious diseases and emerging non-communicable diseases. Little is known about the mutual influence of these two disease groups. The aim of this study was to investigate the co-occurrence of helminth infections and diabetes mellitus in adults in Lao People's Democratic Republic (Lao PDR).

Methods: We conducted a cross-sectional study among 1600 randomly selected adults aged 35 and older from four different socio-economical and ecological provinces. Information on socio-demographics, risk factors and health conditions was obtained from personal interviews. Clinical assessments including anthropometry (height, weight, waist and hip circumference) and blood pressure measurements were also conducted. Diabetes was classified based on self-reported diagnoses and a point-of-care glycated haemoglobin (HbA1c) test from finger prick blood samples. Stool samples for helminth diagnosis were examined with formalin-ether concentration technique for intestinal parasitic infections. The independent associations of helminth infections with diabetic status and HbA1c were assessed using multiple regression analyses.

Results: The prevalence of pre-diabetes and diabetes was 37.3% and 22.8%, respectively. Fifty-six percent of diabetic cases were undiagnosed and 85% of diagnosed diabetic cases had poor glycemic control. Participants from rural areas and from southern parts of the country had higher infection rates, with Opisthorchis viverrini, being the most common helminth infection (30.5%). We found a positive association between Taenia spp. infections and HbA1c (β = 0.117; 95% CI: 0.042-0.200) and diabetes mellitus risk (OR = 2.98; 95% CI: 1.10-8.05). No other helminth species was associated with glycated hemoglobin.

Conclusions: Hyperglycaemia and diabetic rates in Lao PDR are alarmingly high, but consistent with other high rates in the region. Given the high rates of under-diagnosis and poorly-controlled glycaemia in diabetes mellitus patients, routine diabetes screening and treatment is essential for the local healthcare system. Large longitudinal cohorts integrating biomarkers are warranted in the search of causal diabetes mellitus risk factors in the region. Common intestinal helminth infections, including O. viverrini, are unlikely to explain the high diabetes mellitus rates observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40249-018-0488-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219195PMC
November 2018

Meta-analysis of exome array data identifies six novel genetic loci for lung function.

Wellcome Open Res 2018 12;3. Epub 2018 Jan 12.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC 27514, USA.

Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV ), forced vital capacity (FVC) and the ratio of FEV to FVC (FEV /FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. We identified significant (P<2·8x10 ) associations with six SNPs: a nonsynonymous variant in , which is predicted to be damaging, three intronic SNPs ( and ) and two intergenic SNPs near to and Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including and . Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/wellcomeopenres.12583.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081985PMC
January 2018

SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts.

Respir Res 2018 Aug 22;19(1):156. Epub 2018 Aug 22.

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.

Background: The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort.

Methods: DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models.

Results: Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing.

Conclusions: The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-018-0850-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103990PMC
August 2018
-->