Adiposity and asthma in adults: a bidirectional Mendelian randomization analysis of the HUNT Study

This article has been accepted for publication in Thorax, 2019 following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/thoraxjnl-2019-213678. © Authors (or their employer(s))Background - We aimed to investigate the potential causal associations of adiposity with asthma overall, asthma by atopic status or by levels of symptom control in a large adult population and stratified by sex. We also investigated the potential for reverse causation between asthma and risk of adiposity. Methods - We performed a bidirectional one-sample Mendelian randomisation (MR) study using the Norwegian Nord-Trøndelag Health Study population including 56 105 adults. 73 and 47 genetic variants were included as instrumental variables for body mass index (BMI) and waist-to-hip ratio (WHR), respectively. Asthma was defined as ever asthma, doctor-diagnosed asthma and doctor-diagnosed active asthma, and was further classified by atopic status or levels of symptom control. Causal OR was calculated with the Wald method. Results - The ORs per 1 SD (4.1 kg/m2) increase in genetically determined BMI were ranged from 1.36 to 1.49 for the three asthma definitions and similar for women and men. The corresponding ORs for non-atopic asthma (range 1.42–1.72) appeared stronger than those for the atopic asthma (range 1.18–1.26), but they were similar for controlled versus partly controlled doctor-diagnosed active asthma (1.43 vs 1.44). There was no clear association between genetically predicted WHR and asthma risk or between genetically predicted asthma and the adiposity markers. Conclusions - Our MR study provided evidence of a causal association of BMI with asthma in adults, particularly with non-atopic asthma. There was no clear evidence of a causal link between WHR and asthma or of reverse causation

Soil heterogeneity in the horizontal distribution of microplastics influences productivity and species composition of plant communities

Contamination of soils by microplastics can have profound ecological impacts on terrestrial ecosystems and has received increasing attention. However, few studies have considered the impacts of soil microplastics on plant communities and none has tested the impacts of spatial heterogeneity in the horizontal distribution of microplastics in the soil on plant communities. We grew experimental plant communities in soils with either a homogeneous or a heterogeneous distribution of each of six common microplastics, i.e., polystyrene foam (EPS), polyethylene fiber (PET), polyethylene bead (HDPE), polypropylene fiber (PP), polylactic bead (PLA) and polyamide bead (PA6). The heterogeneous treatment consisted of two soil patches without microplastics and two with a higher (0.2%) concentration of microplastics, and the homogeneous treatment consisted of four patches all with a lower (0.1%) concentration of microplastics. Thus, the total amounts of microplastics in the soils were exactly the same in the two treatments. Total and root biomass of the plant communities were significantly higher in the homogeneous than in the heterogeneous treatment when the microplastic was PET and PP, smaller when it was PLA, but not different when it was EPS, HDPE or PA6. In the heterogeneous treatment, total and root biomass were significantly smaller in the patches with than without microplastics when the microplastic was EPS, but greater when the microplastic was PET or PP. Additionally, in the heterogeneous treatment, root biomass was significantly smaller in the patches with than without microplastics when the microplastic was HDPE, and shoot biomass was also significantly smaller when the microplastic was EPS or PET. The heterogeneous distribution of EPS in the soil significantly decreased community evenness, but the heterogeneous distribution of PET increased it. We conclude that soil heterogeneity in the horizontal distribution of microplastics can influence productivity and species composition of plant communities, but such an effect varies depending on microplastic chemical composition (types) and morphology (shapes)

Comparison of pre- and post-bronchodilator lung function as predictors of mortality:The HUNT Study

Background and objective Post‐bronchodilator (BD) lung function is recommended for the diagnosis of chronic obstructive pulmonary disease (COPD). However, often only pre‐BD lung function is used in clinical practice or epidemiological studies. We aimed to compare the discrimination ability of pre‐BD and post‐BD lung function to predict all‐cause mortality. Methods Participants aged ≥40 years with airflow limitation (n = 2538) and COPD (n = 1262) in the second survey of the Nord‐Trøndelag Health Study (HUNT2, 1995–1997) were followed up until 31 December 2015. Survival analysis and time‐dependent area under the receiver operating characteristic curves (AUC) were used to compare the discrimination ability of pre‐BD and post‐BD lung function (percent‐predicted forced expiratory volume in the first second (FEV1) (ppFEV1), FEV1 z‐score, FEV1 quotient (FEV1Q), modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) categories or GOLD grades). Results Among 2538 participants, 1387 died. The AUC for pre‐BD and post‐BD ppFEV1 to predict mortality were 60.8 and 61.8 (P = 0.005), respectively, at 20 years' follow‐up. The corresponding AUC for FEV1 z‐score were 58.5 and 60.4 (P < 0.001), for FEV1Q were 68.7 and 70.1 (P = 0.002) and for modified GOLD categories were 62.3 and 64.5 (P < 0.001). Among participants with COPD, the AUC for pre‐BD and post‐BD ppFEV1 were 57.0 and 58.8 (P < 0.001), respectively. The corresponding AUC for FEV1 z‐score were 53.1 and 55.8 (P < 0.001), for FEV1Q were 63.6 and 65.1 (P = 0.037) and for GOLD grades were 56.0 and 57.0 (P = 0.268). Conclusion Mortality was better predicted by post‐BD than by pre‐BD lung function; however, they differed only by a small margin. The discrimination ability using GOLD grades among COPD participants was similar

Prolonged Sitting, Its Combination With Physical Inactivity and Incidence of Lung Cancer: Prospective Data From the HUNT Study

Background: Prolonged sitting as a major sedentary behavior potentially contributes to illness, but its relation with lung cancer risk is unclear. Prolonged sitting can be presented in physically active or inactive individuals. Those who are extendedly seated and also physically inactive may represent the most sedentary people. We therefore aimed to prospectively examine if total sitting time daily itself or in combination with physical activity is associated with lung cancer incidence overall and histologic types.Methods: We included 45,810 cancer-free adults who participated in the second survey of HUNT Study in Norway (1995–97), with a median follow-up of 18.3 years. Total sitting time daily and physical activity were self-reported at baseline. Lung cancer cases were ascertained from the Cancer Registry of Norway. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).Results: In total, 549 participants developed lung cancer during the follow-up. Total sitting time daily was not associated with the incidence of lung cancer overall and histologic subtypes. Compared with participants sitting &lt; 8 h daily and being physically active, those sitting ≥8 h daily (prolonged sitting) and being physically inactive had an increased incidence of lung cancer (overall: adjusted HR = 1.44, 95% CI: 1.07–1.94; small cell lung cancer: adjusted HR = 2.58, 95% CI: 1.23–5.41). Prolonged sitting only or physical inactivity only was not associated with the incidence of lung cancer.Conclusions: Our study suggested that prolonged sitting was not independently associated with lung cancer incidence. The combination of prolonged sitting and physical inactivity might increase the risk of lung cancer. However, residual confounding by smoking cannot be excluded completely even though smoking was adjusted for with detailed information

Assessing the role of genome-wide DNA methylation between smoking and risk of lung cancer using repeated measurements: the HUNT Study

Background - It is unclear if smoking-related DNA methylation represents a causal pathway between smoking and risk of lung cancer. We sought to identify novel smoking-related DNA methylation sites in blood, with repeated measurements, and to appraise the putative role of DNA methylation in the pathway between smoking and lung cancer development. Methods - We derived a nested case-control study from the Trøndelag Health Study (HUNT), including 140 incident patients who developed lung cancer during 2009–13 and 140 controls. We profiled 850 K DNA methylation sites (Illumina Infinium EPIC array) in DNA extracted from blood that was collected in HUNT2 (1995–97) and HUNT3 (2006–08) for the same individuals. Epigenome-wide association studies (EWAS) were performed for a detailed smoking phenotype and for lung cancer. Two-step Mendelian randomization (MR) analyses were performed to assess the potential causal effect of smoking on DNA methylation as well as of DNA methylation (13 sites as putative mediators) on risk of lung cancer. Results - The EWAS for smoking in HUNT2 identified associations at 76 DNA methylation sites (P –8), including 16 novel sites. Smoking was associated with DNA hypomethylation in a dose-response relationship among 83% of the 76 sites, which was confirmed by analyses using repeated measurements from blood that was collected at 11 years apart for the same individuals. Two-step MR analyses showed evidence for a causal effect of smoking on DNA methylation but no evidence for a causal link between DNA methylation and the risk of lung cancer. Conclusions - DNA methylation modifications in blood did not seem to represent a causal pathway linking smoking and the lung cancer risk

Body mass index and all cause mortality in HUNT and UK Biobank studies:linear and non-linear mendelian randomisation analyses

Objective To investigate the shape of the causal relation between body mass index (BMI) and mortality. Design Linear and non-linear mendelian randomisation analyses. Setting Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom). Participants Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank. Main outcome measures All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality. Results 12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI <18.5) and a 14% (−1% to 27%) lower risk in low normal weight participants (BMI 18.5-19.9). Non-linear mendelian randomisation indicated a J shaped relation between genetically predicted BMI and the risk of all cause mortality, with the lowest risk at a BMI of around 22-25 for the overall sample. Subgroup analyses by smoking status, however, suggested an always-increasing relation of BMI with mortality in never smokers and a J shaped relation in ever smokers. Conclusions The previously observed J shaped relation between BMI and risk of all cause mortality appears to have a causal basis, but subgroup analyses by smoking status revealed that the BMI-mortality relation is likely comprised of at least two distinct curves, rather than one J shaped relation. An increased risk of mortality for being underweight was only evident in ever smokers

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure