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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Eilis Hannon; Emma Dempster; Georgina Mansell; Joe Burrage; +42 Authors

    We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
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    Article . 2021
    License: CC BY
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    Europe PubMed Central
    Article . 2021
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    DOAJ-Articles
    Article . 2021
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    eLife
    Article . 2021 . Peer-reviewed
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Article . 2021
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Article . 2021
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      eLife
      Article . 2021 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fereidouni, Sasan; Freimanis, Graham L.; Orynbayev, Mukhit; Ribeca, Paolo; +8 Authors

    In 2015, a mass die-off of ≈200,000 saiga antelopes in central Kazakhstan was caused by hemorrhagic septicemia attributable to the bacterium Pasteurella multocida serotype B. Previous analyses have indicated that environmental triggers associated with weather conditions, specifically air moisture and temperature in the region of the saiga antelope calving during the 10-day period running up to the event, were critical to the proliferation of latent bacteria and were comparable to conditions accompanying historically similar die-offs in the same areas. We investigated whether additional viral or bacterial pathogens could be detected in samples from affected animals using 3 different high-throughput sequencing approaches. We did not identify pathogens associated with commensal bacterial opportunisms in blood, kidney, or lung samples and thus concluded that P. multocida serotype B was the primary cause of the disease.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
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    Article . 2019
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Emerging Infectious Diseases
    Other literature type . Article . 2019 . Peer-reviewed
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2019
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Emerging Infectious Diseases
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Article . 2019
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Emerging Infectious Diseases
      Other literature type . Article . 2019 . Peer-reviewed
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Europe PubMed Central
      Other literature type . 2019
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Emerging Infectious Diseases
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    Authors: Lu, Lu; Brierley, Liam; Robertson, Gail; Zhang, Feifei; +5 Authors

    AbstractTo have epidemic potential, a pathogen must be able to spread in human populations, but of human-infective RNA viruses only a minority can do so. We investigated the evolution of human transmissibility through parallel analyses of 1755 virus genome sequences from 39 RNA virus genera. We identified 57 lineages containing human-transmissible species and estimated that at least 74% of these lineages have evolved directly from non-human viruses in other mammals or birds, a public health threat recently designated “Disease X”. Human-transmissible viruses rarely evolve from virus lineages that can infect but not transmit between humans. This result cautions against focussing surveillance and mitigation efforts narrowly on currently known human-infective virus lineages and supports calls for a better understanding of RNA virus diversity in non-human hosts.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ bioRxivarrow_drop_down
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    bioRxiv
    Preprint . 2019
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ bioRxivarrow_drop_down
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      Preprint . 2019
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    Authors: Santos, Susana; Eekhout, Iris; Voerman, Ellis; Gaillard, Romy; +76 Authors

    Figure S1. Flow chart of participating cohorts and individuals. Table S1. Cohort-specific methods of data collection for maternal anthropometrics and gestational age. Table S2. Box-Cox t model specifications for each maternal pre-pregnancy body mass index group. Table S3. Gestational weight measurements per participating cohort and maternal pre-pregnancy body mass index group. Figure S2. Sample size according to gestational age for each maternal pre-pregnancy body mass index group. Figure S3. Predicted z scores for the average weight gain according to gestational age for each maternal pre-pregnancy body mass index group. Table S4. Week-specific Box-Cox t model parameters and selected percentiles of gestational weight gain for maternal pre-pregnancy underweight. Table S5. Week-specific Box-Cox t model parameters and selected percentiles of gestational weight gain for maternal pre-pregnancy normal weight. Table S6. Week-specific Box-Cox t model parameters and selected percentiles of gestational weight gain for maternal pre-pregnancy overweight. Table S7. Week-specific Box-Cox t model parameters and selected percentiles of gestational weight gain for maternal pre-pregnancy obesity grade 1. Table S8. Week-specific Box-Cox t model parameters and selected percentiles of gestational weight gain for maternal pre-pregnancy obesity grade 2. Table S9. Week-specific Box-Cox t model parameters and selected percentiles of gestational weight gain for maternal pre-pregnancy obesity grade 3. Table S10. Local institutional ethical review boards per cohort. (DOCX 631 kb)

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    Other literature type . 2018
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    Other literature type . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ figsharearrow_drop_down
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      Other literature type . 2018
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Other literature type . 2018
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Katherine M. Livingstone; Carlos Celis-Morales; George D. Papandonatos; Bahar Erar; +28 Authors

    Objective To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. Design Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. Data sources Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. Eligibility criteria for study selection Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. Results We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. Conclusions We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. Systematic review registration PROSPERO CRD42015015969.

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    Article . 2017 . Peer-reviewed
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      Article . 2017 . Peer-reviewed
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    Authors: Jorrit L. Opstelten; Rob Beelen; Max Leenders; Gerard Hoek; +16 Authors

    Background Industrialization has been linked to the etiology of inflammatory bowel disease (IBD). Aim We investigated the association between air pollution exposure and IBD. Methods The European Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn’s disease (CD) (n = 38) and ulcerative colitis (UC) (n = 104) and controls (n = 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 μm (PM10), <2.5 μm (PM2.5), and between 2.5 and 10 μm (PMcoarse), soot (PM2.5 absorbance), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs). Results Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM2.5 and PM10, with ORs of 0.24 (95 % CI 0.07–0.81) per 5 μg/m3 and 0.25 (95 % CI 0.08–0.78) per 10 μg/m3, respectively. There was an inverse but nonsignificant association for PMcoarse. A higher nearby traffic load was positively associated with IBD [OR 1.60 (95 % CI 1.04–2.46) per 4,000,000 motor vehicles × m per day]. Other air pollutants were positively but not significantly associated with IBD. Conclusion Exposure to air pollution was not found to be consistently associated with IBD. Electronic supplementary material The online version of this article (doi:10.1007/s10620-016-4249-4) contains supplementary material, which is available to authorized users.

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    Europe PubMed Central
    Article . 2016
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    Radboud Repository
    Article . 2016
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    Digestive Diseases and Sciences
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    Oxford University Research Archive
    Other literature type . 2016
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    Digestive Diseases and Sciences
    Article . 2016 . Peer-reviewed
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      Digestive Diseases and Sciences
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      Other literature type . 2016
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      Digestive Diseases and Sciences
      Article . 2016 . Peer-reviewed
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    Authors: J. H. Forth; Leonie Forth; Samantha Lycett; Lesley Bell-Sakyi; +8 Authors

    BACKGROUND: African swine fever virus (ASFV) is a most devastating pathogen affecting swine. In 2007, ASFV was introduced into Eastern Europe where it continuously circulates and recently reached Western Europe and Asia, leading to a socio-economic crisis of global proportion. In Africa, where ASFV was first described in 1921, it is transmitted between warthogs and soft ticks of the genus Ornithodoros in a so-called sylvatic cycle. However, analyses into this virus’ evolution are aggravated by the absence of any closely related viruses. Even ancient endogenous viral elements, viral sequences integrated into a host’s genome many thousand years ago that have proven extremely valuable to analyse virus evolution, remain to be identified. Therefore, the evolution of ASFV, the only known DNA virus transmitted by arthropods, remains a mystery. - RESULTS: For the identification of ASFV-like sequences, we sequenced DNA from different recent Ornithodoros tick species, e.g. O. moubata and O. porcinus, O. moubata tick cells and also 100-year-old O. moubata and O. porcinus ticks using high-throughput sequencing. We used BLAST analyses for the identification of ASFV-like sequences and further analysed the data through phylogenetic reconstruction and molecular clock analyses. In addition, we performed tick infection experiments as well as additional small RNA sequencing of O. moubata and O. porcinus soft ticks. - CONCLUSION: Here, we show that soft ticks of the Ornithodoros moubata group, the natural arthropod vector of ASFV, harbour African swine fever virus-like integrated (ASFLI) elements corresponding to up to 10% (over 20 kb) of the ASFV genome. Through orthologous dating and molecular clock analyses, we provide data suggesting that integration could have occurred over 1.47 million years ago. Furthermore, we provide data showing ASFLI-element specific siRNA and piRNA in ticks and tick cells allowing for speculations on a possible role of ASFLI-elements in RNA interference-based protection against ASFV in ticks. We suggest that these elements, shaped through many years of co-evolution, could be part of an evolutionary virus-vector ‘arms race’, a finding that has not only high impact on our understanding of the co-evolution of viruses with their hosts but also provides a glimpse into the evolution of ASFV. Background Results - Evidence of ASFLI-elements in the O. moubata tick cell genome - Phylogenetic analysis shows ASFLI-elements are close relatives of ASFV sequences - ASFLI-elements are present in recently sampled O.moubata, O. porcinus and approx. 100-year-old O.moubata and O. porcinus field-collected ticks from Africa - Phylogenetic reconstruction using full-length mitochondrial genomes of soft ticks reveals a possible integration of an ASFLI-element might have occurred over 1.46–1.47 million years ago (mya) - Molecular clock analyses using ASFLI-elements from different Ornithodoros species provide an estimate for a time to the most recent common ancestor consistent with orthologous dating - Ornithodoros tick species and tick cell lines show differences in the infectability with various ASFV genotype isolates - RNA sequencing demonstrates ASFLI-element-specific mRNA—small-interfering and piwi-interacting RNAs in tick cells - The reconstructed ASFLI-A104R protein is highly similar to its ASFV homologue but is not expressed in tick cell lines Discussion Conclusion Methods - Virus strains - Tick rearing, tick infection and tick cell cultures - Nucleic acid extraction - Oligonucleotide design - PCR - qPCR - RT-qPCR - Sanger sequencing - Next-generation sequencing - Amplicon sequencing for assembly validation - Data analysis - Phylogenetic analysis - Clock rate estimates and Bayesian time-scaled trees - Protein expression and purification in E. coli and rabbit immunisation - Transfection - SDS-PAGE and immunoblotting - Statistical analysis

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    Authors: Forth, Jan H.; Forth, Leonie F.; Lycett, Samantha; Bell-Sakyi, Lesley; +8 Authors

    Additional file 13: Figure S4. siRNA/piRNA mapping against ASFV-Kenya1950 (GT X), Warthog (G IV) and two ASFLI-elements. siRNA (22 nt) and piRNA (28-29 nt) fractions from Ornithodoros porcinus were individually mapped against available ASFV whole-genome sequences (the ones showing the most mapped reads, ASFV-Kenya1950 (GT X), ASFV Wathog (GT IV) are shown) and two exemplary O. porcinus ASFLI-element containing contigs (NODE955 and NODE1089) using Bowtie 1 (1.1.2) in Geneious. Marked (arrows) are the most abundant small RNA molecules relating to the ASFV genes and ASFLI-elements.

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    Authors: Gehring, U; Gruzieva, O; Agius, RM; Beelen, R; +20 Authors

    Background: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. Objectives: We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol. Methods: As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6–8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5–10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis. Results: Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from –0.86% (95% CI: –1.48, –0.24%) for a 20-μg/m3 increase in NOx to –1.77% (95% CI: –3.34, –0.18%) for a 5-μg/m3 increase in PM2.5. Conclusions: Exposure to air pollution may result in reduced lung function in schoolchildren. Citation: Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klümper C, Korek M, Mölter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B. 2013. Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364; http://dx.doi.org/10.1289/ehp.1306770

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    Authors: Olena Gruzieva; Cheng-Jian Xu; Paul Yousefi; Caroline L Relton; +50 Authors

    Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter <10 (PM10) or <2.5 mu m (PM2.5) and DNA methylation in newborns and children. Methods: We meta-analyzed associations between exposure to PM10 (n=1,949) and PM2.5 (n=1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. Results: Six CpGs were significantly associated [false discovery rate (FDR) <0.05] with prenatal PM10 and 14 with PM2.5 exposure. Two of the PM10-related CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant (p<0.05) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent PM10 exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM10 and or PM2.5 exposure, of which two PM10-related DMRs, including H19 and MARCH11, replicated in newborns. Conclusions: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. ALSPAC: The UK Medical Research Council and the Wellcome Trust (Grant ref. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and P.Y. will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristoLac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by a joint grant from the UK Economic & Social and Biotechnology & Biological Sciences Research Councils (Grant ref. ES/N000498/1). ALSPAC was funded by the BBSRC (BBI025751/1 and BB/I025263/1). Air pollution exposure assessment was funded by Public Health England as part of the MRC-PHE Centre for Environment and Health, funded also by the UK Medical Research Council (Grant ref. MR/L01341X/1). This paper does not necessarily reflect the views of Public Health England or the Department of Health. BAMSE was supported by The Swedish Research Council, The Swedish Heart-Lung Foundation, Freemason Child House Foundation in Stockholm, MeDALL (Mechanisms of the Development of ALLergy) a collaborative project conducted within the European Union (grant agreement No. 261357), Centre for Allergy Research, Stockholm County Council (ALE), Swedish Foundation for Strategic Research (SSF) (RBc08-0027), the Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet, The Swedish Research Council Foams, and the Swedish Environment Protection Agency. E.M. is supported by a grant from the European Research Council under the European Union (EU) Horizon 2020 (H2020) research and innovation programme (grant agreement number 757919, TRIBAL). O.G. is supported by Forte (Swedish Research Council for Health, Working Life and Welfare) and The Swedish Society for Medical Research. CHS: This work was supported by NIEHS grants K01ES017801, R01ES022216, and P30ES007048. EARLI: This work was supported by NIH grants R01ES016443, R01ES023780, and R01ES017646 as well as by Autism Speaks (AS 5938). ENVIRONAGE: The ENVIRONAGE birth cohort is funded by the European Research Counsil (ERC-2012-StG.310898) and by funds of the Flemisch Scientific Research Council (FWO, N1516112/G.0.873.11N.10). The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (Grant agreement no. 308610). ZH and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA-Inserm, France) and Association pour la Recherche sur le Cancer (ARC, France). Generation R Study: The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center (MC), Rotterdam, the Erasmus University Rotterdam, Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The EWAS data was funded by a grant to VWJ from Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project no. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC. V.W.J. also received a grant from Netherlands Organization for Health Research and Development (VIDI 016.136.361) and a Consolidator Grant from the European Research Council (ERC-2014-CoG-648916). J.F.F. has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 633595 (DynaHEALTH). This project received funding from the European Union's Horizon 2020 Research and Innovation Programme (733206, LIFECYCLE). HELIX: The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 - the HELIX project. R.G. received the grant of the Lithuanian Agency for Science Innovation and Technology (No. 45 31V-66). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). INMA: This study was funded by grants from Institut() de Salud Carlos III (Red INMA G03/176), Generalitat de Catalunya-CIRIT 1999SGR 00241, and EU Commission (261357; 211250; 268479). Piccolipiu: The study was approved and initially funded by the Italian National Centre for Disease Prevention and Control (CCM grant 2010) and by the Italian Ministry of Health (art 12 and 12bis Dl.gs.vo 502/92). The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (Grant agreement no: 308610). Z.H. and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA-INSERM, France) and Association pour la Recherche sur le Cancer (ARC, France). Rhea: The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (grant agreement no. 308610). ZH and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA INSERM, France) and Association pour la Recherche sur le Cancer (ARC, France). PRISM: R.J.W. received funding for the PRISM cohort under HL095606 and R01 HL1143396. A.C.J. is supported by R00 ES023450. Project Viva: This Project Viva study was supported by grants from the NIH (NIH R01 HL 111108, R01 NR013945, R01 HD 034568, K24 HD069408, K23 ES022242, P01ES009825, R01AI102960, P30 ES000002) and the U.S. Environmental Protection Agency (EPA) (R832416, RD834798). This publication's contents are solely the responsibility of the grantee and do not necessarily represent the official views of the U.S. Government, the U.S. Department of Health and Human Services or the NIH, or the EPA. Further, the EPA does not endorse the purchase of any commercial products or services mentioned in the publication. MeDALL: The methylation study of MeDALL cohorts was funded by MEDALL, a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework Programme (grant agreement no. 261357). The Biobank-Based Integrative Omics Studies (BIOS) Consortium is funded by BBMRI-NL, a research 'infrastructure financed by the Dutch government (NWO 184.021.007). BAMSE: We would like to thank all the families for their participation in the BAMSE study. In addition, we would like to thank E. Haliner, S. Nilsson, and A. Lauber at the BAMSE secretary for invaluable support, as well as Mutation Analysis Facility (MAF) at Karolinska Institutet for genome-wide methylation analysis, and I. Delin for excellent technical assistance. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b201.4110.

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