Interaction with air pollution exposure for genetic loci associated with lung function

Air pollution has been found to be associated with reduced lung function; also 279 genetic signals of association with lung function have been identified that implicate multiple genes and pathways. In this study, we examined if any of these signals interact with air pollution measures NO2, PM2.5 and PM10.In 259,389 unrelated European individuals from UK Biobank, we tested for a gene-environment interaction effect on lung function with NO2, PM2.5 and PM10 for each of the 279 signals. Lung function measures (FEV1, FEV1/FVC and FVC) were adjusted for sex, age, age2, height, and smoking, income and educational status, with adjustment for 15 principal components for fine-scale population structure. A significance threshold of PWe found statistically significant evidence for an interaction with PM2.5 on FEV1/FVC for rs10841302 on chromosome 12 (minor allele frequency=45.2%, interaction P=1.55x10-5). The SNP was also nominally significant for an interaction with PM10 and NO2 (P=5.2x10-4 and 2.3x10-3, respectively). This SNP did not show an interaction with tobacco smoke in a previous analysis. A further 16 SNPs had a nominally significant (PThe gene underlying the association of rs10841302 with lung function has not been determined but the SNP lies close to the AEBP2 gene which encodes AE Binding Protein 2, a transcriptional repressor which may have a role in histone methylation. Identification and characterisation of genes whose effect is influenced by air pollution exposure will enable us to understand how the environment influences respiratory health.</p

United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol.

Introduction: COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities. Methods and analysis: This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes. Ethics and dissemination: Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/). Trial registration number: ISRCTN11811602.</p

Healthcare workers' views on mandatory SARS-CoV-2 vaccination in the UK: A cross-sectional, mixed-methods analysis from the UK-REACH study.

Several countries now have mandatory SARS-CoV-2 vaccination for healthcare workers (HCWs) or the general population. HCWs' views on this are largely unknown. Using data from the nationwide UK-REACH study we aimed to understand UK HCW's views on improving SARS-CoV-2 vaccination coverage, including mandatory vaccination.Between 21st April and 26th June 2021, we administered an online questionnaire via email to 17 891 UK HCWs recruited as part of a longitudinal cohort from across the UK who had previously responded to a baseline questionnaire (primarily recruited through email) as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question "What should society do if people do not get vaccinated against COVID-19?" using qualitative content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not, using logistic regression to calculate its demographic predictors, and its occupational, health, and attitudinal predictors adjusted for demographics.Of 5633 questionnaire respondents, 3235 answered the free text question. Median age of free text responders was 47 years (IQR 36-56) and 2705 (74.3%) were female. 18% (n = 578) favoured mandatory vaccination (201 [6%] participants for HCWs and others working with vulnerable populations; 377 [12%] for the general population), but the most frequent suggestion was education (32%, n = 1047). Older HCWs (OR 1.84; 95% CI 1.44-2.34 [≥55 years vs 16 years to <40 years]), HCWs vaccinated against influenza (OR 1.49; 95% CI 1.11-2.01 [2 vaccines vs none]), and with more positive vaccination attitudes generally (OR 1.10; 95% CI 1.06-1.15) were more likely to favour mandatory vaccination, whereas female HCWs (OR= 0.79, 95% CI 0.63-0.96, vs male HCWs) and Black HCWs (OR=0.46, 95% CI 0.25-0.85, vs white HCWs) were less likely to.Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating, and supporting HCWs who are hesitant about vaccination may be more acceptable, effective, and equitable.</p