Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Background Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. Findings The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74–1·88] and non-European (1·42 [1·34–1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56–9·72) in European ancestry and 4·83 (3·45–6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79–0·81] vs 0·76 [0·75–0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. Interpretation A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtyp

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Soil chemical and physical properties from a digestate (winter wheat trial) experiment at North Wyke and Henfaes Farm, UK (2017)

The data consist of soil physicochemical and biological data for three soil depths (0-15, 15-30 and 30-60 cm) from a winter wheat field experiment located at two research sites in the United Kingdom. Soil samples were collected between April 2017 and August 2017. Extractions and measurements were carried out thereafter. The sites were Rothamsted Research at North Wyke in Devon and Bangor University at Henfaes Research Station in North Wales. At each site measurements were taken from 15 plots, organised within a randomised complete block design where 5 plots did not receive fertilizers (controls), 5 plots received food-based digestate, and 5 plots received acidified food based digestate and the nitrification inhibitor 3,4-dimethylpyrazole (DMPP; ADNI). Soil samples were taken within 2 weeks of digestate application and shortly before winter wheat harvest. Microbial community composition and nitrogen genes were measured on the same soil samples and are presented in a separate dataset (https://catalogue.ceh.ac.uk/documents/391c0294-07f1-4856-b592-428bd44055ca) Soil samples were taken by members of staff from Centre of Ecology & Hydrology (Bangor), Bangor University, School of Environment, Natural Resources & Geography Sustainable Agricultural Sciences, and Rothamsted Research North Wyke. Measurements were carried out Rothamsted Research Harpenden and the Centre of Ecology & Hydrology (Wallingford). Data was collected for the Newton Fund project “UK-China Virtual Joint Centre for Improved Nitrogen Agronomy”. Funded by Biotechnology and Biological Sciences Research Council (BBSRC) and NERC - Ref BB/N013468/