Genome wide association study of Preserved Ratio Impaired Spirometry (PRISm)

Background: Preserved Ratio Impaired Spirometry (PRISm) is defined as FEV1 &lt;80% predicted, FEV1/FVC ≥0.70. PRISm is associated with respiratory symptoms and co-morbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated co-morbidities.Methods: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected SNPs reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait Linkage Disequilibrium score regression to estimate genome-wide genetic correlation between PRISM and pulmonary and extra-pulmonary traits. Phenome-wide association studies of top SNPs was performed. Results: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg = 0.62, p-value &lt;0.001) was observed, and genetic correlation with type II diabetes (rg = 0.12, p-value 0.007). PheWAS showed that 18 of 22 signals were associated with diabetic traits and 7 with blood pressure traits.Discussion: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals; rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B) have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extra-pulmonary co-morbidity.<br/

Late Bronze Age pottery production: evidence from a 12th–11th century cal BC settlement at Tinney's Lane, Sherborne, Dorset

Excavations at Tinney's Lane, Sherborne in 2002 uncovered extensive evidence for Late Bronze Age settlement and pottery production, dating from a short time period probably within the 12th or 11th century cal bc . Well-preserved deposits of burnt stone, broken vessels, and burnt sherds, together with resulting debris redeposited in associated pits, were accompanied by a series of post-hole structures interpreted as round-houses and four-post settings. Environmental evidence in the form of charcoal, charred plant remains, and molluscs has provided important information concerning sources of fuel and water for pottery production as well as allowing a reconstruction of the local vegetation. Finds of fired clay, metal, stone, shale, flint, and bone include items from distant sources, informing topics such as site status and exchange, and include many categories of tools and equipment that would have been used within the pottery-making processes. Analysis of the spatial distribution of these finds amongst the structures and surviving layers of burning has allowed the definition of a series of industrial activity areas, each comprising one or more round-houses, a four-post structure, bonfire bases or pits used for firing, and other pits with specific related functions. Altogether the site has provided some of the best evidence for pottery production within prehistoric Britain