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

[Proceedings of the 4th International Workshop of the Lower Cretaceous Cephalopod Team (IGCP-Project 362) / Peter F. Rawson and Philip J. Hoedemaeker (editors)]: Deshayesitid ammonites from the lower Aptian (Lower Cretaceous) of North-east Greenland

Two deshayesitid ammonite assemblages are described from the Lower Cretaceous succession of the north coast of Hold with Hope, North-East Greenland, and their biostratigraphical significance is assessed. In the earlier assemblage Prodeshayesites cf. bodei and P. laeviusculus occur. The second assemblage contains Deshayesites boegvadi. The presence of P. cf. bodei suggests that the northwest European bodei Subzone of the fissicostatus Zone is represented in North-East Greenland. The occurrence of D. boegvadi, previously recorded only from Kuhn q, probably indicates the later part of the fissicostatus Zone, or the forbesi or deshayesi zones. Other occurrences of Greenland deshayesitid ammonites are discussed briefly. The new finds from Hold with Hope are important biostratigraphical records providing direct correlation between the earliest Aptian of Europe and Greenland

Lithostratigraphy of the uppermost Fossil Bluff Group (Early Cretaceous) of Alexander Island, Antarctica: history of an Albian regression

The Fossil Bluff Group of south-east Alexander Island contains strata ranging from Kimmeridgian to Albian in age and represents the infill of a fore-arc basin to the west of the Antarctic Peninsula volcanic arc. Recent field work has identified approximately 2800 m of younger rock above the 4000 m already defined, including the top of the previously described Pluto Glacier Formation. A new unit, the Rhea Corner Member is defined, near the top of the Pluto Glacier Formation. The sequence above this is named as the Neptune Glacier Formation, comprising three members, the Deimos Ridge, Triton Point and Mars Glacier members. They represent the youngest part of the Fossil Bluff Group. Both the Deimos Ridge and Mars Glacier members are fully marine, but the Triton Point Member, which is late Albian in age, contains the only record of emergent conditions in 6.8 km of strata. It is a fluvial unit and contains extensive fossil forest horizons, with standing trees up to 5 m tall preserved by widespread flood deposits. The Neptune Glacier Formation therefore records a significant regression-transgression cycle of Albian age

On the origin of fore-arc basins: new evidence of formation by rifting from the Jurassic of Alexander Island, Antarctica

The Middle Jurassic–Lower Cretaceous Fossil Bluff Group of Alexander Island, Antarctica represents the fill of a fore-arc basin unconformably overlying an accretionary complex. Like most fore-arc basins, this example had been considered to have a passive origin, as a topographic hollow between the arc and the trench-slope break. Recent discoveries of igneous rock coeval with sedimentation have altered this view. Oxfordian–Kimmeridgian basaltic and rhyolitic sills and lava flows are found in a restricted area at the north of the basin, within a single formation. Chemically, most basalts are high-Nb types, which cannot have originated in a supra-subduction zone setting. Since the age of emplacement of these rocks coincides with a gap in the record of plutonism in the Antarctic Peninsula volcanic arc, it is concluded that a late Jurassic pause in subduction led to active rifting to form the fore-arc basin