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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.
Debate persists concerning the timing and geodynamics of intercontinental collision, style of syncollisional deformation, and development of topography and fold-and-thrust belts along the >1,700-km-long Izmir-Ankara-Erzincan suture zone (IAESZ) in Turkey. Resolving this debate is a necessary precursor to evaluating the integrity of convergent margin models and kinematic, topographic, and biogeographic reconstructions of the Mediterranean domain. Geodynamic models argue either for a synchronous or diachronous collision during either the Late Cretaceous and/or Eocene, followed by Eocene slab breakoff and postcollisional magmatism. We investigate the collision chronology in western Anatolia as recorded in the sedimentary archives of the 90-km-long Saricakaya Basin perched at shallow structural levels along the IAESZ. Based on new zircon U-Pb geochronology and depositional environment and sedimentary provenance results, we demonstrate that the Saricakaya Basin is an Eocene sedimentary basin with sediment sourced from both the IAESZ and Sogut Thrust fault to the south and north, respectively, and formed primarily by flexural loading from north-south shortening along the syncollisional Sogut Thrust. Our results refine the timing of collision between the Anatolides and Pontide terranes in western Anatolia to Maastrichtian-Middle Paleocene and Early Eocene crustal shortening and basin formation. Furthermore, we demonstrate contemporaneous collision, deformation, and magmatism across the IAESZ, supporting synchronous collision models. We show that regional postcollisional magmatism can be explained by renewed underthrusting instead of slab breakoff. This new IAESZ chronology provides additional constraints for kinematic, geodynamic, and biogeographic reconstructions of the Mediterranean domain.
Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level.
A necessary adjustment of protocol for use of DPC Coat-a-Count Total Testosterone assay with saliva
(1999)
Located along the Izmir-Ankara-Erzincan Suture (IAES), the Maastrichtian - Paleogene Orhaniye Basin has yielded a highly enigmatic-yet poorly dated- Paleogene mammal fauna, the endemic character of which has suggested high faunal provincialism associated with paleogeographic isolation of the Anatolian landmass during the early Cenozoic. Despite its biogeographic significance, the tectono-stratigraphic history of the Orhaniye Basin has been poorly documented; Here, we combine sedimentary, magnetostratigraphic, and geochronological data to infer the chronology and depositional history of the Orhaniye Basin. We then assess how our new data and interpretations for the Orhaniye Basin impact (1) the timing and mechanisms of seaway closure along the IAES and (2) the biogeographic evolution of Anatolia. Our results show that the Orhaniye Basin initially developed as a forearc basin during the Maastrichtian, before shifting to a retroarc foreland basin setting sometime between the early Paleocene and 44 Ma. This chronology supports a two-step scenario for the assemblage of the central Anatolian landmass, with incipient collision during the Paleocene - Early Eocene and final seaway retreat along the IAES during the earliest Late Eocene after the last marine incursion into the foreland basin. Our dating for the Orhaniye mammal fauna (44-43 Ma) indicates the persistence of faunal endemism in northern Anatolia until at least the late Lutetian despite the advanced stage of IAES closure. The tectonic evolution of dispersal corridors linking northern Anatolia with adjacent parts of Eurasia was not directly associated with IAES closure and consecutive uplifts, but rather with the build-up of continental bridges on the margins of Anatolia, in the Alpine and Tibetan-Himalayan orogens.