Refine
Has Fulltext
- no (4)
Document Type
- Article (4)
Language
- English (4)
Is part of the Bibliography
- yes (4)
Keywords
- Anatolia (1)
- Eocene (1)
- collision (1)
- detrital zircons (1)
- geochronology (1)
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.
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.