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Trauth, Martin H. ; Bergner, Andreas G. N. ; Foerster, Verena ; Junginger, Annett ; Maslin, Mark A. ; Schäbitz, Frank
Episodes of environmental stability and instability may be equally important for African hominin speciation, dispersal, and cultural innovation. Three examples of a change from stable to unstable environmental conditions are presented on three different time scales: (1) the Mid Holocene (MH) wet dry transition in the Chew Bahir basin (Southern Ethiopian Rift; between 11 ka and 4 ka), (2) the MIS 5-4 transition in the Naivasha basin (Central Kenya Rift; between 160 ka and 50 ka), and (3) the Early Mid Pleistocene Transition (EMPT) in the Olorgesailie basin (Southern Kenya Rift; between 1.25 Ma and 0.4 Ma). A probabilistic age modeling technique is used to determine the timing of these transitions, taking into account possible abrupt changes in the sedimentation rate including episodes of no deposition (hiatuses). Interestingly, the stable-unstable conditions identified in the three records are always associated with an orbitally-induced decrease of insolation: the descending portion of the 800 kyr cycle during the EMPT, declining eccentricity after the 115 ka maximum at the MIS 5-4 transition, and after similar to 10 ka. This observation contributes to an evidence-based discussion of the possible mechanisms causing the switching between environmental stability and instability in Eastern Africa at three different orbital time scales (10,000 to 1,000,000 years) during the Cenozoic. This in turn may lead to great insights into the environmental changes occurring at the same time as hominin speciation, brain expansion, dispersal out of Africa, and cultural innovations and may provide key evidence to build new hypotheses regarding the causes of early human evolution. (C) 2015 Elsevier Ltd. All rights reserved.
Arnison, Paul G. ; Bibb, Mervyn J. ; Bierbaum, Gabriele ; Bowers, Albert A. ; Bugni, Tim S. ; Bulaj, Grzegorz ; Camarero, Julio A. ; Campopiano, Dominic J. ; Challis, Gregory L. ; Clardy, Jon ; Cotter, Paul D. ; Craik, David J. ; Dawson, Michael ; Dittmann-Thünemann, Elke ; Donadio, Stefano ; Dorrestein, Pieter C. ; Entian, Karl-Dieter ; Fischbach, Michael A. ; Garavelli, John S. ; Goeransson, Ulf ; Gruber, Christian W. ; Haft, Daniel H. ; Hemscheidt, Thomas K. ; Hertweck, Christian ; Hill, Colin ; Horswill, Alexander R. ; Jaspars, Marcel ; Kelly, Wendy L. ; Klinman, Judith P. ; Kuipers, Oscar P. ; Link, A. James ; Liu, Wen ; Marahiel, Mohamed A. ; Mitchell, Douglas A. ; Moll, Gert N. ; Moore, Bradley S. ; Mueller, Rolf ; Nair, Satish K. ; Nes, Ingolf F. ; Norris, Gillian E. ; Olivera, Baldomero M. ; Onaka, Hiroyasu ; Patchett, Mark L. ; Piel, Jörn ; Reaney, Martin J. T. ; Rebuffat, Sylvie ; Ross, R. Paul ; Sahl, Hans-Georg ; Schmidt, Eric W. ; Selsted, Michael E. ; Severinov, Konstantin ; Shen, Ben ; Sivonen, Kaarina ; Smith, Leif ; Stein, Torsten ; Suessmuth, Roderich D. ; Tagg, John R. ; Tang, Gong-Li ; Truman, Andrew W. ; Vederas, John C. ; Walsh, Christopher T. ; Walton, Jonathan D. ; Wenzel, Silke C. ; Willey, Joanne M. ; van der Donk, Wilfred A.
This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
We modeled the two most extreme highstands of Lake Naivasha during the last 175 k.y. to estimate potential precipitation/ evaporation changes in this basin. In a first step, the bathymetry of the paleolakes at f135 and 9 k.y. BP was reconstructed from sediment cores and surface outcrops. Second, we modeled the paleohydrologic budget during the highstands using a simplified coupled energy mass-balance model. Our results show that the hydrologic and hence the climate conditions at f135 and 9 k.y. BP were similar, but significantly different from today. The main difference is a f15% higher value in precipitation compared to the present. An adaptation and migration of vegetation in the cause of climate changes would result in a f30% increase in precipitation. The most likely cause for such a wetter climate at f135 and 9 k.y. BP is a more intense intertropical convergence and increased precipitation in East Africa.
Tectonic and climatic control on evolution of rift lakes in the Central Kenya Rift, East Africa
(2009)
Bergner, Andreas G. N. ; Strecker, Manfred ; Trauth, Martin H. ; Deino, Alan L. ; Gasse, Francoise ; Blisniuk, Peter Michael ; Duehnforth, Miriam
The long-term histories of the neighboring Nakuru-Elmenteita and Naivasha lake basins in the Central Kenya Rift illustrate the relative importance of tectonic versus climatic effects on rift-lake evolution and the formation of disparate sedimentary environments. Although modem climate conditions in the Central Kenya Rift are very similar for these basins, hydrology and hydrochemistry of present-day lakes Nakuru, Elmenteita and Naivasha contrast dramatically due to tectonically controlled differences in basin geometries, catchment size, and fluvial processes. In this study, we use eighteen C-14 and Ar-40/Ar-39 dated fluvio-lacustrine sedimentary sections to unravel the spatiotemporal evolution of the lake basins in response to tectonic and climatic influences. We reconstruct paleoclimatic and ecological trends recorded in these basins based on fossil diatom assemblages and geologic field mapping. Our study shows a tendency towards increasing alkalinity and shrinkage of water bodies in both lake basins during the last million years. Ongoing volcano-tectonic segmentation of the lake basins, as well as reorganization of upstream drainage networks have led to contrasting hydrologic regimes with adjacent alkaline and freshwater conditions. During extreme wet periods in the past, such as during the early Holocene climate optimum, lake levels were high and all basins evolved toward freshwater systems. During drier periods some of these lakes revert back to alkaline conditions, while others maintain freshwater characteristics. Our results have important implications for the use and interpretation of lake sediment as climate archives in tectonically active regions and emphasize the need to deconvolve lacustrine records with respect to tectonics versus climatic forcing mechanisms.
Trauth, Martin H. ; Maslin, Mark A. ; Deino, Alan L. ; Strecker, Manfred ; Bergner, Andreas G. N. ; Dühnforth, Miriam
The late Cenozoic climate of East Africa is punctuated by episodes of short, alternating periods of extreme wetness and aridity, superimposed on a regime of subdued moisture availability exhibiting a long-term drying trend. These periods of extreme climate variability appear to correlate with maxima in the 400-thousand-year (kyr) component of the Earth's eccentricity cycle. Prior to 2.7 Ma the wet phases appear every 400 kyrs, whereas after 2.7 Ma, the wet phases appear every 800 kyrs, with periods of precessional-forced extreme climate variability at 2.7-2.5 Ma, 1.9-1.7 Ma, and 1.1-0.9 Ma before present. The last three major lake phases occur at the times of major global climatic transitions, such as the onset of Northern Hemisphere Glaciation (2.7-2.5 Ma), intensification of the Walker Circulation (1.9-1.7 Ma), and the Mid-Pleistocene Revolution (1.0-0.7 Ma). High-latitude forcing is required to compress the Intertropical Convergence Zone so that East Africa becomes locally sensitive to precessional forcing, resulting in rapid shifts from wet to dry conditions. These periods of extreme climate variability may have provided a catalyst for evolutionary change and driven key speciation and dispersal events amongst mammals and hominins in East Africa. (C) 2007 Elsevier Ltd. All rights reserved.
Variations in the temporal and spatial distribution of solar radiation caused by orbital changes provide a partial explanation for the observed long-term fluctuations in African lake levels. The understanding of such relationships is essential for designing climate-prediction models for the tropics. Our assessment of the nature and timing of East African climate change is based on lake-level fluctuations of Lake Naivasha in the Central Kenya Rift (0°55'S 36°20'E), inferred from sediment characteristics, diatoms, authigenic mineral assemblages and 17 single-crystal 40Ar/39Ar age determinations. Assuming that these fluctuations reflect climate changes, the Lake Naivasha record demonstrates that periods of increased humidity in East Africa mainly followed maximum equatorial solar radiation in March or September. Interestingly, the most dramatic change in the Naivasha Basin occurred as early as 146 kyr BP and the highest lake level was recorded at about 139 to 133 kyr BP. This is consistent with other well-dated low-latitude climate records, but does not correspond to peaks in Northern Hemisphere summer insolation as the trigger for the ice- age cycles. The Naivasha record therefore provides evidence for low-latitude forcing of the ice-age climate cycles.
de Jong, S. ; Kukreja, R. ; Trabant, C. ; Pontius, N. ; Chang, C. F. ; Kachel, T. ; Beye, Martin ; Sorgenfrei, Nomi ; Back, C. H. ; Braeuer, B. ; Schlotter, W. F. ; Turner, J. J. ; Krupin, O. ; Doehler, M. ; Zhu, D. ; Hossain, M. A. ; Scherz, A. O. ; Fausti, D. ; Novelli, F. ; Esposito, M. ; Lee, W. S. ; Chuang, Y. D. ; Lu, D. H. ; Moore, R. G. ; Yi, M. ; Trigo, M. ; Kirchmann, P. ; Pathey, L. ; Golden, M. S. ; Buchholz, Marcel ; Metcalf, P. ; Parmigiani, F. ; Wurth, W. ; Föhlisch, Alexander ; Schuessler-Langeheine, Christian ; Duerr, H. A.
As the oldest known magnetic material, magnetite (Fe3O4) has fascinated mankind for millennia. As the first oxide in which a relationship between electrical conductivity and fluctuating/localized electronic order was shown(1), magnetite represents a model system for understanding correlated oxides in general. Nevertheless, the exact mechanism of the insulator-metal, or Verwey, transition has long remained inaccessible(2-8). Recently, three- Fe- site lattice distortions called trimeronswere identified as the characteristic building blocks of the low-temperature insulating electronically ordered phase(9). Here we investigate the Verwey transition with pump- probe X- ray diffraction and optical reflectivity techniques, and show how trimerons become mobile across the insulator-metal transition. We find this to be a two- step process. After an initial 300 fs destruction of individual trimerons, phase separation occurs on a 1.5 +/- 0.2 ps timescale to yield residual insulating and metallic regions. This work establishes the speed limit for switching in future oxide electronics(10).
Mantzouki, Evanthia ; Campbell, James ; van Loon, Emiel ; Visser, Petra ; Konstantinou, Iosif ; Antoniou, Maria ; Giuliani, Gregory ; Machado-Vieira, Danielle ; de Oliveira, Alinne Gurjao ; Maronic, Dubravka Spoljaric ; Stevic, Filip ; Pfeiffer, Tanja Zuna ; Vucelic, Itana Bokan ; Zutinic, Petar ; Udovic, Marija Gligora ; Plenkovic-Moraj, Andelka ; Tsiarta, Nikoletta ; Blaha, Ludek ; Geris, Rodan ; Frankova, Marketa ; Christoffersen, Kirsten Seestern ; Warming, Trine Perlt ; Feldmann, Tonu ; Laas, Alo ; Panksep, Kristel ; Tuvikene, Lea ; Kangro, Kersti ; Haggqvist, Kerstin ; Salmi, Pauliina ; Arvola, Lauri ; Fastner, Jutta ; Straile, Dietmar ; Rothhaupt, Karl-Otto ; Fonvielle, Jeremy Andre ; Grossart, Hans-Peter ; Avagianos, Christos ; Kaloudis, Triantafyllos ; Triantis, Theodoros ; Zervou, Sevasti-Kiriaki ; Hiskia, Anastasia ; Gkelis, Spyros ; Panou, Manthos ; McCarthy, Valerie ; Perello, Victor C. ; Obertegger, Ulrike ; Boscaini, Adriano ; Flaim, Giovanna ; Salmaso, Nico ; Cerasino, Leonardo ; Koreiviene, Judita ; Karosiene, Jurate ; Kasperoviciene, Jurate ; Savadova, Ksenija ; Vitonyte, Irma ; Haande, Sigrid ; Skjelbred, Birger ; Grabowska, Magdalena ; Karpowicz, Maciej ; Chmura, Damian ; Nawrocka, Lidia ; Kobos, Justyna ; Mazur-Marzec, Hanna ; Alcaraz-Parraga, Pablo ; Wilk-Wozniak, Elzbieta ; Krzton, Wojciech ; Walusiak, Edward ; Gagala, Ilona ; Mankiewicz-Boczek, Joana ; Toporowska, Magdalena ; Pawlik-Skowronska, Barbara ; Niedzwiecki, Michal ; Peczula, Wojciech ; Napiorkowska-Krzebietke, Agnieszka ; Dunalska, Julita ; Sienska, Justyna ; Szymanski, Daniel ; Kruk, Marek ; Budzynska, Agnieszka ; Goldyn, Ryszard ; Kozak, Anna ; Rosinska, Joanna ; Szelag-Wasielewska, Elzbieta ; Domek, Piotr ; Jakubowska-Krepska, Natalia ; Kwasizur, Kinga ; Messyasz, Beata ; Pelechata, Aleksandra ; Pelechaty, Mariusz ; Kokocinski, Mikolaj ; Madrecka, Beata ; Kostrzewska-Szlakowska, Iwona ; Frak, Magdalena ; Bankowska-Sobczak, Agnieszka ; Wasilewicz, Michal ; Ochocka, Agnieszka ; Pasztaleniec, Agnieszka ; Jasser, Iwona ; Antao-Geraldes, Ana M. ; Leira, Manel ; Hernandez, Armand ; Vasconcelos, Vitor ; Morais, Joao ; Vale, Micaela ; Raposeiro, Pedro M. ; Goncalves, Vitor ; Aleksovski, Boris ; Krstic, Svetislav ; Nemova, Hana ; Drastichova, Iveta ; Chomova, Lucia ; Remec-Rekar, Spela ; Elersek, Tina ; Delgado-Martin, Jordi ; Garcia, David ; Luis Cereijo, Jose ; Goma, Joan ; Carmen Trapote, Mari ; Vegas-Vilarrubia, Teresa ; Obrador, Biel ; Garcia-Murcia, Ana ; Real, Monserrat ; Romans, Elvira ; Noguero-Ribes, Jordi ; Parreno Duque, David ; Fernandez-Moran, Elisabeth ; Ubeda, Barbara ; Angel Galvez, Jose ; Marce, Rafael ; Catalan, Nuria ; Perez-Martinez, Carmen ; Ramos-Rodriguez, Eloisa ; Cillero-Castro, Carmen ; Moreno-Ostos, Enrique ; Maria Blanco, Jose ; Rodriguez, Valeriano ; Juan Montes-Perez, Jorge ; Palomino, Roberto L. ; Rodriguez-Perez, Estela ; Carballeira, Rafael ; Camacho, Antonio ; Picazo, Antonio ; Rochera, Carlos ; Santamans, Anna C. ; Ferriol, Carmen ; Romo, Susana ; Soria, Juan Miguel ; Hansson, Lars-Anders ; Urrutia-Cordero, Pablo ; Ozen, Arda ; Bravo, Andrea G. ; Buck, Moritz ; Colom-Montero, William ; Mustonen, Kristiina ; Pierson, Don ; Yang, Yang ; Verspagen, Jolanda M. H. ; Domis, Lisette N. de Senerpont ; Seelen, Laura ; Teurlincx, Sven ; Verstijnen, Yvon ; Lurling, Miquel ; Maliaka, Valentini ; Faassen, Elisabeth J. ; Latour, Delphine ; Carey, Cayelan C. ; Paerl, Hans W. ; Torokne, Andrea ; Karan, Tunay ; Demir, Nilsun ; Beklioglu, Meryem ; Filiz, Nur ; Levi, Eti E. ; Iskin, Ugur ; Bezirci, Gizem ; Tavsanoglu, Ulku Nihan ; Celik, Kemal ; Ozhan, Koray ; Karakaya, Nusret ; Kocer, Mehmet Ali Turan ; Yilmaz, Mete ; Maraslioglu, Faruk ; Fakioglu, Ozden ; Soylu, Elif Neyran ; Yagci, Meral Apaydin ; Cinar, Sakir ; Capkin, Kadir ; Yagci, Abdulkadir ; Cesur, Mehmet ; Bilgin, Fuat ; Bulut, Cafer ; Uysal, Rahmi ; Koker, Latife ; Akcaalan, Reyhan ; Albay, Meric ; Alp, Mehmet Tahir ; Ozkan, Korhan ; Sevindik, Tugba Ongun ; Tunca, Hatice ; Onem, Burcin ; Richardson, Jessica ; Edwards, Christine ; Bergkemper, Victoria ; Beirne, Eilish ; Cromie, Hannah ; Ibelings, Bastiaan W.
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.
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Gorski, Mathias ; Jung, Bettina ; Li, Yong ; Matias-Garcia, Pamela R. ; Wuttke, Matthias ; Coassin, Stefan ; Thio, Chris H. L. ; Kleber, Marcus E. ; Winkler, Thomas W. ; Wanner, Veronika ; Chai, Jin-Fang ; Chu, Audrey Y. ; Cocca, Massimiliano ; Feitosa, Mary F. ; Ghasemi, Sahar ; Hoppmann, Anselm ; Horn, Katrin ; Li, Man ; Nutile, Teresa ; Scholz, Markus ; Sieber, Karsten B. ; Teumer, Alexander ; Tin, Adrienne ; Wang, Judy ; Tayo, Bamidele O. ; Ahluwalia, Tarunveer S. ; Almgren, Peter ; Bakker, Stephan J. L. ; Banas, Bernhard ; Bansal, Nisha ; Biggs, Mary L. ; Boerwinkle, Eric ; Böttinger, Erwin ; Brenner, Hermann ; Carroll, Robert J. ; Chalmers, John ; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Coresh, Josef ; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Franke, Andre ; Freitag-Wolf, Sandra ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen ; Gieger, Christian ; Hamet, Pavel ; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Foo, Valencia Hui Xian ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Kahonen, Mika ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Kraemer, Bernhard K. ; Kuehnel, Brigitte ; Lange, Leslie A. ; Lehtimaki, Terho ; Lieb, Wolfgang ; Loos, Ruth J. F. ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P. ; Mononen, Nina ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; O'Donoghue, Michelle L. ; Orho-Melander, Marju ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome ; Sabanayagam, Charumathi ; Schmidt, Helena ; Schmidt, Reinhold ; Schoettker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz ; Shaffer, Christian M. ; Strauch, Konstantin ; Szymczak, Silke ; Taylor, Kent D. ; Tremblay, Johanne ; Chaker, Layal ; van der Harst, Pim ; van der Most, Peter J. ; Verweij, Niek ; Voelker, Uwe ; Waldenberger, Melanie ; Wallentin, Lars ; Waterworth, Dawn M. ; White, Harvey D. ; Wilson, James G. ; Wong, Tien-Yin ; Woodward, Mark ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Yan ; Snieder, Harold ; Wanner, Christoph ; Boger, Carsten A. ; Kottgen, Anna ; Kronenberg, Florian ; Pattaro, Cristian ; Heid, Iris M.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.