TY - JOUR A1 - Yang, Fang A1 - Lai, Xinlong A1 - Deng, Li A1 - Liu, Xiaoxiao A1 - Li, Jian A1 - Zeng, Shuixiu A1 - Zhang, Cheng A1 - Hocher, Carl-Friedrich A1 - Hocher, Berthold T1 - Association of endothelin-1 gene polymorphisms with the clinical phenotype in primary nephrotic syndrome of children JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims:This study aims to investigate the relationship between plasma endothelin-1 (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A and clinical features of primary nephrotic syndrome (NS) in children. Materials and methods: Thirty-six children with primary NS were selected as case group, and 94 healthy children were selected as control group. All subjects were genotyped for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A) and rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using a radio-immunoassay. Key findings: Plasma ET-1 concentrations were higher in NS patients (P = 0.007) as compared to healthy children. The allele frequencies between control and NS patients were significantly different only with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies between control and NS patients for the rs5370 SNP showed a trend towards difference (P = 0.057). Plasma cholesterol in NS patients is associated with both: the Cl genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P < 0.05 in both cases). Significance: The ET systems might play a disease modifying role in pediatric NS. Plasma cholesterol, a hallmark of NS. seems to be associated with genetic variations within the human ET-1 gene. (C) 2014 Elsevier Inc. All rights reserved. KW - Endothelin-1 KW - Gene polymorphism KW - Childhood nephrotic syndrome KW - Cholesterol Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2014.04.010 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 446 EP - 450 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Zhang, Shengrui A1 - Xu, Qinghai A1 - Gaillard, Marie-Jose A1 - Cao, Xianyong A1 - Li, Jianyong A1 - Zhang, Liyan A1 - Li, Yuecong A1 - Tian, Fang A1 - Zhou, Liping A1 - Lin, Fengyou A1 - Yang, Xiaolan T1 - Characteristic pollen source area and vertical pollen dispersal and deposition in a mixed coniferous and deciduous broad-leaved woodland in the Changbai mountains, northeast China JF - Vegetation History and Archaeobotany N2 - Pollen influx (number of pollen grains cm−2 year−1) can objectively reflect the dispersal and deposition features of pollen within a certain time and space, and is often used as a basis for the quantitative reconstruction of palaeovegetation; however, little is known about the features and mechanisms of vertical dispersal of pollen. Here we present the results from a 5 year (2006–2010) monitoring program using pollen traps placed at different heights from ground level up to 60 m and surface soil samples in a mixed coniferous and deciduous broad-leaved woodland in the Changbai mountains, northeastern China. The pollen percentages and pollen influx from the traps have very similar characteristics to the highest values for Betula, Fraxinus, Quercus and Pinus, among the tree taxa and Artemisia, Chenopodiaceae and Asteraceae among the herb taxa. Pollen influx values vary significantly with height and show major differences between three distinct layers, above-canopy (≥32 m), within the trunk layer (8 ≤ 32 m) and on the ground (0 m). These differences in pollen influx are explained by differences in (i) the air flows in each of these layers and (ii) the fall speed of pollen of the various taxa. We found that the pollen recorded on the ground surface is a good representation of the major part of the pollen transported in the trunk space of the woodland. Comparison of the pollen influx values with the theoretical, calculated “characteristic pollen source area” (CPSA) of 12 selected taxa indicates that the pollen deposited on the ground surface of the woodland is a fair representation with 85–90 % of the total pollen deposited at a wind speed of 2.4 m s−1 coming from within ca. 1–5 km for Pinus and Quercus, ca. 5–10 km for Ulmus, Tilia, Oleaceae and Betula, ca. 20–40 km for Fraxinus, Poaceae, Chenopodiaceae, Populus and Salix, and ca. 30–60 km for Artemisia; it is also a good representation with 90–98 % of the total pollen deposited coming from within 60 km at a wind speed of 2.4 m s−1, or 100 km at a wind speed: 6 m s−1, for the 12 selected taxa used in the CPSA calculation. Furthermore, comparison with the vegetation map of the area around the sampling site shows that the pollen deposited on the ground represents all plant communities which grow in the study area within 70 km radius of the sampling site. In this study, the pollen percentages obtained from the soil surface samples are significantly biased towards pollen taxa with good preservation due to thick and robust pollen walls. Therefore, if mosses are available instead, soil samples should be avoided for pollen studies, in particular for the study of pollen-vegetation relationships, the estimation of pollen productivities and quantitative reconstruction of past vegetation. The results also indicate that the existing model of pollen dispersal and deposition, Prentice’s model, provides a fair description of the actual pollen dispersal and deposition in this kind of woodland, which suggests that the application of the landscape reconstruction algorithm would be relevant for reconstruction of this type of woodland in the past. KW - Changbai mountains KW - Mixed coniferous and deciduous broad-leaved woodland KW - Vertical pollen dispersal and deposition KW - Characteristic pollen source area Y1 - 2016 U6 - https://doi.org/10.1007/s00334-015-0532-0 SN - 0939-6314 SN - 1617-6278 VL - 25 SP - 29 EP - 43 PB - Springer CY - New York ER - TY - JOUR A1 - Zhou, Ying A1 - Zhang, Ling A1 - Gui, Jiadong A1 - Dong, Fang A1 - Cheng, Sihua A1 - Mei, Xin A1 - Zhang, Linyun A1 - Li, Yongqing A1 - Su, Xinguo A1 - Baldermann, Susanne A1 - Watanabe, Naoharu A1 - Yang, Ziyin T1 - Molecular Cloning and Characterization of a Short-Chain Dehydrogenase Showing Activity with Volatile Compounds Isolated from Camellia sinensis JF - Plant molecular biology reporter N2 - Camellia sinensis synthesizes and emits a large variety of volatile phenylpropanoids and benzenoids (VPB). To investigate the enzymes involved in the formation of these VPB compounds, a new C. sinensis short-chain dehydrogenase/reductase (CsSDR) was isolated, cloned, sequenced, and functionally characterized. The complete open reading frame of CsSDR contains 996 nucleotides with a calculated protein molecular mass of 34.5 kDa. The CsSDR recombinant protein produced in Escherichia coli exhibited dehydrogenase-reductase activity towards several major VPB compounds in C. sinensis flowers with a strong preference for NADP/NADPH co-factors, and showed affinity for (R)/(S)-1-phenylethanol (1PE), phenylacetaldehyde, benzaldehyde, and benzyl alcohol, and no affinity for acetophenone (AP) and 2-phenylethanol. CsSDR showed the highest catalytic efficiency towards (R)/(S)-1PE. Furthermore, the transient expression analysis in Nicotiana benthamiana plants validated that CsSDR could convert 1PE to AP in plants. CsSDR transcript level was not significantly affected by floral development and some jasmonic acid-related environmental stress, and CsSDR transcript accumulation was detected in most floral tissues such as receptacle and anther, which were main storage locations of VPB compounds. Our results indicate that CsSDR is expressed in C. sinensis flowers and is likely to contribute to a number of floral VPB compounds including the 1PE derivative AP. KW - Camellia sinensis KW - 1-Phenylethanol KW - Phenylpropanoids KW - Short chain dehydrogenase KW - Volatile compound Y1 - 2015 U6 - https://doi.org/10.1007/s11105-014-0751-z SN - 0735-9640 SN - 1572-9818 VL - 33 IS - 2 SP - 253 EP - 263 PB - Springer CY - New York ER - TY - JOUR A1 - Herzschuh, Ulrike A1 - Cao, Xianyong A1 - Laepple, Thomas A1 - Dallmeyer, Anne A1 - Telford, Richard J. A1 - Ni, Jian A1 - Chen, Fahu A1 - Kong, Zhaochen A1 - Liu, Guangxiu A1 - Liu, Kam-Biu A1 - Liu, Xingqi A1 - Stebich, Martina A1 - Tang, Lingyu A1 - Tian, Fang A1 - Wang, Yongbo A1 - Wischnewski, Juliane A1 - Xu, Qinghai A1 - Yan, Shun A1 - Yang, Zhenjing A1 - Yu, Ge A1 - Zhang, Yun A1 - Zhao, Yan A1 - Zheng, Zhuo T1 - Position and orientation of the westerly jet determined Holocene rainfall patterns in China JF - Nature Communications N2 - Proxy-based reconstructions and modeling of Holocene spatiotemporal precipitation patterns for China and Mongolia have hitherto yielded contradictory results indicating that the basic mechanisms behind the East Asian Summer Monsoon and its interaction with the westerly jet stream remain poorly understood. We present quantitative reconstructions of Holocene precipitation derived from 101 fossil pollen records and analyse them with the help of a minimal empirical model. We show that the westerly jet-stream axis shifted gradually southward and became less tilted since the middle Holocene. This was tracked by the summer monsoon rain band resulting in an early-Holocene precipitation maximum over most of western China, a mid-Holocene maximum in north-central and northeastern China, and a late-Holocene maximum in southeastern China. Our results suggest that a correct simulation of the orientation and position of the westerly jet stream is crucial to the reliable prediction of precipitation patterns in China and Mongolia. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-09866-8 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Jia, Weihan A1 - Anslan, Sten A1 - Chen, Fahu A1 - Cao, Xianyong A1 - Dong, Hailiang A1 - Dulias, Katharina A1 - Gu, Zhengquan A1 - Heinecke, Liv A1 - Jiang, Hongchen A1 - Kruse, Stefan A1 - Kang, Wengang A1 - Li, Kai A1 - Liu, Sisi A1 - Liu, Xingqi A1 - Liu, Ying A1 - Ni, Jian A1 - Schwalb, Antje A1 - Stoof-Leichsenring, Kathleen R. A1 - Shen, Wei A1 - Tian, Fang A1 - Wang, Jing A1 - Wang, Yongbo A1 - Wang, Yucheng A1 - Xu, Hai A1 - Yang, Xiaoyan A1 - Zhang, Dongju A1 - Herzschuh, Ulrike T1 - Sedimentary ancient DNA reveals past ecosystem and biodiversity changes on the Tibetan Plateau: overview and prospects JF - Quaternary science reviews : the international multidisciplinary research and review journal N2 - Alpine ecosystems on the Tibetan Plateau are being threatened by ongoing climate warming and intensified human activities. Ecological time-series obtained from sedimentary ancient DNA (sedaDNA) are essential for understanding past ecosystem and biodiversity dynamics on the Tibetan Plateau and their responses to climate change at a high taxonomic resolution. Hitherto only few but promising studies have been published on this topic. The potential and limitations of using sedaDNA on the Tibetan Plateau are not fully understood. Here, we (i) provide updated knowledge of and a brief introduction to the suitable archives, region-specific taphonomy, state-of-the-art methodologies, and research questions of sedaDNA on the Tibetan Plateau; (ii) review published and ongoing sedaDNA studies from the Tibetan Plateau; and (iii) give some recommendations for future sedaDNA study designs. Based on the current knowledge of taphonomy, we infer that deep glacial lakes with freshwater and high clay sediment input, such as those from the southern and southeastern Tibetan Plateau, may have a high potential for sedaDNA studies. Metabarcoding (for microorganisms and plants), metagenomics (for ecosystems), and hybridization capture (for prehistoric humans) are three primary sedaDNA approaches which have been successfully applied on the Tibetan Plateau, but their power is still limited by several technical issues, such as PCR bias and incompleteness of taxonomic reference databases. Setting up high-quality and open-access regional taxonomic reference databases for the Tibetan Plateau should be given priority in the future. To conclude, the archival, taphonomic, and methodological conditions of the Tibetan Plateau are favorable for performing sedaDNA studies. More research should be encouraged to address questions about long-term ecological dynamics at ecosystem scale and to bring the paleoecology of the Tibetan Plateau into a new era. KW - Sedimentary ancient DNA (sedaDNA) KW - Tibetan Plateau KW - Environmental DNA KW - Taphonomy KW - Ecosystem KW - Biodiversity KW - Paleoecology KW - Paleogeography Y1 - 2022 U6 - https://doi.org/10.1016/j.quascirev.2022.107703 SN - 0277-3791 SN - 1873-457X VL - 293 PB - Elsevier CY - Oxford ER - TY - GEN A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 19 KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-565379 IS - 19 ER - TY - JOUR A1 - Wuttke, Matthias A1 - Li, Yong A1 - Li, Man A1 - Sieber, Karsten B. A1 - Feitosa, Mary F. A1 - Gorski, Mathias A1 - Tin, Adrienne A1 - Wang, Lihua A1 - Chu, Audrey Y. A1 - Hoppmann, Anselm A1 - Kirsten, Holger A1 - Giri, Ayush A1 - Chai, Jin-Fang A1 - Sveinbjornsson, Gardar A1 - Tayo, Bamidele O. A1 - Nutile, Teresa A1 - Fuchsberger, Christian A1 - Marten, Jonathan A1 - Cocca, Massimiliano A1 - Ghasemi, Sahar A1 - Xu, Yizhe A1 - Horn, Katrin A1 - Noce, Damia A1 - Van der Most, Peter J. A1 - Sedaghat, Sanaz A1 - Yu, Zhi A1 - Akiyama, Masato A1 - Afaq, Saima A1 - Ahluwalia, Tarunveer Singh A1 - Almgren, Peter A1 - Amin, Najaf A1 - Arnlov, Johan A1 - Bakker, Stephan J. L. A1 - Bansal, Nisha A1 - Baptista, Daniela A1 - Bergmann, Sven A1 - Biggs, Mary L. A1 - Biino, Ginevra A1 - Boehnke, Michael A1 - Boerwinkle, Eric A1 - Boissel, Mathilde A1 - Böttinger, Erwin A1 - Boutin, Thibaud S. A1 - Brenner, Hermann A1 - Brumat, Marco A1 - Burkhardt, Ralph A1 - Butterworth, Adam S. A1 - Campana, Eric A1 - Campbell, Archie A1 - Campbell, Harry A1 - Canouil, Mickael A1 - Carroll, Robert J. A1 - Catamo, Eulalia A1 - Chambers, John C. A1 - Chee, Miao-Ling A1 - Chee, Miao-Li A1 - Chen, Xu A1 - Cheng, Ching-Yu A1 - Cheng, Yurong A1 - Christensen, Kaare A1 - Cifkova, Renata A1 - Ciullo, Marina A1 - Concas, Maria Pina A1 - Cook, James P. A1 - Coresh, Josef A1 - Corre, Tanguy A1 - Sala, Cinzia Felicita A1 - Cusi, Daniele A1 - Danesh, John A1 - Daw, E. Warwick A1 - De Borst, Martin H. A1 - De Grandi, Alessandro A1 - De Mutsert, Renee A1 - De Vries, Aiko P. J. A1 - Degenhardt, Frauke A1 - Delgado, Graciela A1 - Demirkan, Ayse A1 - Di Angelantonio, Emanuele A1 - Dittrich, Katalin A1 - Divers, Jasmin A1 - Dorajoo, Rajkumar A1 - Eckardt, Kai-Uwe A1 - Ehret, Georg A1 - Elliott, Paul A1 - Endlich, Karlhans A1 - Evans, Michele K. A1 - Felix, Janine F. A1 - Foo, Valencia Hui Xian A1 - Franco, Oscar H. A1 - Franke, Andre A1 - Freedman, Barry I. A1 - Freitag-Wolf, Sandra A1 - Friedlander, Yechiel A1 - Froguel, Philippe A1 - Gansevoort, Ron T. A1 - Gao, He A1 - Gasparini, Paolo A1 - Gaziano, J. Michael A1 - Giedraitis, Vilmantas A1 - Gieger, Christian A1 - Girotto, Giorgia A1 - Giulianini, Franco A1 - Gogele, Martin A1 - Gordon, Scott D. A1 - Gudbjartsson, Daniel F. A1 - Gudnason, Vilmundur A1 - Haller, Toomas A1 - Hamet, Pavel A1 - Harris, Tamara B. A1 - Hartman, Catharina A. A1 - Hayward, Caroline A1 - Hellwege, Jacklyn N. A1 - Heng, Chew-Kiat A1 - Hicks, Andrew A. A1 - Hofer, Edith A1 - Huang, Wei A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Indridason, Olafur S. A1 - Ingelsson, Erik A1 - Ising, Marcus A1 - Jaddoe, Vincent W. V. A1 - Jakobsdottir, Johanna A1 - Jonas, Jost B. A1 - Joshi, Peter K. A1 - Josyula, Navya Shilpa A1 - Jung, Bettina A1 - Kahonen, Mika A1 - Kamatani, Yoichiro A1 - Kammerer, Candace M. A1 - Kanai, Masahiro A1 - Kastarinen, Mika A1 - Kerr, Shona M. A1 - Khor, Chiea-Chuen A1 - Kiess, Wieland A1 - Kleber, Marcus E. A1 - Koenig, Wolfgang A1 - Kooner, Jaspal S. A1 - Korner, Antje A1 - Kovacs, Peter A1 - Kraja, Aldi T. A1 - Krajcoviechova, Alena A1 - Kramer, Holly A1 - Kramer, Bernhard K. A1 - Kronenberg, Florian A1 - Kubo, Michiaki A1 - Kuhnel, Brigitte A1 - Kuokkanen, Mikko A1 - Kuusisto, Johanna A1 - La Bianca, Martina A1 - Laakso, Markku A1 - Lange, Leslie A. A1 - Langefeld, Carl D. A1 - Lee, Jeannette Jen-Mai A1 - Lehne, Benjamin A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Lim, Su-Chi A1 - Lind, Lars A1 - Lindgren, Cecilia M. A1 - Liu, Jun A1 - Liu, Jianjun A1 - Loeffler, Markus A1 - Loos, Ruth J. F. A1 - Lucae, Susanne A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Magi, Reedik A1 - Magnusson, Patrik K. E. A1 - Mahajan, Anubha A1 - Martin, Nicholas G. A1 - Martins, Jade A1 - Marz, Winfried A1 - Mascalzoni, Deborah A1 - Matsuda, Koichi A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Metspalu, Andres A1 - Mikaelsdottir, Evgenia K. A1 - Milaneschi, Yuri A1 - Miliku, Kozeta A1 - Mishra, Pashupati P. A1 - Program, V. A. Million Veteran A1 - Mohlke, Karen L. A1 - Mononen, Nina A1 - Montgomery, Grant W. A1 - Mook-Kanamori, Dennis O. A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nalls, Mike A. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - Noordam, Raymond A1 - Olafsson, Isleifur A1 - Oldehinkel, Albertine J. A1 - Orho-Melander, Marju A1 - Ouwehand, Willem H. A1 - Padmanabhan, Sandosh A1 - Palmer, Nicholette D. A1 - Palsson, Runolfur A1 - Penninx, Brenda W. J. H. A1 - Perls, Thomas A1 - Perola, Markus A1 - Pirastu, Mario A1 - Pirastu, Nicola A1 - Pistis, Giorgio A1 - Podgornaia, Anna I. A1 - Polasek, Ozren A1 - Ponte, Belen A1 - Porteous, David J. A1 - Poulain, Tanja A1 - Pramstaller, Peter P. A1 - Preuss, Michael H. A1 - Prins, Bram P. A1 - Province, Michael A. A1 - Rabelink, Ton J. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Reilly, Dermot F. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Ridker, Paul M. A1 - Rivadeneira, Fernando A1 - Rizzi, Federica A1 - Roberts, David J. A1 - Robino, Antonietta A1 - Rossing, Peter A1 - Rudan, Igor A1 - Rueedi, Rico A1 - Ruggiero, Daniela A1 - Ryan, Kathleen A. A1 - Saba, Yasaman A1 - Sabanayagam, Charumathi A1 - Salomaa, Veikko A1 - Salvi, Erika A1 - Saum, Kai-Uwe A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Ben Schottker, A1 - Schulz, Christina-Alexandra A1 - Schupf, Nicole A1 - Shaffer, Christian M. A1 - Shi, Yuan A1 - Smith, Albert V. A1 - Smith, Blair H. A1 - Soranzo, Nicole A1 - Spracklen, Cassandra N. A1 - Strauch, Konstantin A1 - Stringham, Heather M. A1 - Stumvoll, Michael A1 - Svensson, Per O. A1 - Szymczak, Silke A1 - Tai, E-Shyong A1 - Tajuddin, Salman M. A1 - Tan, Nicholas Y. Q. A1 - Taylor, Kent D. A1 - Teren, Andrej A1 - Tham, Yih-Chung A1 - Thiery, Joachim A1 - Thio, Chris H. L. A1 - Thomsen, Hauke A1 - Thorleifsson, Gudmar A1 - Toniolo, Daniela A1 - Tonjes, Anke A1 - Tremblay, Johanne A1 - Tzoulaki, Ioanna A1 - Uitterlinden, Andre G. A1 - Vaccargiu, Simona A1 - Van Dam, Rob M. A1 - Van der Harst, Pim A1 - Van Duijn, Cornelia M. A1 - Edward, Digna R. Velez A1 - Verweij, Niek A1 - Vogelezang, Suzanne A1 - Volker, Uwe A1 - Vollenweider, Peter A1 - Waeber, Gerard A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Wang, Ya Xing A1 - Wang, Chaolong A1 - Waterworth, Dawn M. A1 - Bin Wei, Wen A1 - White, Harvey A1 - Whitfield, John B. A1 - Wild, Sarah H. A1 - Wilson, James F. A1 - Wojczynski, Mary K. A1 - Wong, Charlene A1 - Wong, Tien-Yin A1 - Xu, Liang A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Weihua A1 - Zonderman, Alan B. A1 - Rotter, Jerome I. A1 - Bochud, Murielle A1 - Psaty, Bruce M. A1 - Vitart, Veronique A1 - Wilson, James G. A1 - Dehghan, Abbas A1 - Parsa, Afshin A1 - Chasman, Daniel I. A1 - Ho, Kevin A1 - Morris, Andrew P. A1 - Devuyst, Olivier A1 - Akilesh, Shreeram A1 - Pendergrass, Sarah A. A1 - Sim, Xueling A1 - Boger, Carsten A. A1 - Okada, Yukinori A1 - Edwards, Todd L. A1 - Snieder, Harold A1 - Stefansson, Kari A1 - Hung, Adriana M. A1 - Heid, Iris M. A1 - Scholz, Markus A1 - Teumer, Alexander A1 - Kottgen, Anna A1 - Pattaro, Cristian T1 - A catalog of genetic loci associated with kidney function from analyses of a million individuals JF - Nature genetics N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1038/s41588-019-0407-x SN - 1061-4036 SN - 1546-1718 VL - 51 IS - 6 SP - 957 EP - + PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline JF - Kidney international : official journal of the International Society of Nephrology N2 - 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. KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - https://doi.org/10.1016/j.kint.2020.09.030 SN - 0085-2538 SN - 1523-1755 VL - 99 IS - 4 SP - 926 EP - 939 PB - Elsevier CY - New York ER -