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 - Schmidt, Marco F. A1 - Korb, Oliver A1 - Abell, Chris T1 - Antagonists of the miRNA-Argonaute 2 Protein Complex BT - Anti-miR-AGOs JF - Drug Target miRNA: Methods and Protocols N2 - microRNAs (miRNAs) have been identified as high-value drug targets. A widely applied strategy in miRNA inhibition is the use of antisense agents. However, it has been shown that oligonucleotides are poorly cell permeable because of their complex chemical structure and due to their negatively charged backbone. Consequently, the general application of oligonucleotides in therapy is limited. Since miRNAs’ functions are executed exclusively by the Argonaute 2 protein, we therefore describe a protocol for the design of a novel miRNA inhibitor class: antagonists of the miRNA-Argonaute 2 protein complex, so-called anti-miR-AGOs, that not only block the crucial binding site of the target miRNA but also bind to the protein’s active site. Due to their lower molecular weight and, thus, more drug-like chemical structure, the novel inhibitor class may show better pharmacokinetic properties than reported oligonucleotide inhibitors, enabling them for potential therapeutic use. KW - Drug design KW - microRNA KW - miRNA-Argonaute 2 protein complex KW - miRNA inhibitors KW - miRNA seed region Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 SN - 978-1-4939-8236-3 U6 - https://doi.org/10.1007/978-1-4939-6563-2_17 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - 239 EP - 249 PB - Springer CY - New York ER - TY - JOUR A1 - Schmidt, Marco F. T1 - miRNA Targeting Drugs BT - the next blockbusters? JF - Drug Target miRNA: Methods and Protocols N2 - Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. Addressing miRNAs as drug targets may enable the cure, or at least the treatment of diseases, which presently seems impossible. However, due to miRNAs’ chemical structure, generation of potential drug molecules with necessary pharmacokinetic properties is still challenging and requires a re-thinking of the drug discovery process. Therefore, this chapter highlights the potential of miRNAs as drug targets, discusses the challenges, and tries to give a complete overview of recent strategies in miRNA drug discovery. KW - miRNA KW - Drug discovery KW - microRNA-induced silencing complex KW - Antisense agents KW - Small-molecule miRNA modulators KW - Argonaute 2 protein Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 U6 - https://doi.org/10.1007/978-1-4939-6563-2_1 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - 3 EP - 22 PB - Springer CY - New York ER - TY - CHAP A1 - Schmidt, Marco F. ED - Schmidt, Marco F. T1 - Preface T2 - Drug target miRNA Y1 - 2016 SN - 978-1-4939-6563-2 SN - 978-1-4939-6561-8 U6 - https://doi.org/10.1007/978-1-4939-6563-2 SN - 1064-3745 SN - 1940-6029 VL - 1517 SP - V EP - V PB - Springer CY - New York ER - TY - JOUR A1 - Tucker, Marlee A. A1 - Boehning-Gaese, Katrin A1 - Fagan, William F. A1 - Fryxell, John M. A1 - Van Moorter, Bram A1 - Alberts, Susan C. A1 - Ali, Abdullahi H. A1 - Allen, Andrew M. A1 - Attias, Nina A1 - Avgar, Tal A1 - Bartlam-Brooks, Hattie A1 - Bayarbaatar, Buuveibaatar A1 - Belant, Jerrold L. A1 - Bertassoni, Alessandra A1 - Beyer, Dean A1 - Bidner, Laura A1 - van Beest, Floris M. A1 - Blake, Stephen A1 - Blaum, Niels A1 - Bracis, Chloe A1 - Brown, Danielle A1 - de Bruyn, P. J. Nico A1 - Cagnacci, Francesca A1 - Calabrese, Justin M. A1 - Camilo-Alves, Constanca A1 - Chamaille-Jammes, Simon A1 - Chiaradia, Andre A1 - Davidson, Sarah C. A1 - Dennis, Todd A1 - DeStefano, Stephen A1 - Diefenbach, Duane A1 - Douglas-Hamilton, Iain A1 - Fennessy, Julian A1 - Fichtel, Claudia A1 - Fiedler, Wolfgang A1 - Fischer, Christina A1 - Fischhoff, Ilya A1 - Fleming, Christen H. A1 - Ford, Adam T. A1 - Fritz, Susanne A. A1 - Gehr, Benedikt A1 - Goheen, Jacob R. A1 - Gurarie, Eliezer A1 - Hebblewhite, Mark A1 - Heurich, Marco A1 - Hewison, A. J. Mark A1 - Hof, Christian A1 - Hurme, Edward A1 - Isbell, Lynne A. A1 - Janssen, Rene A1 - Jeltsch, Florian A1 - Kaczensky, Petra A1 - Kane, Adam A1 - Kappeler, Peter M. A1 - Kauffman, Matthew A1 - Kays, Roland A1 - Kimuyu, Duncan A1 - Koch, Flavia A1 - Kranstauber, Bart A1 - LaPoint, Scott A1 - Leimgruber, Peter A1 - Linnell, John D. C. A1 - Lopez-Lopez, Pascual A1 - Markham, A. Catherine A1 - Mattisson, Jenny A1 - Medici, Emilia Patricia A1 - Mellone, Ugo A1 - Merrill, Evelyn A1 - Mourao, Guilherme de Miranda A1 - Morato, Ronaldo G. A1 - Morellet, Nicolas A1 - Morrison, Thomas A. A1 - Diaz-Munoz, Samuel L. A1 - Mysterud, Atle A1 - Nandintsetseg, Dejid A1 - Nathan, Ran A1 - Niamir, Aidin A1 - Odden, John A1 - Oliveira-Santos, Luiz Gustavo R. A1 - Olson, Kirk A. A1 - Patterson, Bruce D. A1 - de Paula, Rogerio Cunha A1 - Pedrotti, Luca A1 - Reineking, Bjorn A1 - Rimmler, Martin A1 - Rogers, Tracey L. A1 - Rolandsen, Christer Moe A1 - Rosenberry, Christopher S. A1 - Rubenstein, Daniel I. A1 - Safi, Kamran A1 - Said, Sonia A1 - Sapir, Nir A1 - Sawyer, Hall A1 - Schmidt, Niels Martin A1 - Selva, Nuria A1 - Sergiel, Agnieszka A1 - Shiilegdamba, Enkhtuvshin A1 - Silva, Joao Paulo A1 - Singh, Navinder A1 - Solberg, Erling J. A1 - Spiegel, Orr A1 - Strand, Olav A1 - Sundaresan, Siva A1 - Ullmann, Wiebke A1 - Voigt, Ulrich A1 - Wall, Jake A1 - Wattles, David A1 - Wikelski, Martin A1 - Wilmers, Christopher C. A1 - Wilson, John W. A1 - Wittemyer, George A1 - Zieba, Filip A1 - Zwijacz-Kozica, Tomasz A1 - Mueller, Thomas T1 - Moving in the Anthropocene BT - global reductions in terrestrial mammalian movements JF - Science N2 - Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission. Y1 - 2018 U6 - https://doi.org/10.1126/science.aam9712 SN - 0036-8075 SN - 1095-9203 VL - 359 IS - 6374 SP - 466 EP - 469 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Cope, Justin L. A1 - Baukmann, Hannes A. A1 - Klinger, Jörn E. A1 - Ravarani, Charles N. J. A1 - Böttinger, Erwin A1 - Konigorski, Stefan A1 - Schmidt, Marco F. T1 - Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status JF - Frontiers in genetics N2 - Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson's Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson's disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem. KW - epistasis KW - machine learning KW - feature selection KW - parkinson's disease KW - PPMI (parkinson's progression markers initiative) Y1 - 2021 U6 - https://doi.org/10.3389/fgene.2021.744557 SN - 1664-8021 VL - 12 PB - Frontiers Media CY - Lausanne ER -