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Language
- English (13)
Is part of the Bibliography
- yes (13)
Keywords
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Wuttke, Matthias ; Li, Yong ; Li, Man ; Sieber, Karsten B. ; Feitosa, Mary F. ; Gorski, Mathias ; Tin, Adrienne ; Wang, Lihua ; Chu, Audrey Y. ; Hoppmann, Anselm ; Kirsten, Holger ; Giri, Ayush ; Chai, Jin-Fang ; Sveinbjornsson, Gardar ; Tayo, Bamidele O. ; Nutile, Teresa ; Fuchsberger, Christian ; Marten, Jonathan ; Cocca, Massimiliano ; Ghasemi, Sahar ; Xu, Yizhe ; Horn, Katrin ; Noce, Damia ; Van der Most, Peter J. ; Sedaghat, Sanaz ; Yu, Zhi ; Akiyama, Masato ; Afaq, Saima ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Amin, Najaf ; Arnlov, Johan ; Bakker, Stephan J. L. ; Bansal, Nisha ; Baptista, Daniela ; Bergmann, Sven ; Biggs, Mary L. ; Biino, Ginevra ; Boehnke, Michael ; Boerwinkle, Eric ; Boissel, Mathilde ; Böttinger, Erwin ; Boutin, Thibaud S. ; Brenner, Hermann ; Brumat, Marco ; Burkhardt, Ralph ; Butterworth, Adam S. ; Campana, Eric ; Campbell, Archie ; Campbell, Harry ; Canouil, Mickael ; Carroll, Robert J. ; Catamo, Eulalia ; Chambers, John C. ; Chee, Miao-Ling ; Chee, Miao-Li ; Chen, Xu ; Cheng, Ching-Yu ; Cheng, Yurong ; Christensen, Kaare ; Cifkova, Renata ; Ciullo, Marina ; Concas, Maria Pina ; Cook, James P. ; Coresh, Josef ; Corre, Tanguy ; Sala, Cinzia Felicita ; Cusi, Daniele ; Danesh, John ; Daw, E. Warwick ; De Borst, Martin H. ; De Grandi, Alessandro ; De Mutsert, Renee ; De Vries, Aiko P. J. ; Degenhardt, Frauke ; Delgado, Graciela ; Demirkan, Ayse ; Di Angelantonio, Emanuele ; Dittrich, Katalin ; Divers, Jasmin ; Dorajoo, Rajkumar ; Eckardt, Kai-Uwe ; Ehret, Georg ; Elliott, Paul ; Endlich, Karlhans ; Evans, Michele K. ; Felix, Janine F. ; Foo, Valencia Hui Xian ; Franco, Oscar H. ; Franke, Andre ; Freedman, Barry I. ; Freitag-Wolf, Sandra ; Friedlander, Yechiel ; Froguel, Philippe ; Gansevoort, Ron T. ; Gao, He ; Gasparini, Paolo ; Gaziano, J. Michael ; Giedraitis, Vilmantas ; Gieger, Christian ; Girotto, Giorgia ; Giulianini, Franco ; Gogele, Martin ; Gordon, Scott D. ; Gudbjartsson, Daniel F. ; Gudnason, Vilmundur ; Haller, Toomas ; Hamet, Pavel ; Harris, Tamara B. ; Hartman, Catharina A. ; Hayward, Caroline ; Hellwege, Jacklyn N. ; Heng, Chew-Kiat ; Hicks, Andrew A. ; Hofer, Edith ; Huang, Wei ; Hutri-Kahonen, Nina ; Hwang, Shih-Jen ; Ikram, M. Arfan ; Indridason, Olafur S. ; Ingelsson, Erik ; Ising, Marcus ; Jaddoe, Vincent W. V. ; Jakobsdottir, Johanna ; Jonas, Jost B. ; Joshi, Peter K. ; Josyula, Navya Shilpa ; Jung, Bettina ; Kahonen, Mika ; Kamatani, Yoichiro ; Kammerer, Candace M. ; Kanai, Masahiro ; Kastarinen, Mika ; Kerr, Shona M. ; Khor, Chiea-Chuen ; Kiess, Wieland ; Kleber, Marcus E. ; Koenig, Wolfgang ; Kooner, Jaspal S. ; Korner, Antje ; Kovacs, Peter ; Kraja, Aldi T. ; Krajcoviechova, Alena ; Kramer, Holly ; Kramer, Bernhard K. ; Kronenberg, Florian ; Kubo, Michiaki ; Kuhnel, Brigitte ; Kuokkanen, Mikko ; Kuusisto, Johanna ; La Bianca, Martina ; Laakso, Markku ; Lange, Leslie A. ; Langefeld, Carl D. ; Lee, Jeannette Jen-Mai ; Lehne, Benjamin ; Lehtimaki, Terho ; Lieb, Wolfgang ; Lim, Su-Chi ; Lind, Lars ; Lindgren, Cecilia M. ; Liu, Jun ; Liu, Jianjun ; Loeffler, Markus ; Loos, Ruth J. F. ; Lucae, Susanne ; Lukas, Mary Ann ; Lyytikainen, Leo-Pekka ; Magi, Reedik ; Magnusson, Patrik K. E. ; Mahajan, Anubha ; Martin, Nicholas G. ; Martins, Jade ; Marz, Winfried ; Mascalzoni, Deborah ; Matsuda, Koichi ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Metspalu, Andres ; Mikaelsdottir, Evgenia K. ; Milaneschi, Yuri ; Miliku, Kozeta ; Mishra, Pashupati P. ; Program, V. A. Million Veteran ; Mohlke, Karen L. ; Mononen, Nina ; Montgomery, Grant W. ; Mook-Kanamori, Dennis O. ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Nalls, Mike A. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; Noordam, Raymond ; Olafsson, Isleifur ; Oldehinkel, Albertine J. ; Orho-Melander, Marju ; Ouwehand, Willem H. ; Padmanabhan, Sandosh ; Palmer, Nicholette D. ; Palsson, Runolfur ; Penninx, Brenda W. J. H. ; Perls, Thomas ; Perola, Markus ; Pirastu, Mario ; Pirastu, Nicola ; Pistis, Giorgio ; Podgornaia, Anna I. ; Polasek, Ozren ; Ponte, Belen ; Porteous, David J. ; Poulain, Tanja ; Pramstaller, Peter P. ; Preuss, Michael H. ; Prins, Bram P. ; Province, Michael A. ; Rabelink, Ton J. ; Raffield, Laura M. ; Raitakari, Olli T. ; Reilly, Dermot F. ; Rettig, Rainer ; Rheinberger, Myriam ; Rice, Kenneth M. ; Ridker, Paul M. ; Rivadeneira, Fernando ; Rizzi, Federica ; Roberts, David J. ; Robino, Antonietta ; Rossing, Peter ; Rudan, Igor ; Rueedi, Rico ; Ruggiero, Daniela ; Ryan, Kathleen A. ; Saba, Yasaman ; Sabanayagam, Charumathi ; Salomaa, Veikko ; Salvi, Erika ; Saum, Kai-Uwe ; Schmidt, Helena ; Schmidt, Reinhold ; Ben Schottker ; Schulz, Christina-Alexandra ; Schupf, Nicole ; Shaffer, Christian M. ; Shi, Yuan ; Smith, Albert V. ; Smith, Blair H. ; Soranzo, Nicole ; Spracklen, Cassandra N. ; Strauch, Konstantin ; Stringham, Heather M. ; Stumvoll, Michael ; Svensson, Per O. ; Szymczak, Silke ; Tai, E-Shyong ; Tajuddin, Salman M. ; Tan, Nicholas Y. Q. ; Taylor, Kent D. ; Teren, Andrej ; Tham, Yih-Chung ; Thiery, Joachim ; Thio, Chris H. L. ; Thomsen, Hauke ; Thorleifsson, Gudmar ; Toniolo, Daniela ; Tonjes, Anke ; Tremblay, Johanne ; Tzoulaki, Ioanna ; Uitterlinden, Andre G. ; Vaccargiu, Simona ; Van Dam, Rob M. ; Van der Harst, Pim ; Van Duijn, Cornelia M. ; Edward, Digna R. Velez ; Verweij, Niek ; Vogelezang, Suzanne ; Volker, Uwe ; Vollenweider, Peter ; Waeber, Gerard ; Waldenberger, Melanie ; Wallentin, Lars ; Wang, Ya Xing ; Wang, Chaolong ; Waterworth, Dawn M. ; Bin Wei, Wen ; White, Harvey ; Whitfield, John B. ; Wild, Sarah H. ; Wilson, James F. ; Wojczynski, Mary K. ; Wong, Charlene ; Wong, Tien-Yin ; Xu, Liang ; Yang, Qiong ; Yasuda, Masayuki ; Yerges-Armstrong, Laura M. ; Zhang, Weihua ; Zonderman, Alan B. ; Rotter, Jerome I. ; Bochud, Murielle ; Psaty, Bruce M. ; Vitart, Veronique ; Wilson, James G. ; Dehghan, Abbas ; Parsa, Afshin ; Chasman, Daniel I. ; Ho, Kevin ; Morris, Andrew P. ; Devuyst, Olivier ; Akilesh, Shreeram ; Pendergrass, Sarah A. ; Sim, Xueling ; Boger, Carsten A. ; Okada, Yukinori ; Edwards, Todd L. ; Snieder, Harold ; Stefansson, Kari ; Hung, Adriana M. ; Heid, Iris M. ; Scholz, Markus ; Teumer, Alexander ; Kottgen, Anna ; Pattaro, Cristian
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.
VERITAS and Fermi-LAT Observations of TeV Gamma-Ray Sources Discovered by HAWC in the 2HWC Catalog
(2018)
Abeysekara, A. U. ; Archer, A. ; Benbow, Wystan ; Bird, Ralph ; Brose, Robert ; Buchovecky, M. ; Buckley, J. H. ; Bugaev, V. ; Chromey, A. J. ; Connolly, M. P. ; Cui, Wei ; Daniel, M. K. ; Falcone, A. ; Feng, Qi ; Finley, John P. ; Fortson, L. ; Furniss, Amy ; Huetten, M. ; Hanna, David ; Hervet, O. ; Holder, J. ; Hughes, G. ; Humensky, T. B. ; Johnson, Caitlin A. ; Kaaret, Philip ; Kar, P. ; Kertzman, M. ; Kieda, David ; Krause, M. ; Krennrich, F. ; Kumar, S. ; Lang, M. J. ; Lin, T. T. Y. ; McArthur, S. ; Moriarty, P. ; Mukherjee, Reshmi ; Ong, R. A. ; Otte, Adam Nepomuk ; Park, Nahee ; Petrashyk, A. ; Pohl, Martin ; Pueschel, Elisa ; Quinn, J. ; Ragan, K. ; Reynolds, P. T. ; Richards, Gregory T. ; Roache, E. ; Rulten, C. ; Sadeh, I. ; Santander, Marcos ; Sembroski, G. H. ; Shahinyan, Karlen ; Sushch, I. ; Tyler, J. ; Wakely, S. P. ; Weinstein, A. ; Wells, R. M. ; Wilcox, P. ; Wilhelm, Alina ; Williams, D. A. ; Williamson, T. J. ; Zitzer, B. ; Abdollahi, S. ; Ajello, Marco ; Baldini, Luca ; Barbiellini, G. ; Bastieri, Denis ; Bellazzini, Ronaldo ; Berenji, B. ; Bissaldi, Elisabetta ; Blandford, R. D. ; Bonino, R. ; Bottacini, E. ; Brandt, Terri J. ; Bruel, P. ; Buehler, R. ; Cameron, R. A. ; Caputo, R. ; Caraveo, P. A. ; Castro, D. ; Cavazzuti, E. ; Charles, Eric ; Chiaro, G. ; Ciprini, S. ; Cohen-Tanugi, Johann ; Costantin, D. ; Cutini, S. ; de Palma, F. ; Di Lalla, N. ; Di Mauro, M. ; Di Venere, L. ; Dominguez, A. ; Favuzzi, C. ; Fegan, S. J. ; Franckowiak, Anna ; Fukazawa, Yasushi ; Funk, Stefan ; Fusco, Piergiorgio ; Gargano, Fabio ; Gasparrini, Dario ; Giglietto, Nicola ; Giordano, F. ; Giroletti, Marcello ; Green, D. ; Grenier, I. A. ; Guillemot, L. ; Guiriec, Sylvain ; Hays, Elizabeth ; Hewitt, John W. ; Horan, D. ; Johannesson, G. ; Kensei, S. ; Kuss, M. ; Larsson, Stefan ; Latronico, L. ; Lemoine-Goumard, Marianne ; Li, J. ; Longo, Francesco ; Loparco, Francesco ; Lovellette, M. N. ; Lubrano, Pasquale ; Magill, Jeffrey D. ; Maldera, Simone ; Mazziotta, Mario Nicola ; McEnery, J. E. ; Michelson, P. F. ; Mitthumsiri, W. ; Mizuno, Tsunefumi ; Monzani, Maria Elena ; Morselli, Aldo ; Moskalenko, Igor V. ; Negro, M. ; Nuss, E. ; Ojha, R. ; Omodei, Nicola ; Orienti, M. ; Orlando, E. ; Palatiello, M. ; Paliya, Vaidehi S. ; Paneque, D. ; Perkins, Jeremy S. ; Persic, M. ; Pesce-Rollins, Melissa ; Petrosian, Vahe' ; Piron, F. ; Porter, Troy A. ; Principe, G. ; Raino, S. ; Rando, Riccardo ; Rani, B. ; Razzano, Massimilano ; Razzaque, Soebur ; Reimer, A. ; Reimer, Olaf ; Reposeur, T. ; Sgro, C. ; Siskind, E. J. ; Spandre, Gloria ; Spinelli, P. ; Suson, D. J. ; Tajima, Hiroyasu ; Thayer, J. B. ; Thompson, David J. ; Torres, Diego F. ; Tosti, Gino ; Troja, Eleonora ; Valverde, J. ; Vianello, Giacomo ; Vogel, M. ; Wood, K. ; Yassine, M. ; Alfaro, R. ; Alvarez, C. ; Alvarez, J. D. ; Arceo, R. ; Arteaga-Velazquez, J. C. ; Rojas, D. Avila ; Ayala Solares, H. A. ; Becerril, A. ; Belmont-Moreno, E. ; BenZvi, S. Y. ; Bernal, A. ; Braun, J. ; Brisbois, C. ; Caballero-Mora, K. S. ; Capistran, T. ; Carraminana, A. ; Casanova, Sabrina ; Castillo, M. ; Cotti, U. ; Cotzomi, J. ; Coutino de Leon, S. ; De Leon, C. ; De la Fuente, E. ; Dichiara, S. ; Dingus, B. L. ; DuVernois, M. A. ; Diaz-Velez, J. C. ; Engel, K. ; Enriquez-Rivera, O. ; Fiorino, D. W. ; Fleischhack, H. ; Fraija, N. ; Garcia-Gonzalez, J. A. ; Garfias, F. ; Gonzalez Munoz, A. ; Gonzalez, M. M. ; Goodman, J. A. ; Hampel-Arias, Z. ; Harding, J. P. ; Hernandez, S. ; Hernandez-Almada, A. ; Hona, B. ; Hueyotl-Zahuantitla, F. ; Hui, C. M. ; Huntemeyer, P. ; Iriarte, A. ; Jardin-Blicq, A. ; Joshi, V. ; Kaufmann, S. ; Lara, A. ; Lauer, R. J. ; Lee, W. H. ; Lennarz, D. ; Leon Vargas, H. ; Linnemann, J. T. ; Longinotti, A. L. ; Luis-Raya, G. ; Luna-Garcia, R. ; Lopez-Coto, R. ; Malone, K. ; Marinelli, S. S. ; Martinez, O. ; Martinez-Castellanos, I. ; Martinez-Castro, J. ; Martinez-Huerta, H. ; Matthews, J. A. ; Miranda-Romagnoli, P. ; Moreno, E. ; Mostafa, M. ; Nayerhoda, A. ; Nellen, L. ; Newbold, M. ; Nisa, M. U. ; Noriega-Papaqui, R. ; Pelayo, R. ; Pretz, J. ; Perez-Perez, E. G. ; Ren, Z. ; Rho, C. D. ; Riviere, C. ; Rosa-Gonzalez, D. ; Rosenberg, M. ; Ruiz-Velasco, E. ; Salazar, H. ; Greus, F. Salesa ; Sandoval, A. ; Schneider, M. ; Arroyo, M. Seglar ; Sinnis, G. ; Smith, A. J. ; Springer, R. W. ; Surajbali, P. ; Taboada, Ignacio ; Tibolla, O. ; Tollefson, K. ; Torres, I. ; Ukwatta, Tilan N. ; Villasenor, L. ; Weisgarber, T. ; Westerhoff, Stefan ; Wisher, I. G. ; Wood, J. ; Yapici, Tolga ; Yodh, G. ; Zepeda, A. ; Zhou, H.
The High Altitude Water Cherenkov (HAWC) collaboration recently published their 2HWC catalog, listing 39 very high energy (VHE; >100 GeV) gamma-ray sources based on 507 days of observation. Among these, 19 sources are not associated with previously known teraelectronvolt (TeV) gamma-ray sources. We have studied 14 of these sources without known counterparts with VERITAS and Fermi-LAT. VERITAS detected weak gamma-ray emission in the 1 TeV-30 TeV band in the region of DA 495, a pulsar wind nebula coinciding with 2HWC J1953+294, confirming the discovery of the source by HAWC. We did not find any counterpart for the selected 14 new HAWC sources from our analysis of Fermi-LAT data for energies higher than 10 GeV. During the search, we detected gigaelectronvolt (GeV) gamma-ray emission coincident with a known TeV pulsar wind nebula, SNR G54.1+0.3 (VER J1930+188), and a 2HWC source, 2HWC J1930+188. The fluxes for isolated, steady sources in the 2HWC catalog are generally in good agreement with those measured by imaging atmospheric Cherenkov telescopes. However, the VERITAS fluxes for SNR G54.1+0.3, DA 495, and TeV J2032+4130 are lower than those measured by HAWC, and several new HAWC sources are not detected by VERITAS. This is likely due to a change in spectral shape, source extension, or the influence of diffuse emission in the source region.
Warrington, Nicole ; Beaumont, Robin ; Horikoshi, Momoko ; Day, Felix R. ; Helgeland, Øyvind ; Laurin, Charles ; Bacelis, Jonas ; Peng, Shouneng ; Hao, Ke ; Feenstra, Bjarke ; Wood, Andrew R. ; Mahajan, Anubha ; Tyrrell, Jessica ; Robertson, Neil R. ; Rayner, N. William ; Qiao, Zhen ; Moen, Gunn-Helen ; Vaudel, Marc ; Marsit, Carmen ; Chen, Jia ; Nodzenski, Michael ; Schnurr, Theresia M. ; Zafarmand, Mohammad Hadi ; Bradfield, Jonathan P. ; Grarup, Niels ; Kooijman, Marjolein N. ; Li-Gao, Ruifang ; Geller, Frank ; Ahluwalia, Tarunveer Singh ; Paternoster, Lavinia ; Rueedi, Rico ; Huikari, Ville ; Hottenga, Jouke-Jan ; Lyytikäinen, Leo-Pekka ; Cavadino, Alana ; Metrustry, Sarah ; Cousminer, Diana L. ; Wu, Ying ; Thiering, Elisabeth Paula ; Wang, Carol A. ; Have, Christian Theil ; Vilor-Tejedor, Natalia ; Joshi, Peter K. ; Painter, Jodie N. ; Ntalla, Ioanna ; Myhre, Ronny ; Pitkänen, Niina ; van Leeuwen, Elisabeth M. ; Joro, Raimo ; Lagou, Vasiliki ; Richmond, Rebecca C. ; Espinosa, Ana ; Barton, Sheila J. ; Inskip, Hazel M. ; Holloway, John W. ; Santa-Marina, Loreto ; Estivill, Xavier ; Ang, Wei ; Marsh, Julie A. ; Reichetzeder, Christoph ; Marullo, Letizia ; Hocher, Berthold ; Lunetta, Kathryn L. ; Murabito, Joanne M. ; Relton, Caroline L. ; Kogevinas, Manolis ; Chatzi, Leda ; Allard, Catherine ; Bouchard, Luigi ; Hivert, Marie-France ; Zhang, Ge ; Muglia, Louis J. ; Heikkinen, Jani ; Morgen, Camilla S. ; van Kampen, Antoine H. C. ; van Schaik, Barbera D. C. ; Mentch, Frank D. ; Langenberg, Claudia ; Scott, Robert A. ; Zhao, Jing Hua ; Hemani, Gibran ; Ring, Susan M. ; Bennett, Amanda J. ; Gaulton, Kyle J. ; Fernandez-Tajes, Juan ; van Zuydam, Natalie R. ; Medina-Gomez, Carolina ; de Haan, Hugoline G. ; Rosendaal, Frits R. ; Kutalik, Zoltán ; Marques-Vidal, Pedro ; Das, Shikta ; Willemsen, Gonneke ; Mbarek, Hamdi ; Müller-Nurasyid, Martina ; Standl, Marie ; Appel, Emil V. R. ; Fonvig, Cilius Esmann ; Trier, Caecilie ; van Beijsterveldt, Catharina E. M. ; Murcia, Mario ; Bustamante, Mariona ; Bonàs-Guarch, Sílvia ; Hougaard, David M. ; Mercader, Josep M. ; Linneberg, Allan ; Schraut, Katharina E. ; Lind, Penelope A. ; Medland, Sarah Elizabeth ; Shields, Beverley M. ; Knight, Bridget A. ; Chai, Jin-Fang ; Panoutsopoulou, Kalliope ; Bartels, Meike ; Sánchez, Friman ; Stokholm, Jakob ; Torrents, David ; Vinding, Rebecca K. ; Willems, Sara M. ; Atalay, Mustafa ; Chawes, Bo L. ; Kovacs, Peter ; Prokopenko, Inga ; Tuke, Marcus A. ; Yaghootkar, Hanieh ; Ruth, Katherine S. ; Jones, Samuel E. ; Loh, Po-Ru ; Murray, Anna ; Weedon, Michael N. ; Tönjes, Anke ; Stumvoll, Michael ; Michaelsen, Kim Fleischer ; Eloranta, Aino-Maija ; Lakka, Timo A. ; van Duijn, Cornelia M. ; Kiess, Wieland ; Koerner, Antje ; Niinikoski, Harri ; Pahkala, Katja ; Raitakari, Olli T. ; Jacobsson, Bo ; Zeggini, Eleftheria ; Dedoussis, George V. ; Teo, Yik-Ying ; Saw, Seang-Mei ; Montgomery, Grant W. ; Campbell, Harry ; Wilson, James F. ; Vrijkotte, Tanja G. M. ; Vrijheid, Martine ; de Geus, Eco J. C. N. ; Hayes, M. Geoffrey ; Kadarmideen, Haja N. ; Holm, Jens-Christian ; Beilin, Lawrence J. ; Pennell, Craig E. ; Heinrich, Joachim ; Adair, Linda S. ; Borja, Judith B. ; Mohlke, Karen L. ; Eriksson, Johan G. ; Widen, Elisabeth E. ; Hattersley, Andrew T. ; Spector, Tim D. ; Kaehoenen, Mika ; Viikari, Jorma S. ; Lehtimaeki, Terho ; Boomsma, Dorret I. ; Sebert, Sylvain ; Vollenweider, Peter ; Sorensen, Thorkild I. A. ; Bisgaard, Hans ; Bonnelykke, Klaus ; Murray, Jeffrey C. ; Melbye, Mads ; Nohr, Ellen A. ; Mook-Kanamori, Dennis O. ; Rivadeneira, Fernando ; Hofman, Albert ; Felix, Janine F. ; Jaddoe, Vincent W. V. ; Hansen, Torben ; Pisinger, Charlotta ; Vaag, Allan A. ; Pedersen, Oluf ; Uitterlinden, Andre G. ; Jarvelin, Marjo-Riitta ; Power, Christine ; Hypponen, Elina ; Scholtens, Denise M. ; Lowe, William L. ; Smith, George Davey ; Timpson, Nicholas J. ; Morris, Andrew P. ; Wareham, Nicholas J. ; Hakonarson, Hakon ; Grant, Struan F. A. ; Frayling, Timothy M. ; Lawlor, Debbie A. ; Njolstad, Pal R. ; Johansson, Stefan ; Ong, Ken K. ; McCarthy, Mark I. ; Perry, John R. B. ; Evans, David M. ; Freathy, Rachel M.
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.
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.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
Middeldorp, Christel M. ; Mahajan, Anubha ; Horikoshi, Momoko ; Robertson, Neil R. ; Beaumont, Robin N. ; Bradfield, Jonathan P. ; Bustamante, Mariona ; Cousminer, Diana L. ; Day, Felix R. ; De Silva, N. Maneka ; Guxens, Monica ; Mook-Kanamori, Dennis O. ; St Pourcain, Beate ; Warrington, Nicole M. ; Adair, Linda S. ; Ahlqvist, Emma ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Ang, Wei ; Atalay, Mustafa ; Auvinen, Juha ; Bartels, Meike ; Beckmann, Jacques S. ; Bilbao, Jose Ramon ; Bond, Tom ; Borja, Judith B. ; Cavadino, Alana ; Charoen, Pimphen ; Chen, Zhanghua ; Coin, Lachlan ; Cooper, Cyrus ; Curtin, John A. ; Custovic, Adnan ; Das, Shikta ; Davies, Gareth E. ; Dedoussis, George V. ; Duijts, Liesbeth ; Eastwood, Peter R. ; Eliasen, Anders U. ; Elliott, Paul ; Eriksson, Johan G. ; Estivill, Xavier ; Fadista, Joao ; Fedko, Iryna O. ; Frayling, Timothy M. ; Gaillard, Romy ; Gauderman, W. James ; Geller, Frank ; Gilliland, Frank ; Gilsanz, Vincente ; Granell, Raquel ; Grarup, Niels ; Groop, Leif ; Hadley, Dexter ; Hakonarson, Hakon ; Hansen, Torben ; Hartman, Catharina A. ; Hattersley, Andrew T. ; Hayes, M. Geoffrey ; Hebebrand, Johannes ; Heinrich, Joachim ; Helgeland, Oyvind ; Henders, Anjali K. ; Henderson, John ; Henriksen, Tine B. ; Hirschhorn, Joel N. ; Hivert, Marie-France ; Hocher, Berthold ; Holloway, John W. ; Holt, Patrick ; Hottenga, Jouke-Jan ; Hypponen, Elina ; Iniguez, Carmen ; Johansson, Stefan ; Jugessur, Astanand ; Kahonen, Mika ; Kalkwarf, Heidi J. ; Kaprio, Jaakko ; Karhunen, Ville ; Kemp, John P. ; Kerkhof, Marjan ; Koppelman, Gerard H. ; Korner, Antje ; Kotecha, Sailesh ; Kreiner-Moller, Eskil ; Kulohoma, Benard ; Kumar, Ashish ; Kutalik, Zoltan ; Lahti, Jari ; Lappe, Joan M. ; Larsson, Henrik ; Lehtimaki, Terho ; Lewin, Alexandra M. ; Li, Jin ; Lichtenstein, Paul ; Lindgren, Cecilia M. ; Lindi, Virpi ; Linneberg, Allan ; Liu, Xueping ; Liu, Jun ; Lowe, William L. ; Lundstrom, Sebastian ; Lyytikainen, Leo-Pekka ; Ma, Ronald C. W. ; Mace, Aurelien ; Magi, Reedik ; Magnus, Per ; Mamun, Abdullah A. ; Mannikko, Minna ; Martin, Nicholas G. ; Mbarek, Hamdi ; McCarthy, Nina S. ; Medland, Sarah E. ; Melbye, Mads ; Melen, Erik ; Mohlke, Karen L. ; Monnereau, Claire ; Morgen, Camilla S. ; Morris, Andrew P. ; Murray, Jeffrey C. ; Myhre, Ronny ; Najman, Jackob M. ; Nivard, Michel G. ; Nohr, Ellen A. ; Nolte, Ilja M. ; Ntalla, Ioanna ; Oberfield, Sharon E. ; Oken, Emily ; Oldehinkel, Albertine J. ; Pahkala, Katja ; Palviainen, Teemu ; Panoutsopoulou, Kalliope ; Pedersen, Oluf ; Pennell, Craig E. ; Pershagen, Goran ; Pitkanen, Niina ; Plomin, Robert ; Power, Christine ; Prasad, Rashmi B. ; Prokopenko, Inga ; Pulkkinen, Lea ; Raikkonen, Katri ; Raitakari, Olli T. ; Reynolds, Rebecca M. ; Richmond, Rebecca C. ; Rivadeneira, Fernando ; Rodriguez, Alina ; Rose, Richard J. ; Salem, Rany ; Santa-Marina, Loreto ; Saw, Seang-Mei ; Schnurr, Theresia M. ; Scott, James G. ; Selzam, Saskia ; Shepherd, John A. ; Simpson, Angela ; Skotte, Line ; Sleiman, Patrick M. A. ; Snieder, Harold ; Sorensen, Thorkild I. A. ; Standl, Marie ; Steegers, Eric A. P. ; Strachan, David P. ; Straker, Leon ; Strandberg, Timo ; Taylor, Michelle ; Teo, Yik-Ying ; Thiering, Elisabeth ; Torrent, Maties ; Tyrrell, Jessica ; Uitterlinden, Andre G. ; van Beijsterveldt, Toos ; van der Most, Peter J. ; van Duijn, Cornelia M. ; Viikari, Jorma ; Vilor-Tejedor, Natalia ; Vogelezang, Suzanne ; Vonk, Judith M. ; Vrijkotte, Tanja G. M. ; Vuoksimaa, Eero ; Wang, Carol A. ; Watkins, William J. ; Wichmann, H-Erich ; Willemsen, Gonneke ; Williams, Gail M. ; Wilson, James F. ; Wray, Naomi R. ; Xu, Shujing ; Xu, Cheng-Jian ; Yaghootkar, Hanieh ; Yi, Lu ; Zafarmand, Mohammad Hadi ; Zeggini, Eleftheria ; Zemel, Babette S. ; Hinney, Anke ; Lakka, Timo A. ; Whitehouse, Andrew J. O. ; Sunyer, Jordi ; Widen, Elisabeth E. ; Feenstra, Bjarke ; Sebert, Sylvain ; Jacobsson, Bo ; Njolstad, Pal R. ; Stoltenberg, Camilla ; Smith, George Davey ; Lawlor, Debbie A. ; Paternoster, Lavinia ; Timpson, Nicholas J. ; Ong, Ken K. ; Bisgaard, Hans ; Bonnelykke, Klaus ; Jaddoe, Vincent W. V. ; Tiemeier, Henning ; Jarvelin, Marjo-Riitta ; Evans, David M. ; Perry, John R. B. ; Grant, Struan F. A. ; Boomsma, Dorret I. ; Freathy, Rachel M. ; McCarthy, Mark I. ; Felix, Janine F.
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Archambault, S. ; Arlen, T. ; Aune, T. ; Beilicke, M. ; Benbow, W. ; Bird, R. ; Boettcher, Markus ; Bouvier, A. ; Buckley, J. H. ; Bugaev, V. ; Ciupik, L. ; Collins-Hughes, E. ; Connolly, M. P. ; Cui, W. ; Dickherber, R. ; Dumm, J. ; Errando, M. ; Falcone, A. ; Federici, Simone ; Feng, Q. ; Finley, J. P. ; Fortson, L. ; Furniss, A. ; Galante, N. ; Gall, D. ; Garson, A. III. ; Gillanders, G. H. ; Griffin, S. ; Grube, J. ; Gusbar, C. ; Gyuk, G. ; Hanna, D. ; Holder, J. ; Hughes, G. ; Kaaret, P. ; Kertzman, M. ; Khassen, Y. ; Kieda, D. ; Krawczynski, H. ; Lamerato, A. ; Lang, M. J. ; Li, K. ; Madhavan, A. S. ; Maier, G. ; Majumdar, P. ; McArthur, S. ; McCann, A. ; Millis, J. ; Moriarty, P. ; Mukherjee, R. ; Nieto, D. ; Ong, R. A. ; Orr, M. ; Otte, A. N. ; Park, N. ; Perkins, J. S. ; Pohl, Martin ; Popkow, A. ; Prokoph, H. ; Quinn, J. ; Ragan, K. ; Reynolds, P. T. ; Richards, G. T. ; Roache, E. ; Roustazadeh, P. ; Saxon, D. B. ; Sembroski, G. H. ; Senturk, G. D. ; Skole, C. ; Staszak, D. ; Telezhinsky, Igor O. ; Tesic, G. ; Theiling, M. ; Varlotta, A. ; Vassiliev, V. V. ; Vincent, S. ; Wakely, S. P. ; Weinstein, A. ; Welsing, R. ; Williams, D. A. ; Zitzer, B.
We present the results of a multi-wavelength campaign targeting the blazar 1ES 1218+30.4 with observations with the 1.3 m McGraw-Hill optical telescope, the Rossi X-ray Timing Explorer (RXTE), the Fermi Gamma-Ray Space Telescope, and the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The RXTE and VERITAS observations were spread over a 13 day period and revealed clear evidence for flux variability, and a strong X-ray and gamma-ray flare on 2009 February 26 (MJD 54888). The campaign delivered a well-sampled broadband energy spectrum with simultaneous RXTE and VERITAS very high energy (VHE, > 100 GeV) observations, as well as contemporaneous optical and Fermi observations. The 1ES 1218+30.4 broadband energy spectrum-the first with simultaneous X-ray and VHE gamma-ray energy spectra-is of particular interest as the source is located at a high cosmological redshift for a VHE source (z = 0.182), leading to strong absorption of VHE gamma rays by photons from the optical/infrared extragalactic background light (EBL) via gamma VHE +gamma EBL -> e(+) e(-)pair-creation processes. We model the data with a one-zone synchrotron self-Compton (SSC) emission model and with the extragalactic absorption predicted by several recent EBL models. We find that the observations are consistent with the SSC scenario and all the EBL models considered in this work. We discuss observational and theoretical avenues to improve on the EBL constraints.
Van Hout, Cristopher V. ; Tachmazidou, Ioanna ; Backman, Joshua D. ; Hoffman, Joshua D. ; Liu, Daren ; Pandey, Ashutosh K. ; Gonzaga-Jauregui, Claudia ; Khalid, Shareef ; Ye, Bin ; Banerjee, Nilanjana ; Li, Alexander H. ; O'Dushlaine, Colm ; Marcketta, Anthony ; Staples, Jeffrey ; Schurmann, Claudia ; Hawes, Alicia ; Maxwell, Evan ; Barnard, Leland ; Lopez, Alexander ; Penn, John ; Habegger, Lukas ; Blumenfeld, Andrew L. ; Bai, Xiaodong ; O'Keeffe, Sean ; Yadav, Ashish ; Praveen, Kavita ; Jones, Marcus ; Salerno, William J. ; Chung, Wendy K. ; Surakka, Ida ; Willer, Cristen J. ; Hveem, Kristian ; Leader, Joseph B. ; Carey, David J. ; Ledbetter, David H. ; Cardon, Lon ; Yancopoulos, George D. ; Economides, Aris ; Coppola, Giovanni ; Shuldiner, Alan R. ; Balasubramanian, Suganthi ; Cantor, Michael ; Nelson, Matthew R. ; Whittaker, John ; Reid, Jeffrey G. ; Marchini, Jonathan ; Overton, John D. ; Scott, Robert A. ; Abecasis, Goncalo R. ; Yerges-Armstrong, Laura M. ; Baras, Aris
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. <br /> Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction
(2019)
Wolf, Thomas J. A. ; Sanchez, David M. ; Yang, J. ; Parrish, R. M. ; Nunes, J. P. F. ; Centurion, M. ; Coffee, R. ; Cryan, J. P. ; Gühr, Markus ; Hegazy, Kareem ; Kirrander, Adam ; Li, R. K. ; Ruddock, J. ; Shen, Xiaozhe ; Vecchione, T. ; Weathersby, S. P. ; Weber, Peter M. ; Wilkin, K. ; Yong, Haiwang ; Zheng, Q. ; Wang, X. J. ; Minitti, Michael P. ; Martinez, Todd J.
The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subangstrom length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
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.
The selaginella genome identifies genetic changes associated with the evolution of vascular plants
(2011)
Banks, Jo Ann ; Nishiyama, Tomoaki ; Hasebe, Mitsuyasu ; Bowman, John L. ; Gribskov, Michael ; dePamphilis, Claude ; Albert, Victor A. ; Aono, Naoki ; Aoyama, Tsuyoshi ; Ambrose, Barbara A. ; Ashton, Neil W. ; Axtell, Michael J. ; Barker, Elizabeth ; Barker, Michael S. ; Bennetzen, Jeffrey L. ; Bonawitz, Nicholas D. ; Chapple, Clint ; Cheng, Chaoyang ; Correa, Luiz Gustavo Guedes ; Dacre, Michael ; DeBarry, Jeremy ; Dreyer, Ingo ; Elias, Marek ; Engstrom, Eric M. ; Estelle, Mark ; Feng, Liang ; Finet, Cedric ; Floyd, Sandra K. ; Frommer, Wolf B. ; Fujita, Tomomichi ; Gramzow, Lydia ; Gutensohn, Michael ; Harholt, Jesper ; Hattori, Mitsuru ; Heyl, Alexander ; Hirai, Tadayoshi ; Hiwatashi, Yuji ; Ishikawa, Masaki ; Iwata, Mineko ; Karol, Kenneth G. ; Koehler, Barbara ; Kolukisaoglu, Uener ; Kubo, Minoru ; Kurata, Tetsuya ; Lalonde, Sylvie ; Li, Kejie ; Li, Ying ; Litt, Amy ; Lyons, Eric ; Manning, Gerard ; Maruyama, Takeshi ; Michael, Todd P. ; Mikami, Koji ; Miyazaki, Saori ; Morinaga, Shin-ichi ; Murata, Takashi ; Müller-Röber, Bernd ; Nelson, David R. ; Obara, Mari ; Oguri, Yasuko ; Olmstead, Richard G. ; Onodera, Naoko ; Petersen, Bent Larsen ; Pils, Birgit ; Prigge, Michael ; Rensing, Stefan A. ; Mauricio Riano-Pachon, Diego ; Roberts, Alison W. ; Sato, Yoshikatsu ; Scheller, Henrik Vibe ; Schulz, Burkhard ; Schulz, Christian ; Shakirov, Eugene V. ; Shibagaki, Nakako ; Shinohara, Naoki ; Shippen, Dorothy E. ; Sorensen, Iben ; Sotooka, Ryo ; Sugimoto, Nagisa ; Sugita, Mamoru ; Sumikawa, Naomi ; Tanurdzic, Milos ; Theissen, Guenter ; Ulvskov, Peter ; Wakazuki, Sachiko ; Weng, Jing-Ke ; Willats, William W. G. T. ; Wipf, Daniel ; Wolf, Paul G. ; Yang, Lixing ; Zimmer, Andreas D. ; Zhu, Qihui ; Mitros, Therese ; Hellsten, Uffe ; Loque, Dominique ; Otillar, Robert ; Salamov, Asaf ; Schmutz, Jeremy ; Shapiro, Harris ; Lindquist, Erika ; Lucas, Susan ; Rokhsar, Daniel ; Grigoriev, Igor V.
Vascular plants appeared similar to 410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
Aldoretta, E. J. ; St-Louis, N. ; Richardson, N. D. ; Moffat, Anthony F. J. ; Eversberg, T. ; Hill, G. M. ; Shenar, Tomer ; Artigau, E. ; Gauza, B. ; Knapen, J. H. ; Kubat, Jiří ; Kubatova, Brankica ; Maltais-Tariant, R. ; Munoz, M. ; Pablo, H. ; Ramiaramanantsoa, T. ; Richard-Laferriere, A. ; Sablowski, D. P. ; Simon-Diaz, S. ; St-Jean, L. ; Bolduan, F. ; Dias, F. M. ; Dubreuil, P. ; Fuchs, D. ; Garrel, T. ; Grutzeck, G. ; Hunger, T. ; Kuesters, D. ; Langenbrink, M. ; Leadbeater, R. ; Li, D. ; Lopez, A. ; Mauclaire, B. ; Moldenhawer, T. ; Potter, M. ; dos Santos, E. M. ; Schanne, L. ; Schmidt, J. ; Sieske, H. ; Strachan, J. ; Stinner, E. ; Stinner, P. ; Stober, B. ; Strandbaek, K. ; Syder, T. ; Verilhac, D. ; Waldschlaeger, U. ; Weiss, D. ; Wendt, A.
During the summer of 2013, a 4-month spectroscopic campaign took place to observe the variabilities in three Wolf-Rayet stars. The spectroscopic data have been analysed for WR 134 (WN6b), to better understand its behaviour and long-term periodicity, which we interpret as arising from corotating interaction regions (CIRs) in the wind. By analysing the variability of the He ii lambda 5411 emission line, the previously identified period was refined to P = 2.255 +/- 0.008 (s.d.) d. The coherency time of the variability, which we associate with the lifetime of the CIRs in the wind, was deduced to be 40 +/- 6 d, or similar to 18 cycles, by cross-correlating the variability patterns as a function of time. When comparing the phased observational grey-scale difference images with theoretical grey-scales previously calculated from models including CIRs in an optically thin stellar wind, we find that two CIRs were likely present. A separation in longitude of Delta I center dot a parts per thousand integral 90A degrees was determined between the two CIRs and we suggest that the different maximum velocities that they reach indicate that they emerge from different latitudes. We have also been able to detect observational signatures of the CIRs in other spectral lines (C iv lambda lambda 5802,5812 and He i lambda 5876). Furthermore, a DAC was found to be present simultaneously with the CIR signatures detected in the He i lambda 5876 emission line which is consistent with the proposed geometry of the large-scale structures in the wind. Small-scale structures also show a presence in the wind, simultaneously with the larger scale structures, showing that they do in fact co-exist.
Cook, Katherine V. ; Li, Chuang ; Cai, Haiyuan ; Krumholz, Lee R. ; Hambright, K. David ; Paerl, Hans W. ; Steffen, Morgan M. ; Wilson, Alan E. ; Burford, Michele A. ; Grossart, Hans-Peter ; Hamilton, David P. ; Jiang, Helong ; Sukenik, Assaf ; Latour, Delphine ; Meyer, Elisabeth I. ; Padisak, Judit ; Qin, Boqiang ; Zamor, Richard M. ; Zhu, Guangwei
Bacteria play key roles in the function and diversity of aquatic systems, but aside from study of specific bloom systems, little is known about the diversity or biogeography of bacteria associated with harmful cyanobacterial blooms (cyanoHABs). CyanoHAB species are known to shape bacterial community composition and to rely on functions provided by the associated bacteria, leading to the hypothesized cyanoHAB interactome, a coevolved community of synergistic and interacting bacteria species, each necessary for the success of the others. Here, we surveyed the microbiome associated with Microcystis aeruginosa during blooms in 12 lakes spanning four continents as an initial test of the hypothesized Microcystis interactome. We predicted that microbiome composition and functional potential would be similar across blooms globally. Our results, as revealed by 16S rRNA sequence similarity, indicate that M. aeruginosa is cosmopolitan in lakes across a 280 degrees longitudinal and 90 degrees latitudinal gradient. The microbiome communities were represented by a wide range of operational taxonomic units and relative abundances. Highly abundant taxa were more related and shared across most sites and did not vary with geographic distance, thus, like Microcystis, revealing no evidence for dispersal limitation. High phylogenetic relatedness, both within and across lakes, indicates that microbiome bacteria with similar functional potential were associated with all blooms. While Microcystis and the microbiome bacteria shared many genes, whole-community metagenomic analysis revealed a suite of biochemical pathways that could be considered complementary. Our results demonstrate a high degree of similarity across global Microcystis blooms, thereby providing initial support for the hypothesized Microcystis interactome.
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