@article{VanHoutTachmazidouBackmanetal.2020, author = {Van Hout, Cristopher V. and Tachmazidou, Ioanna and Backman, Joshua D. and Hoffman, Joshua D. and Liu, Daren and Pandey, Ashutosh K. and Gonzaga-Jauregui, Claudia and Khalid, Shareef and Ye, Bin and Banerjee, Nilanjana and Li, Alexander H. and O'Dushlaine, Colm and Marcketta, Anthony and Staples, Jeffrey and Schurmann, Claudia and Hawes, Alicia and Maxwell, Evan and Barnard, Leland and Lopez, Alexander and Penn, John and Habegger, Lukas and Blumenfeld, Andrew L. and Bai, Xiaodong and O'Keeffe, Sean and Yadav, Ashish and Praveen, Kavita and Jones, Marcus and Salerno, William J. and Chung, Wendy K. and Surakka, Ida and Willer, Cristen J. and Hveem, Kristian and Leader, Joseph B. and Carey, David J. and Ledbetter, David H. and Cardon, Lon and Yancopoulos, George D. and Economides, Aris and Coppola, Giovanni and Shuldiner, Alan R. and Balasubramanian, Suganthi and Cantor, Michael and Nelson, Matthew R. and Whittaker, John and Reid, Jeffrey G. and Marchini, Jonathan and Overton, John D. and Scott, Robert A. and Abecasis, Goncalo R. and Yerges-Armstrong, Laura M. and Baras, Aris}, title = {Exome sequencing and characterization of 49,960 individuals in the UK Biobank}, series = {Nature : the international weekly journal of science}, volume = {586}, journal = {Nature : the international weekly journal of science}, number = {7831}, publisher = {Macmillan Publishers Limited}, address = {London}, organization = {Regeneron Genetics Ctr}, issn = {0028-0836}, doi = {10.1038/s41586-020-2853-0}, pages = {749 -- 756}, year = {2020}, abstract = {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.
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.}, language = {en} } @article{MantzoukiCampbellvanLoonetal.2018, author = {Mantzouki, Evanthia and Campbell, James and van Loon, Emiel and Visser, Petra and Konstantinou, Iosif and Antoniou, Maria and Giuliani, Gregory and Machado-Vieira, Danielle and de Oliveira, Alinne Gurjao and Maronic, Dubravka Spoljaric and Stevic, Filip and Pfeiffer, Tanja Zuna and Vucelic, Itana Bokan and Zutinic, Petar and Udovic, Marija Gligora and Plenkovic-Moraj, Andelka and Tsiarta, Nikoletta and Blaha, Ludek and Geris, Rodan and Frankova, Marketa and Christoffersen, Kirsten Seestern and Warming, Trine Perlt and Feldmann, Tonu and Laas, Alo and Panksep, Kristel and Tuvikene, Lea and Kangro, Kersti and Haggqvist, Kerstin and Salmi, Pauliina and Arvola, Lauri and Fastner, Jutta and Straile, Dietmar and Rothhaupt, Karl-Otto and Fonvielle, Jeremy Andre and Grossart, Hans-Peter and Avagianos, Christos and Kaloudis, Triantafyllos and Triantis, Theodoros and Zervou, Sevasti-Kiriaki and Hiskia, Anastasia and Gkelis, Spyros and Panou, Manthos and McCarthy, Valerie and Perello, Victor C. and Obertegger, Ulrike and Boscaini, Adriano and Flaim, Giovanna and Salmaso, Nico and Cerasino, Leonardo and Koreiviene, Judita and Karosiene, Jurate and Kasperoviciene, Jurate and Savadova, Ksenija and Vitonyte, Irma and Haande, Sigrid and Skjelbred, Birger and Grabowska, Magdalena and Karpowicz, Maciej and Chmura, Damian and Nawrocka, Lidia and Kobos, Justyna and Mazur-Marzec, Hanna and Alcaraz-Parraga, Pablo and Wilk-Wozniak, Elzbieta and Krzton, Wojciech and Walusiak, Edward and Gagala, Ilona and Mankiewicz-Boczek, Joana and Toporowska, Magdalena and Pawlik-Skowronska, Barbara and Niedzwiecki, Michal and Peczula, Wojciech and Napiorkowska-Krzebietke, Agnieszka and Dunalska, Julita and Sienska, Justyna and Szymanski, Daniel and Kruk, Marek and Budzynska, Agnieszka and Goldyn, Ryszard and Kozak, Anna and Rosinska, Joanna and Szelag-Wasielewska, Elzbieta and Domek, Piotr and Jakubowska-Krepska, Natalia and Kwasizur, Kinga and Messyasz, Beata and Pelechata, Aleksandra and Pelechaty, Mariusz and Kokocinski, Mikolaj and Madrecka, Beata and Kostrzewska-Szlakowska, Iwona and Frak, Magdalena and Bankowska-Sobczak, Agnieszka and Wasilewicz, Michal and Ochocka, Agnieszka and Pasztaleniec, Agnieszka and Jasser, Iwona and Antao-Geraldes, Ana M. and Leira, Manel and Hernandez, Armand and Vasconcelos, Vitor and Morais, Joao and Vale, Micaela and Raposeiro, Pedro M. and Goncalves, Vitor and Aleksovski, Boris and Krstic, Svetislav and Nemova, Hana and Drastichova, Iveta and Chomova, Lucia and Remec-Rekar, Spela and Elersek, Tina and Delgado-Martin, Jordi and Garcia, David and Luis Cereijo, Jose and Goma, Joan and Carmen Trapote, Mari and Vegas-Vilarrubia, Teresa and Obrador, Biel and Garcia-Murcia, Ana and Real, Monserrat and Romans, Elvira and Noguero-Ribes, Jordi and Parreno Duque, David and Fernandez-Moran, Elisabeth and Ubeda, Barbara and Angel Galvez, Jose and Marce, Rafael and Catalan, Nuria and Perez-Martinez, Carmen and Ramos-Rodriguez, Eloisa and Cillero-Castro, Carmen and Moreno-Ostos, Enrique and Maria Blanco, Jose and Rodriguez, Valeriano and Juan Montes-Perez, Jorge and Palomino, Roberto L. and Rodriguez-Perez, Estela and Carballeira, Rafael and Camacho, Antonio and Picazo, Antonio and Rochera, Carlos and Santamans, Anna C. and Ferriol, Carmen and Romo, Susana and Soria, Juan Miguel and Hansson, Lars-Anders and Urrutia-Cordero, Pablo and Ozen, Arda and Bravo, Andrea G. and Buck, Moritz and Colom-Montero, William and Mustonen, Kristiina and Pierson, Don and Yang, Yang and Verspagen, Jolanda M. H. and Domis, Lisette N. de Senerpont and Seelen, Laura and Teurlincx, Sven and Verstijnen, Yvon and Lurling, Miquel and Maliaka, Valentini and Faassen, Elisabeth J. and Latour, Delphine and Carey, Cayelan C. and Paerl, Hans W. and Torokne, Andrea and Karan, Tunay and Demir, Nilsun and Beklioglu, Meryem and Filiz, Nur and Levi, Eti E. and Iskin, Ugur and Bezirci, Gizem and Tavsanoglu, Ulku Nihan and Celik, Kemal and Ozhan, Koray and Karakaya, Nusret and Kocer, Mehmet Ali Turan and Yilmaz, Mete and Maraslioglu, Faruk and Fakioglu, Ozden and Soylu, Elif Neyran and Yagci, Meral Apaydin and Cinar, Sakir and Capkin, Kadir and Yagci, Abdulkadir and Cesur, Mehmet and Bilgin, Fuat and Bulut, Cafer and Uysal, Rahmi and Koker, Latife and Akcaalan, Reyhan and Albay, Meric and Alp, Mehmet Tahir and Ozkan, Korhan and Sevindik, Tugba Ongun and Tunca, Hatice and Onem, Burcin and Richardson, Jessica and Edwards, Christine and Bergkemper, Victoria and Beirne, Eilish and Cromie, Hannah and Ibelings, Bastiaan W.}, title = {Data Descriptor: A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins}, series = {Scientific Data}, volume = {5}, journal = {Scientific Data}, publisher = {Nature Publ. Group}, address = {London}, issn = {2052-4463}, doi = {10.1038/sdata.2018.226}, pages = {13}, year = {2018}, abstract = {Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.}, language = {en} }