11 research outputs found
Planning Car Painting Workshop for Tuuliku Reisid OÜ
No full textLõputöö eesmärgiks on luua ettevõtte Tuuliku Reisid OÜ remonditöökoja kõrvale värvitööde osakond, kus pakutakse kvaliteetseid teenuseid. Lõputöö kirjutamist alustati ettevõtte Tuuliku reisid OÜ tutvustusega, kus anti ülevaade ettevõtte asukohast ja hoonest ning kirjeldati ettevõttes pakutavaid teenuseid ja ettevõtte struktuuri. Samuti tutvustati teoreetilises osas autode remontvärvimist ja selle protsessi. Antud lõputöö käigus koostas autor ettevõtte Tuuliku Reisid OÜ jaoks planeeritava värvitöökoja skeemi koos seadmete eeldatava paigutusega. Samuti koostas autor ettevõttele planeeritavas värvitöökojas vajamineva inventari ja tööriistade loetelu koos maksumusega. Lõputöö käigus selgus, et konkurents Kagu-Eestis pole suur, kuid kindlasti hakkavad planeeritavat värvitöökoda mõjutama Tartu linnas asuvad värvitöökojad. Värvimisteenuste pakkujate otsimise käigus, selgus, et selliseid ametlikult registreeritud ettevõtteid on väga vähe, kes pakuvad usaldusväärset teenust ning, mistõttu on värvitöökoja rajamine Tuuliku Reisid OÜ-sse autori arvates otstarbekas. Lõputöö käigus prognoositi ka planeeritava värvitöökoja tasuvust. Lõputöö autor jõudis käesoleva töö käigus järeldusele, et toimiva ja eduka värvitöökoja loomiseks on vaja analüüsida oma äriideed, mis võimaldab likvideerida kitsaskohad enne teenuse osutamise alustamist ja hoida kokku rahalisi ressursse. Lõputöö tulemusena valmis autori poolt koostatud töökoja kavand ja tasuvusarvutused, mida ettevõte saab kasutada värvitöökoja projekteerimiseks ja äriplaani kirjutamisel.The aim of the dissertation is to create a paint work department next to the repair shop of the company Tuuliku Reisid OÜ, where high-quality services are offered. The writing of the dissertation started with the introduction of the company Tuuliku reisid OÜ, where an overview of the company's location and building was given. Also, services offered by the company and leadership of the company's structure were described. The theoretical part of the paper introduced car repair painting and its process. During this dissertation, the author prepared the scheme of the paint shop planned for the company Tuuliku Reisid OÜ together with the expected layout of the equipment. The author also made a list of the equipment and tools needed for the paint shop with the cost. It became clear that the competition in South-Eastern Estonia is not great, but the paint shops what are located in Tartu will definitely start to influence the planned paint shop. During the dissertation, the profitability of the planned paint shop was also predicted. In the course of this work the author became to the conclusion that in order to create a functioning and successful paint shop, it is necessary to analyse your business idea, which allows eliminating bottlenecks before starting the service and saving financial resources. As a result of the dissertation, the workshop plan and profitability calculations prepared by the author were completed, which the company can use to design a paint shop and write a business plan
Cohort Profiles: Personality Measurements at the Estonian Biobank of the Estonian Genome Center, University of Tartu
No full textLike all behaviour, personality traits are substantially heritable, but their genetic background is poorly understood. Investigating traits’ genetic background could help explain disparities in health and other life outcomes they contribute to. We describe two cohorts of the Estonian Biobank for whom, besides self- and informant-rated personality traits, detailed data are available on a wide range of measures including health behaviour, biomarkers, anthropometric measurements, and medical diagnoses and treatments. The first cohort (N_self-report = 3,640, N_informant-report = 3,488) filled out the NEO Personality Inventory-3 (NEO-PI-3) between 2008 and 2018. The second cohort (N_self-report = 77,400, N_informant-report = 21,986), collected between 2021 and 2022, responded to a large and diverse item pool called the 100 Nuances of Personality (100NP) covering the Big Five and other traits. Research opportunities include investigation of personality traits’ properties, gene discovery, prediction of health and well-being, and causal modelling. New data are added periodically through additional data collection waves and linkage with various registries and databases
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
No full textVariability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types. © 2021 The Author(s
Mapping the human genetic architecture of COVID-19
No full textnone3597The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.noneNiemi, Mari E. K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark; Ganna, Andrea; Pathak, Gita A.; Andrews, Shea J.; Kanai, Masahiro; Veerapen, Kumar; Fernandez-Cadenas, Israel; Schulte, Eva C.; Striano, Pasquale; Marttila, Minttu; Minica, Camelia; Marouli, Eirini; Karim, Mohd Anisul; Wendt, Frank R.; Savage, Jeanne; Sloofman, Laura; Butler-Laporte, Guillaume; Kim, Han-Na; Kanoni, Stavroula; Okada, Yukinori; Byun, Jinyoung; Han, Younghun; Uddin, Mohammed Jashim; Smith, George Davey; Willer, Cristen J.; Buxbaum, Joseph D.; Mehtonen, Juha; Finucane, Hilary; Cordioli, Mattia; Martin, Alicia R.; Zhou, Wei; Pasaniuc, Bogdan; Julienne, Hanna; Aschard, Hugues; Shi, Huwenbo; Yengo, Loic; Polimanti, Renato; Ghoussaini, Maya; Schwartzentruber, Jeremy; Dunham, Ian; Chwialkowska, Karolina; Francescatto, Margherita; Trankiem, Amy; Balaconis, Mary K.; Davis, Lea; Lee, Sulggi; Priest, James; Renieri, Alessandra; Sankaran, Vijay G.; van Heel, David; Deelen, Patrick; Richards, J. Brent; Nakanishi, Tomoko; Biesecker, Les; Kerchberger, V. Eric; Baillie, J. Kenneth; Mari, Francesca; Bernasconi, Anna; Baillie, Stefano Ceri; Canakoglu, Arif; Wolford, Brooke; Faucon, Annika; Dutta, Atanu Kumar; Schurmann, Claudia; Harry, Emi; Birney, Ewan; Nguyen, Huy; Nasir, Jamal; Kaunisto, Mari; Solomonson, Matthew; Dueker, Nicole; Vadgama, Nirmal; Limou, Sophie; Rahmouni, Souad; Mbarek, Hamdi; Darwish, Dima; Uddin, Md Mesbah; Albertos, Raquel; Pérez-Tur, Jordi; Li, Ruolin; Folkersen, Lasse; Moltke, Ida; Koelling, Nils; Teumer, Alexander; Kousathanas, Athanasios; Utrilla, Alicia; Verdugo, Ricardo A.; Zárate, Ruth; Medina-Gómez, Carolina; Gómez-Cabrero, David; Carnero-Montoro, Elena; Cadilla, Carmen L.; Moreno-Estrada, Andrés; Garmendia, Adriana; Moya, Leire; Sedaghati-Khayat, Bahar; Boua, Palwendé Romuald; Favé, Marie-Julie; Francioli, Laurent; Lemaçon, Audrey; Migeotte, Isabelle; Patel, Sanjay; Varnai, Reka; Szentpeteri, Jozsef L.; Sipeky, Csilla; Colombo, Francesca; von Hohenstaufen, Kathrin; Lio, Pietro; Vallerga, Costanza; Wang, Qingbo; Tanigawa, Yosuke; Im, Hogune; Han, Chulho; Song, Han; Lim, Jiwoo; Lee, Younhe; Kim, Sugyeong; Im, Sangyoon; Atanasovska, Biljana; Ahmad, Hajar Fauzan; Boer, Cindy; Jansen, Philip; Franke, Lude; Kaja, Elżbieta; Pasko, Dorota; Kennis-Szilagyi, Ingrid; Kornilov, Sergey A.; Prijatelj, Vid; Prokić, Ivana; Sivanadhan, Ilangkumaran; Perumal, Sarala; Esmaeeli, Sahar; Pearson, Nathaniel M.; Auton, Adam; Shelton, Janie F.; Shastri, Anjali J.; Filshtein-Sonmez, Teresa; Coker, Daniella; Symons, Antony; Esparza-Gordillo, Jorge; Aslibekyan, Stella; O’Connell, Jared; Ye, Chelsea; Weldon, Catherine H.; Perera, Minoli; O’Leary, Kevin; Tuck, Matthew; O’Brien, Travis; Meltzer, David; O’Donnell, Peter; Nutescu, Edith; Yang, Guang; Alarcon, Cristina; Herrmann, Stefanie; Mazurek, Sophia; Banagan, Jeff; Hamidi, Zacharia; Barbour, April; Raffat, Noora; Moreno, Diana; Friedman, Paula; Ferwerda, Bart; van de Beek, Diederik; Brouwer, Matthijs C.; Vlaar, Alexander P. J.; Wiersinga, W. Joost; Posthuma, Danielle; Tissink, Elleke; Koos Zwinderman, A. H.; Uffelmann, Emil; van Agtmael, Michiel; Algera, Anne Geke; van Baarle, Frank; Bax, Diane; Beudel, Martijn; Jan Bogaard, Harm; Bomers, Marije; Bonta, Peter I.; Bos, Lieuwe; Botta, Michela; de Brabander, Justin; de Bree, Godelieve; de Bruin, Sanne; Bugiani, Marianna; Bulle, Esther; Chouchane, Osoul; Cloherty, Alex; Dongelmans, Dave; Elbers, Paul; Fleuren, Lucas; Geerlings, Suzanne; Geerts, Bart; Geijtenbeek, Theo; Girbes, Armand; Goorhuis, Bram; Grobusch, Martin P.; Hafkamp, Florianne; Hagens, Laura; Hamann, Jorg; Harris, Vanessa; Hemke, Robert; Hermans, Sabine M.; Heunks, Leo; Hollmann, Markus; Horn, Janneke; Hovius, Joppe W.; de Jong, Menno D.; Koning, Rutger; van Mourik, Niels; Nellen, Jeannine; Nossent, Esther J.; Paulus, Frederique; Peters, Edgar; van der Poll, Tom; Preckel, Bennedikt; Prins, Jan M.; Raasveld, Jorinde; Reijnders, Tom; Schinkel, Michiel; Schultz, Marcus J.; Schuurman, Alex; Sigaloff, Kim; Smit, Marry; Stijnis, Cornelis S.; Stilma, Willemke; Teunissen, Charlotte; Thoral, Patrick; Tsonas, Anissa; van der Valk, Marc; Veelo, Denise; de Vries, Heder; van Vugt, Michèle; Wouters, Dorien; Minnaar, René P.; Kromhout, Adrie; van Uffelen, Kees W. J.; Wolterman, Ruud A.; Roberts, Genevieve; Park, Danny; Ball, Catherine A.; Coignet, Marie; McCurdy, Shannon; Knight, Spencer; Partha, Raghavendran; Rhead, Brooke; Zhang, Miao; Berkowitz, Nathan; Gaddis, Michael; Noto, Keith; Ruiz, Luong; Pavlovic, Milos; Hong, Eurie L.; Rand, Kristin; Girshick, Ahna; Guturu, Harendra; Baltzell, Asher Haug; Rahmouni, Souad; Guntz, Julien; Beguin, Yves; Pigazzini, Sara; Nkambule, Lindokuhle; Bouysran, Youssef; Busson, Adeline; Peyrassol, Xavier; Wilkin, Françoise; Pichon, Bruno; Smits, Guillaume; Vandernoot, Isabelle; Goffard, Jean-Christophe; Georges, Michel; Moutschen, Michel; Misset, Benoit; Darcis, Gilles; Guiot, Julien; Jadot, Laurent; Azarzar, Samira; Dellot, Patricia; Gofflot, Stéphanie; Claassen, Sabine; Bertrand, Axelle; Parzibut, Gilles; Clarinval, Mathilde; Moermans, Catherine; Malaise, Olivier; El Kandoussi, Kamilia; Thonon, Raphaël; Huynen, Pascale; Mesdagh, Alyssia; Melo, Sofia; Jacques, Nicolas; Di Valentin, Emmanuel; Giroule, François; Collignon, Alice; Radermecker, Coraline; Lebrun, Marielle; Perée, Hélène; Latour, Samuel; Barada, Olivia; Sanchez, Judit; Josse, Claire; Boujemla, Bouchra; Meunier, Margot; Mariavelle, Emeline; Anania, Sandy; Gazon, Hélène; Juszczak, Danusia; Fadeur, Marjorie; Camby, Séverine; Meuris, Christelle; Thys, Marie; Jacques, Jessica; Henket, Monique; Léonard, Philippe; Frippiat, Frederic; Giot, Jean-Baptiste; Sauvage, Anne-Sophie; Von Frenckell, Christian; Mni, Myriam; Wéry, Marie; Staderoli, Alicia; Belhaj, Yasmine; Lambermont, Bernard; Morrison, David R.; Mooser, Vincent; Forgetta, Vincenzo; Li, Rui; Ghosh, Biswarup; Laurent, Laetitia; Belisle, Alexandre; Henry, Danielle; Abdullah, Tala; Adeleye, Olumide; Mamlouk, Noor; Kimchi, Nofar; Afrasiabi, Zaman; Rezk, Nardin; Vulesevic, Branka; Bouab, Meriem; Guzman, Charlotte; Petitjean, Louis; Tselios, Chris; Xue, Xiaoqing; Afilalo, Jonathan; Afilalo, Marc; Oliveira, Maureen; Brenner, Bluma; Brassard, Nathalie; Durand, Madeleine; Schurr, Erwin; Lepage, Pierre; Ragoussis, Jiannis; Auld, Daniel; Chassé, Michaël; Kaufmann, Daniel E.; Lathrop, G. Mark; Adra, Darin; Davis, Lea K.; Cox, Nancy J.; Below, Jennifer E.; Sealock, Julia M.; Faucon, Annika B.; Shuey, Megan M.; Polikowsky, Hannah G.; Petty, Lauren E.; Shaw, Douglas M.; Chen, Hung-Hsin; Zhu, Wanying; Ludwig, Kerstin U.; Schröder, Julia; Maj, Carlo; Rolker, Selina; Nöthen, Markus M.; Fazaal, Julia; Keitel, Verena; Jensen, Björn-Erik Ole; Feldt, Torsten; Kurth, Ingo; Marx, Nikolaus; Dreher, Michael; Pink, Isabell; Cornberg, Markus; Illig, Thomas; Lehmann, Clara; Schommers, Philipp; Augustin, Max; Rybniker, Jan; Knopp, Lisa; Eggermann, Thomas; Volland, Sonja; Altmüller, Janine; Berger, Marc M.; Brenner, Thorsten; Hinney, Anke; Witzke, Oliver; Bals, Robert; Herr, Christian; Ludwig, Nicole; Walter, Jörn; Fuchsberger, Christian; Pattaro, Cristian; De Grandi, Alessandro; Pramstaller, Peter; Emmert, David; Melotti, Roberto; Foco, Luisa; Mascalzoni, Deborah; Gögele, Martin; Domingues, Francisco; Hicks, Andrew; Gignoux, Christopher R.; Wicks, Stephen J.; Crooks, Kristy; Barnes, Kathleen C.; Daya, Michelle; Shortt, Jonathan; Rafaels, Nicholas; Chavan, Sameer; Goldstein, David B.; Kiryluk, Krzysztof; Sengupta, Soumitra; Chung, Wendy; Reilly, Muredach P.; Khan, Atlas; Wang, Chen; Povysil, Gundula; Bhardwaj, Nitin; Gharavi, Ali G.; Ionita-Laza, Iuliana; Shang, Ning; O’Byrne, Sheila M.; Nandakumar, Renu; Menon, Amritha; So, Yat S.; Hod, Eldad; Pendrick, Danielle; Kim, Han-Na; Park, Soo-Kyung; Kim, Hyung-Lae; Kang, Chang Kyung; Lee, Hyo-Jung; Song, Kyoung-Ho; Jae Yoon, Kyung; Paik, Nam-Jong; Seok, Woojin; Yoon, Heejun; Joo, Eun-Jeong; Chang, Yoosoo; Ryu, Seungho; Park, Wan Beom; Su Park, Jeong; Un Park, Kyoung; Ham, Sin Young; Jung, Jongtak; Kim, Eu Suk; Kim, Hong Bin; Ellinghaus, David; Degenhardt, Frauke; Cáceres, Mario; Juzenas, Simonas; Lenz, Tobias L.; Albillos, Agustín; Julià, Antonio; Heidecker, Bettina; Garcia, Federico; Kurth, Florian; Tran, Florian; Hanses, Frank; Zoller, Heinz; Holter, Jan C.; Fernández, Javier; Sander, Leif Erik; Rosenstiel, Philip; Koehler, Philipp; de Cid, Rafael; Asselta, Rosanna; Schreiber, Stefan; Hehr, Ute; Prati, Daniele; Baselli, Guido; Valenti, Luca; Bujanda, Luis; Banales, Jesus M.; Duga, Stefano; D’Amato, Mauro; Romero-Gómez, Manuel; Buti, Maria; Invernizzi, Pietro; Franke, Andre; Hov, Johannes R.; Karlsen, Tom H.; Folseraas, Trine; Maya-Miles, Douglas; Teles, Ana; Azuure, Clinton; Wacker, Eike Matthias; Uellendahl-Werth, Florian; ElAbd, Hesham; Arora, Jatin; Lerga-Jaso, Jon; Wienbrandt, Lars; Rühlemann, Malte Christoph; Wendorff, Mareike; Vadla, May Sissel; Lenning, Ole Bernt; Özer, Onur; Myhre, Ronny; Raychaudhuri, Soumya; Tanck, Anja; Gassner, Christoph; Hemmrich-Stanisak, Georg; Kässens, Jan; Figuera Basso, Maria E.; Schulzky, Martin; Wittig, Michael; Braun, Nicole; Wesse, Tanja; Albrecht, Wolfgang; Yi, Xiaoli; Ortiz, Aaron Blandino; Chercoles, Adolfo Garrido; Ruiz, Agustín; Mantovani, Alberto; Holten, Aleksander Rygh; Mayer, Alena; Cherubini, Alessandro; Protti, Alessandro; Aghemo, Alessio; Gerussi, Alessio; Ramirez, Alfredo; Braun, Alice; Barreira, Ana; Lleo, Ana; Kildal, Anders Benjamin; Glück, Andreas; Nolla, Anna Carreras; Latiano, Anna; Dyrhol-Riise, Anne Ma; Muscatello, Antonio; Voza, Antonio; Rando-Segura, Ariadna; Solier, Aurora; Karina, Banasik; Cortes, Beatriz; Mateos, Beatriz; Nafria-Jimenez, Beatriz; Schaefer, Benedikt; Bellinghausen, Carla; Ferrando, Carlos; Quereda, Carmen; Skurk, Carsten; Thibeault, Charlotte; Spinner, Christoph D.; Lange, Christoph; Hu, Cinzia; Cappadona, Claudio; Bianco, Cristiana; Sancho, Cristina; Lihaug Hoff, Dag Arne; Galimberti, Daniela; Jiménez, David; Pestaña, David; Toapanta, David; Azzolini, Elena; Scarpini, Elio; Helbig, Elisa T.; Urrechaga, Eloisa; Paraboschi, Elvezia Maria; Pontali, Emanuele; Reverter, Enric; Navas, Enrique; Arana, Eunate; Sánchez, Félix García; Ceriotti, Ferruccio; Malvestiti, Francesco; Mesonero, Francisco; Pezzoli, Gianni; Lamorte, Giuseppe; Neb, Holger; My, Ilaria; Hernández, Isabel; de Rojas, Itziar; Galván-Femenia, Iván; Heyckendorf, Jan; Rybniker, Jan; Badia, Joan Ramon; Schneider, Jochen; Goikoetxea, Josune; Kraft, Julia; Müller, Karl Erik; Gaede, Karoline I.; Garcia-Etxebarria, Koldo; Tonby, Kristian; Heggelund, Lars; Izquierdo-Sanchez, Laura; Sumoy, Lauro; Lippert, Lena J.; Terranova, Leonardo; Garbarino, Lucia; Téllez, Luis; Roade, Luisa; Ostadreza, Mahnoosh; Intxausti, Maider; Kogevinas, Manolis; Gutiérrez-Stampa, María A.; Vehreschild, Maria J. G. T.; Marquié, Marta; Castoldi, Massimo; Cecconi, Maurizio; Boada, Mercè; Seilmaier, Michael J.; Mazzocco, Michela; Rodríguez-Gandía, Miguel; Ayo, Natale Imaz; Blay, Natalia; Martínez, Nilda; Cornely, Oliver A.; Palmieri, Orazio; Tentorio, Paolo; Rodrigues, Pedro M.; España, Pedro P.; Hoffmann, Per; Bacher, Petra; Suwalski, Phillip; de Pablo, Raúl; Nieto, Rosa; Badalamenti, Salvatore; Ciesek, Sandra; Bombace, Sara; Wilfling, Sibylle; Brunak, Søren; Heilmann-Heimbach, Stefanie; Ripke, Stephan; Bahmer, Thomas; Landmesser, Ulf; Protzer, Ulrike; Rimoldi, Valeria; Skogen, Vegard; Andrade, Victor; Moreno, Victor; Poller, Wolfgang; Farre, Xavier; Wang, Xiaomin; Khodamoradi, Yascha; Karadeniz, Zehra; de Salazar, Adolfo; Palom, Adriana; Garcia-Fernandez, Alba-Estela; Blanco-Grau, Albert; Zanella, Alberto; Bandera, Alessandra; Nebel, Almut; Biondi, Andrea; Caballero-Garralda, Andrea; Gori, Andrea; Lind, Andreas; Fracanzani, Anna Ludovica; Peschuck, Anna; Pesenti, Antonio; de la Horra, Carmen; Milani, Chiara; Paccapelo, Cinzia; Angelini, Claudio; Cea, Cristina; Muñiz-Diaz, Eduardo; Sandoval, Elena; Calderón, Enrique J.; Solligård, Erik; Aziz, Fátima; Martinelli-Boneschi, Filippo; Peyvandi, Flora; Blasi, Francesco; Medrano, Francisco J.; Rodriguez-Frias, Francisco; Müller, Fredrik; Grasselli, Giacomo; Costantino, Giorgio; Cardamone, Giulia; Foti, Giuseppe; Matullo, Giuseppe; Kurihara, Hayato; Afset, Jan Egil; Damås, Jan Kristian; Ampuero, Javier; Martín, Javier; Erdmann, Jeanette; Bergan, Jonas; Goerg, Siegfried; Ferrusquía-Acosta, Jose; Quero, Jose Hernández; Delgado, Juan; Guerrero, Juan M.; Risnes, Kari; Bettini, Laura Rachele; Moreira, Leticia; Gustad, Lise Tuset; Santoro, Luigi; Scudeller, Luigia; Riveiro-Barciela, Mar; Schaefer, Marco; Carrabba, Maria; Valsecchi, Maria G.; Hernandez-Tejero, María; Acosta-Herrera, Marialbert; D’Angiò, Mariella; Baldini, Marina; Cazzaniga, Marina; Ciccarelli, Michele; Bocciolone, Monica; Miozzo, Monica; Chueca, Natalia; Montano, Nicola; Faverio, Paola; Preatoni, Paoletta; Bonfanti, Paolo; Omodei, Paolo; Castro, Pedro; Ferrer, Ricard; Gualtierotti, Roberta; Gallego-Durán, Rocío; Morilla, Rubén; Haider, Sammra; Marsal, Sara; Aneli, Serena; Pelusi, Serena; Bosari, Silvano; Aliberti, Stefano; Dudman, Susanne; Zheng, Tenghao; Pumarola, Tomas; Cejudo, Trinidad Gonzalez; Monzani, Valter; Friaza, Vicente; Peter, Wolfgang; Dopazo, Ximo; Duga, Stefano; May, Sandra; Grimsrud, Marit M.; Gudbjartsson, Daniel F.; Stefansson, Kari; Sulem, Patrick; Sveinbjornsson, Gardar; Melsted, Pall; Norddahl, Gudmundur; Swerford Moore, Kristjan Helgi; Thorsteinsdottir, Unnur; Holm, Hilma; Alarcón-Riquelme, Marta E.; Bernardo, David; Martínez-Bueno, Manuel; Rello, Silvia Rojo; Magi, Reedik; Milani, Lili; Metspalu, Andres; Laisk, Triin; Läll, Kristi; Lepamets, Maarja; Esko, Tõnu; Reimann, Ene; Naaber, Paul; Laane, Edward; Pesukova, Jaana; Peterson, Pärt; Kisand, Kai; Tabri, Jekaterina; Allos, Raili; Hensen, Kati; Starkopf, Joel; Ringmets, Inge; Tamm, Anu; Kallaste, Anne; Alavere, Helene; Metsalu, Kristjan; Puusepp, Mairo; Kristiansson, Kati; Koskelainen, Sami; Perola, Markus; Donner, Kati; Kivinen, Katja; Palotie, Aarno; Palotie, Aarno; Rivolta, Carlo; Bochud, Pierre-Yves; Bibert, Stéphanie; Boillat, Noémie; Nussle, Semira Gonseth; Albrich, Werner; Quinodoz, Mathieu; Kamdar, Dhryata; Suh, Noémie; Neofytos, Dionysios; Erard, Véronique; Voide, Cathy; Bochud, P. Y.; Rivolta, C.; Bibert, S.; Quinodoz, M.; Kamdar, D.; Neofytos, D.; Erard, V.; Voide, C.; Friolet, R.; Vollenweider, P.; Pagani, J. L.; Oddo, M.; zu Bentrup, F. Meyer; Conen, A.; Clerc, O.; Marchetti, O.; Guillet, A.; Guyat-Jacques, C.; Foucras, S.; Rime, M.; Chassot, J.; Jaquet, M.; Viollet, R. Merlet; Lannepoudenx, Y.; Portopena, L.; Desgranges, F.; Filippidis, P.; Guéry, B.; Haefliger, D.; Kampouri, E. E.; Manuel, O.; Munting, A.; Papadimitriou-Olivgeris, M.; Regina, J.; Rochat-Stettler, L.; Suttels, V.; Tadini, E.; Tschopp, J.; Van Singer, M.; Viala, B.; Boillat-Blanco, N.; Brahier, T.; Hügli, O.; Meuwly, J. Y.; Pantet, O.; Nussle, S. Gonseth; Bochud, M.; D’Acremont, V.; Younes, S. Estoppey; Albrich, W. C.; Suh, N.; Cerny, A.; O’Mahony, L.; von Mering, C.; Bochud, P. Y.; Frischknecht, M.; Kleger, G.-R.; Filipovic, M.; Kahlert, C. R.; Wozniak, H.; Negro, T. Rochat; Pugin, J.; Bouras, K.; Knapp, C.; Egger, T.; Perret, A.; Montillier, P.; di Bartolomeo, C.; Barda, B.; de Cid, Rafael; Carreras, Anna; Moreno, Victor; Galván-Femenía, Iván; Blay, Natalia; Farré, Xavier; Sumoy, Lauro; Cortés, Beatriz; Mercader, Josep Maria; Guindo-Martinez, Marta; Torrents, David; Garcia-Aymerich, Judith; Castaño-Vinyals, Gemma; Dobaño, Carlota; Gori, Marco; Renieri, Alessandra; Mondelli, Mario Umberto; Castelli, Francesco; Vaghi, Massimo; Rusconi, Stefano; Montagnani, Francesca; Bargagli, Elena; Franchi, Federico; Mazzei, Maria Antonietta; Cantarini, Luca; Tacconi, Danilo; Feri, Marco; Scala, Raffaele; Spargi, Genni; Nencioni, Cesira; Bandini, Maria; Caldarelli, Gian Piero; Spagnesi, Maurizio; Canaccini, Anna; Ognibene, Agostino; D’Arminio Monforte, Antonella; Girardis, Massimo; Antinori, Andrea; Francisci, Daniela; Schiaroli, Elisabetta; Scotton, Pier Giorgio; Panese, Sandro; Scaggiante, Renzo; Monica, Matteo Della; Capasso, Mario; Fiorentino, Giuseppe; Castori, Marco; Aucella, Filippo; Di Biagio, Antonio; Masucci, Luca; Valente, Serafina; Mandalà, Marco; Zucchi, Patrizia; Giannattasio, Ferdinando; Coviello, Domenico A.; Mussini, Cristina; Bosio, Giancarlo; Tavecchia, Luisa; Crotti, Lia; Rizzi, Marco; La Rovere, Maria Teresa; Sarzi-Braga, Simona; Bussotti, Maurizio; Ravaglia, Sabrina; Artuso, Rosangela; Perrella, Antonio; Romani, Davide; Bergomi, Paola; Catena, Emanuele; Vincenti, Antonella; Ferri, Claudio; Grassi, Davide; Pessina, Gloria; Tumbarello, Mario; Di Pietro, Massimo; Sabrina, Ravaglia; Luchi, Sauro; Barbieri, Chiara; Acquilini, Donatella; Andreucci, Elena; Paciosi, Francesco; Segala, Francesco Vladimiro; Tiseo, Giusy; Falcone, Marco; Lista, Mirjam; Poscente, Monica; De Vivo, Oreste; Petrocelli, Paola; Guarnaccia, Alessandra; Baroni, Silvia; Perticaroli, Valentina; Furini, Simone; Dei, Simona; Benetti, Elisa; Picchiotti, Nicola; Sanarico, Maurizio; Ceri, Stefano; Pinoli, Pietro; Raimondi, Francesco; Biscarini, Filippo; Stella, Alessandra; Bergomi, Mattia; Zguro, Kristina; Capitani, Katia; Tanfoni, Marco; Fallerini, Chiara; Daga, Sergio; Baldassarri, Margherita; Fava, Francesca; Frullanti, Elisa; Valentino, Floriana; Doddato, Gabriella; Giliberti, Annarita; Tita, Rossella; Amitrano, Sara; Bruttini, Mirella; Croci, Susanna; Meloni, Ilaria; Mencarelli, Maria Antonietta; Lo Rizzo, Caterina; Pinto, Anna Maria; Beligni, Giada; Tommasi, Andrea; Di Sarno, Laura; Palmieri, Maria; Carriero, Miriam Lucia; Alaverdian, Diana; Iuso, Nicola; Inchingolo, Gabriele; Busani, Stefano; Bruno, Raffaele; Vecchia, Marco; Belli, Mary Ann; Mantovani, Stefania; Ludovisi, Serena; Quiros-Roldan, Eugenia; Antoni, Melania Degli; Zanella, Isabella; Siano, Matteo; Emiliozzi, Arianna; Fabbiani, Massimiliano; Rossetti, Barbara; Zanelli, Giacomo; Bergantini, Laura; D’Alessandro, Miriana; Cameli, Paolo; Bennet, David; Anedda, Federico; Marcantonio, Simona; Scolletta, Sabino; Guerrini, Susanna; Conticini, Edoardo; Frediani, Bruno; Spertilli, Chiara; Donati, Alice; Guidelli, Luca; Corridi, Marta; Croci, Leonardo; Piacentini, Paolo; Desanctis, Elena; Cappelli, Silvia; Verzuri, Agnese; Anemoli, Valentina; Pancrazi, Alessandro; Lorubbio, Maria; Merlini, Esther; Miraglia, Federica Gaia; Venturelli, Sophie; Cossarizza, Andrea; Vergori, Alessandra; Gabrieli, Arianna; Riva, Agostino; Paciosi, Francesco; Andretta, Francesca; Gatti, Francesca; Parisi, Saverio Giuseppe; Baratti, Stefano; Piscopo, Carmelo; Russo, Roberta; Andolfo, Immacolata; Iolascon, Achille; Carella, Massimo; Merla, Giuseppe; Squeo, Gabriella Maria; Raggi, Pamela; Marciano, Carmen; Perna, Rita; Bassetti, Matteo; Sanguinetti, Maurizio; Giorli, Alessia; Salerni, Lorenzo; Parravicini, Pierpaolo; Menatti, Elisabetta; Trotta, Tullio; Coiro, Gabriella; Lena, Fabio; Martinelli, Enrico; Mancarella, Sandro; Gabbi, Chiara; Maggiolo, Franco; Ripamonti, Diego; Bachetti, Tiziana; Suardi, Claudia; Parati, Gianfranco; Bottà, Giordano; Di Domenico, Paolo; Rancan, Ilaria; Bianchi, Francesco; Colombo, Riccardo; van Heel, David A.; Hunt, Karen A.; Trembath, Richard C.; Huang, Qin Qin; Martin, Hilary C.; Mason, Dan; Trivedi, Bhavi; Wright, John; Finer, Sarah; Griffiths, Christopher J.; Akhtar, Shaheen; Anwar, Mohammad; Arciero, Elena; Ashraf, Samina; Breen, Gerome; Chung, Raymond; Curtis, Charles J.; Chowdhury, Maharun; Colligan, Grainne; Deloukas, Panos; Durham, Ceri; Finer, Sarah; Griffiths, Chris; Huang, Qin Qin; Hurles, Matt; Hunt, Karen A.; Hussain, Shapna; Islam, Kamrul; Khan, Ahsan; Khan, Amara; Lavery, Cath; Lee, Sang Hyuck; Lerner, Robin; MacArthur, Daniel; MacLaughlin, Bev; Martin, Hilary; Mason, Dan; Miah, Shefa; Newman, Bill; Safa, Nishat; Tahmasebi, Farah; Trembath, Richard C.; Trivedi, Bhavi; van Heel, David A.; Wright, John; Smith, Albert V.; Boughton, Andrew P.; Li, Kevin W.; LeFaive, Jonathon; Annis, Aubrey; Jannes, Cinthia E.; Krieger, Jose E.; Pereira, Alexandre C.; Velho, Mariliza; Marques, Emanuelle; Lima, Isabella Ramos; Tada, Mauricio Teruo; Valino, Karina; McCarthy, Mark; Rosenberger, Carrie; Lee, Jon
Whole-genome sequencing reveals host factors underlying critical COVID-19
No full text: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Whole-genome sequencing reveals host factors underlying critical COVID-19
No full textAltres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19
No full textThe COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p
