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1. PNPLA3 as a therapeutic target for fatty liver disease: the evidence to date

Author

Alessandro Cherubini, Elia Casirati, Melissa Tomasi, and Luca Valenti

Subjects
Pharmacology, Genotype, Liver, Non-alcoholic Fatty Liver Disease, Clinical Biochemistry, Drug Discovery, Humans, Membrane Proteins, Molecular Medicine, Genetic Predisposition to Disease, Lipase, Polymorphism, Single Nucleotide
Abstract

An interaction between metabolic triggers and inherited predisposition underpins the development and progression of non alcoholic fatty liver disease (NAFLD) and fatty liver disease in general. Among the specific NAFLD risk variants,The scope of this review is to briefly describe the PNPLA3 gene and protein function before discussing therapeutic approaches for fatty liver aiming at this target. Literature review was carried out searching through PubMed and clinicaltrials.gov website and focusing on the most recent works and reviews.The main therapeutic strategies under development for NAFLD have shown variable efficacy and side-effects likely due to disease heterogeneity and lack of engagement of the main pathogenic drivers of liver disease. To overcome these limitations, new strategies are becoming available for targeting

Published
2021
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2. Circulating Interlukin-32 and Altered Blood Pressure Control in Individuals with Metabolic Dysfunction

Author

Melissa Tomasi, Alessandro Cherubini, Serena Pelusi, Sara Margarita, Cristiana Bianco, Francesco Malvestiti, Lorenzo Miano, Stefano Romeo, Daniele Prati, and Luca Valenti

Subjects
Inorganic Chemistry, Organic Chemistry, arterial hypertension, hepatic fat accumulation, IL-32, inflammation, MAFLD, NAFLD, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract

Fatty liver disease is most frequently related to metabolic dysfunction (MAFLD) and associated comorbidities, heightening the risk of cardiovascular disease, and is associated with higher hepatic production of IL32, a cytokine linked with lipotoxicity and endothelial activation. The aim of this study was to examine the relationship between circulating IL32 concentration and blood pressure control in individuals with metabolic dysfunction at high risk of MAFLD. IL32 plasma levels were measured by ELISA in 948 individuals with metabolic dysfunction enrolled in the Liver-Bible-2021 cohort. Higher circulating IL32 levels were independently associated with systolic blood pressure (estimate +0.008 log10 per 1 mmHg increase, 95% c.i. 0.002–0.015; p = 0.016), and inversely correlated with antihypertensive medications (estimate −0.189, 95% c.i. −0.291–−0.088, p = 0.0002). Through multivariable analysis, IL32 levels predicted both systolic blood pressure (estimate 0.746, 95% c.i 0.173–1.318; p = 0.010) and impaired blood pressure control (OR 1.22, 95% c.i. 1.09–1.38; p = 0.0009) independently of demographic and metabolic confounders and of treatment. This study reveals that circulating IL32 levels are associated with impaired blood pressure control in individuals at risk of cardiovascular disease.

Published
2023
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3. Increased burden of inherited IRF3 rare genetic variants in Europeans with severe Non-alcoholic fatty liver diease

Author

Luigi Santoro, Daniele Marchelli, Alessandro Cherubini, Elia Casirati, Francesco Malvestiti, Melissa Tomasi, Paola Dongiovanni, Cristiana Bianco, Marica Meroni, Alessandro Federico, Salvatore Petta, Elisabetta Bugianesi, Giorgio Soardo, Umberto Vespasiani Gentilucci, Luca Miele, Helen Reeves, Daniele Prati, Luisa Ronzoni, Giodo Baselli, and Luca Valenti

Subjects
Hepatology, N/A, Settore MED/12 - GASTROENTEROLOGIA
Published
2022

4. Rare ATG7 genetic variants predispose patients to severe fatty liver disease

Author

Guido A. Baselli, Oveis Jamialahmadi, Serena Pelusi, Ester Ciociola, Francesco Malvestiti, Marco Saracino, Luigi Santoro, Alessandro Cherubini, Paola Dongiovanni, Marco Maggioni, Cristiana Bianco, Federica Tavaglione, Annalisa Cespiati, Rosellina M. Mancina, Roberta D’Ambrosio, Valentina Vaira, Salvatore Petta, Luca Miele, Umberto Vespasiani-Gentilucci, Alessandro Federico, Jussi Pihlajamaki, Elisabetta Bugianesi, Anna L. Fracanzani, Helen L. Reeves, Giorgio Soardo, Daniele Prati, Stefano Romeo, Luca VC. Valenti, Vittorio Borroni, Antonio Liguori, Luisa Ronzoni, Melissa Tomasi, Angela Lombardi, Mahnoosh Ostadreza, Elia Casirati, Ilaria Marini, Silvia Maier, Chiara Rosso, Gianluca Svegliati Baroni, Carlo Santaniello, Marcello Dallio, Baselli, Guido A, Jamialahmadi, Ovei, Pelusi, Serena, Ciociola, Ester, Malvestiti, Francesco, Saracino, Marco, Santoro, Luigi, Cherubini, Alessandro, Dongiovanni, Paola, Maggioni, Marco, Bianco, Cristiana, Tavaglione, Federica, Cespiati, Annalisa, Mancina, Rosellina M, D'Ambrosio, Roberta, Vaira, Valentina, Petta, Salvatore, Miele, Luca, Vespasiani-Gentilucci, Umberto, Federico, Alessandro, Pihlajamaki, Jussi, Bugianesi, Elisabetta, Fracanzani, Anna L, Reeves, Helen L, Soardo, Giorgio, Prati, Daniele, Romeo, Stefano, and Valenti, Luca Vc

Subjects
Inflammation, Liver Cirrhosis, autophagy, Hepatology, Biopsy, NAFLD, NASH, autophagy, genetics, liver fibrosis, Carcinoma, Liver Neoplasms, NASH, Hepatocellular, Autophagy-Related Protein 7, NAFLD, genetics, liver fibrosis, Humans, Liver, Carcinoma, Hepatocellular, Non-alcoholic Fatty Liver Disease, genetic
Abstract

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.Methods: We performed whole-exome sequencing in in-dividuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p = 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p = 0.003), predisposed to hepatocellular ballooning (p = 0.007) evolving to fibrosis in the Liver biopsy cohort (n = 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p

Published
2022

5. Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Author

Michela Mazzocco, Giuseppe Lamorte, Leonardo Terranova, Cinzia Hu, Xavier Farré, Yascha Khodamoradi, Mauro D'Amato, Christian Herr, David Jiménez, Filippo Martinelli-Boneschi, Anna Latiano, Michael Dreher, Mariella D'Angiò, Rossana Carpani, Francesco Malvestiti, Enrique Navas, Antonio Voza, Anne Ma Dyrhol-Riise, Karina Banasik, Juan Delgado, Florian Kurth, Trinidad Gonzalez Cejudo, Lars Wienbrandt, Carmen de la Horrra, May Sissel Vadla, Aurora Solier, Koldo Garcia-Etxebarria, Karoline I. Gaede, Wolfgang Poller, Eloisa Urrechaga, Paolo Bonfanti, Philipp Schommers, Giuseppe Bellelli, Zehra Karadeniz, Jan Kristian Rybniker, Lisa Knopp, Alfredo Ramirez, Jesus M. Banales, Sibylle Wilfling, Elio Scarpini, Alberto Zanella, Anna Carreras Nolla, Joaquín Dopazo, Sara Pigazzini, Nicole Ludwig, Ingo Kurth, Sandra Ciesek, Dag Arne Lihaug Hoff, Ernesto Contro, Giacomo Grasselli, Maider Intxausti, Kari Risnes, Francisco Mesonero, Thorsten Brenner, Lena J Lippert, Adolfo de Salazar, Maria A. Gutierrez-Stampa, Aaron Blandino Ortiz, María Hernández-Tejero, Rosa Nieto, Jochen Schneider, Anke Hinney, Chiara Scollo, Ariadna Rando-Segura, Victor Moreno, Phillip Suwalski, Valeria Rimoldi, Ricard Ferrer, Jon Lerga-Jaso, Claudio Cappadona, Janine Altmueller, Mahnoosh Ostadreza, Verena Keitel, Lauro Sumoy, Eunate Arana, Annalisa Cavallero, Massimo Castoldi, Stephan Ripke, Antonio Muscatello, Maria J G T Vehreschild, Michael Wittig, Robert Bals, Verena Kopfnagel, David Haschka, Luis Téllez, Heinz Zoller, Isabel Hernández, Carla Bellinghausen, Agustín Ruiz, Manuel Romero-Gómez, Malte C. Ruehlemann, Nikolaus Marx, Luigi Santoro, Silvano Bosari, Carlos Ferrando, M.A. Rodríguez-Gandía, Ronny Myhre, Aleksander Rygh Holten, Marina Elena Cazzaniga, Andreas Lind, Pedro M. Rodrigues, Giacomo Bellani, Alice Braun, Clara Lehmann, Anna Ludovica Fracanzani, Soumya Raychaudhuri, Trine Folseraas, Kerstin U. Ludwig, Lindokuhle Nkambule, Gianni Pezzoli, Julia Kraft, Rocío Gallego-Durán, David Ellinghaus, Rosanna Asselta, Simonas Juzenas, Max Augustin, Mari Niemi, Manolis Kogevinas, Carlo Maj, Serena Pelusi, Stefano Aliberti, Rafael de Cid, Selina Rolker, Victor Andrade, Jonas Bergan, Federico García, Tobias L. Lenz, Andrea Gori, Maria Grazia Valsecchi, Elisa T Helbig, Oliver A. Cornely, Laura Izquierdo-Sanchez, Tom H. Karlsen, Adolfo Garrido Chercoles, Joan Ramon Badia, José Hernández Quero, Benedikt Schaefer, Jatin Arora, Mareike Wendorff, David Pestaña, Thomas Bahmer, Ana Teles, Antonella Ruello, Alessio Gerussi, Francisco J. Medrano, Xiaomin Wang, Joern Walter, Natale Imaz Ayo, Onur oezer, Almut Nebel, Ferruccio Ceriotti, Mercè Boada, Ulf Landmesser, Ana Lleo, Christoph D. Spinner, Sara Bombace, Giuseppe Foti, Antonio Julià, Alessandro Cherubini, Lucia Garbarino, Beatriz Nafria-Jimenez, Hesham ElAbd, Pietro Invernizzi, Paola Faverio, Jordi Barretina, David Toapanta, Iván Galván-Femenía, Sara Marsal, Stefano Duga, Ulrike Protzer, Luisa Roade, Philipp Koehler, Nilda Martinez, Clinton Azuure, Philip Rosenstiel, Daniela Galimberti, Per Hoffmann, Alessandra Bandera, Natalia Blay, Jan Cato Holter, Julia Fazaal, Eike Matthias Wacker, Torsten Feldt, Giovanni Albano, Andre Franke, Mario Cáceres, Roberta Gualtierotti, Sebastian J. Klein, Andreas Glueck, Salvatore Badalamenti, Siegfried Goerg, Isabell Pink, Stefan Schreiber, Leif E. Sander, Javier Fernández, M Seilmaier, Orazio Palmieri, Carsten Skurk, Jan Heyckendorf, Adriana Palom, Stefanie Heilmann-Heimbach, Francesco Blasi, Ilaria My, Mattia Cordioli, Sammra Haider, Giorgio Costantino, Giuseppe Citerio, Nicola Montano, Pedro Castro, Marit Mæhle Grimsrud, Alexander Popov, Ole Bernt Lenning, Holger Neb, Enric Reverter, Erik Solligård, Oliver Witzke, Itziar de Rojas, Flora Peyvandi, Susanne Gjeruldsen Dudman, Daniele Prati, Kristian Tonby, Luca Valenti, Christoph Lange, Alberto Mantovani, Florian Tran, Juan M. Guerrero, Luis Bujanda, Natalia Chueca, Michael Joannidis, Enrique J. Calderon, Elvezia Maria Paraboschi, Vegard Skogen, Bjoern Jensen, Paolo Tentorio, Raúl de Pablo, Cristiana Bianco, Antonio Pesenti, Vicente Friaza, Lars Heggelund, Eva C. Schulte, Markus M. Noethen, Andrea Ganna, Agustín Albillos, Laura Rachele Bettini, Florian Uellendahl-Werth, Covid Aachen Study, Josune Goikoetxea, Jan Kristian Damås, Andrea Biondi, Cristina Sancho, Alessandro Protti, Bettina Heidecker, Ute Hehr, Markus Cornberg, Lise Tuset Gustad, Ana Barreira, Emanuele Pontali, Felix Garcia Sanchez, Johannes R. Hov, Marta Marquié, Maria Buti, Sandra May, Melissa Tomasi, Javier Ampuero, Søren Brunak, Carmen Quereda, Pedro Pablo Espana, Beatriz Mateos, Jan Egil Afset, Mar Riveiro-Barciela, Beatriz Cortés, Thomas Eggermann, Frank Hanses, Julia Schroeder, Karl Erik Mueller, Maria Manunta, Anders Benjamin Kildal, Thomas Illig, Charlotte Thibeault, Maurizio Cecconi, Alena Mayer, Frauke Degenhardt, Douglas Maya-Miles, Alessio Aghemo, Petra Bacher, Marc M. Berger, Francisco Rodriguez-Frias, Fredrik Mueller, Elena Azzolini, Ruben Morilla, Federal Ministry of Education and Research (Germany), German Research Foundation, Novo Nordisk Foundation, Ministero della Salute, European Commission, Fondazione Cariplo, Ministero dell'Istruzione, dell'Università e della Ricerca, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación 'la Caixa', Eusko Jaurlaritza, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Norwegian Research Council, German Center for Lung Research, Airway Research Center North (Germany), Miltenyi Biotec, University of Cologne, Technical University of Munich, Finnish Institute for Molecular Medicine, University of Helsinki, Saarland University, University Hospital Bonn, Bavarian State Ministry of Education, Science and the Arts, Essen University Hospital, Degenhardt, F, Ellinghaus, D, Juzenas, S, Lerga-Jaso, J, Wendorff, M, Maya-Miles, D, Uellendahl-Werth, F, Elabd, H, Rühlemann, M, Arora, J, Özer, O, Lenning, O, Myhre, R, Vadla, M, Wacker, E, Wienbrandt, L, Ortiz, A, Salazar, A, Chercoles, A, Palom, A, Ruiz, A, Garcia-Fernandez, A, Blanco-Grau, A, Mantovani, A, Zanella, A, Holten, A, Mayer, A, Bandera, A, Cherubini, A, Protti, A, Aghemo, A, Gerussi, A, Ramirez, A, Braun, A, Nebel, A, Barreira, A, Lleo, A, Teles, A, Kildal, A, Biondi, A, Caballero-Garralda, A, Ganna, A, Gori, A, Glück, A, Lind, A, Tanck, A, Hinney, A, Nolla, A, Fracanzani, A, Peschuck, A, Cavallero, A, Dyrhol-Riise, A, Ruello, A, Julià, A, Muscatello, A, Pesenti, A, Voza, A, Rando-Segura, A, Solier, A, Schmidt, A, Cortes, B, Mateos, B, Nafria-Jimenez, B, Schaefer, B, Jensen, B, Bellinghausen, C, Maj, C, Ferrando, C, Horra, C, Quereda, C, Skurk, C, Thibeault, C, Scollo, C, Herr, C, Spinner, C, Gassner, C, Lange, C, Hu, C, Paccapelo, C, Lehmann, C, Angelini, C, Cappadona, C, Azuure, C, Bianco, C, Cea, C, Sancho, C, Hoff, D, Galimberti, D, Prati, D, Haschka, D, Jiménez, D, Pestaña, D, Toapanta, D, Muñiz-Diaz, E, Azzolini, E, Sandoval, E, Binatti, E, Scarpini, E, Helbig, E, Casalone, E, Urrechaga, E, Paraboschi, E, Pontali, E, Reverter, E, Calderón, E, Navas, E, Solligård, E, Contro, E, Arana-Arri, E, Aziz, F, Garcia, F, Sánchez, F, Ceriotti, F, Martinelli-Boneschi, F, Peyvandi, F, Kurth, F, Blasi, F, Malvestiti, F, Medrano, F, Mesonero, F, Rodriguez-Frias, F, Hanses, F, Müller, F, Hemmrich-Stanisak, G, Bellani, G, Grasselli, G, Pezzoli, G, Costantino, G, Albano, G, Cardamone, G, Bellelli, G, Citerio, G, Foti, G, Lamorte, G, Matullo, G, Baselli, G, Kurihara, H, Neb, H, My, I, Kurth, I, Hernández, I, Pink, I, Rojas, I, Galván-Femenia, I, Holter, J, Afset, J, Heyckendorf, J, Kässens, J, Damås, J, Rybniker, J, Altmüller, J, Ampuero, J, Martín, J, Erdmann, J, Banales, J, Badia, J, Dopazo, J, Schneider, J, Bergan, J, Barretina, J, Walter, J, Quero, J, Goikoetxea, J, Delgado, J, Guerrero, J, Fazaal, J, Kraft, J, Schröder, J, Risnes, K, Banasik, K, Müller, K, Gaede, K, Garcia-Etxebarria, K, Tonby, K, Heggelund, L, Izquierdo-Sanchez, L, Bettini, L, Sumoy, L, Sander, L, Lippert, L, Terranova, L, Nkambule, L, Knopp, L, Gustad, L, Garbarino, L, Santoro, L, Téllez, L, Roade, L, Ostadreza, M, Intxausti, M, Kogevinas, M, Riveiro-Barciela, M, Berger, M, Schaefer, M, Niemi, M, Gutiérrez-Stampa, M, Carrabba, M, Figuera Basso, M, Valsecchi, M, Hernandez-Tejero, M, Vehreschild, M, Manunta, M, Acosta-Herrera, M, D'Angiò, M, Baldini, M, Cazzaniga, M, Grimsrud, M, Cornberg, M, Nöthen, M, Marquié, M, Castoldi, M, Cordioli, M, Cecconi, M, D'Amato, M, Augustin, M, Tomasi, M, Boada, M, Dreher, M, Seilmaier, M, Joannidis, M, Wittig, M, Mazzocco, M, Ciccarelli, M, Rodríguez-Gandía, M, Bocciolone, M, Miozzo, M, Ayo, N, Blay, N, Chueca, N, Montano, N, Braun, N, Ludwig, N, Marx, N, Martínez, N, Cornely, O, Witzke, O, Palmieri, O, Faverio, P, Preatoni, P, Bonfanti, P, Omodei, P, Tentorio, P, Castro, P, Rodrigues, P, España, P, Hoffmann, P, Rosenstiel, P, Schommers, P, Suwalski, P, Pablo, R, Ferrer, R, Bals, R, Gualtierotti, R, Gallego-Durán, R, Nieto, R, Carpani, R, Morilla, R, Badalamenti, S, Haider, S, Ciesek, S, May, S, Bombace, S, Marsal, S, Pigazzini, S, Klein, S, Pelusi, S, Wilfling, S, Bosari, S, Volland, S, Brunak, S, Raychaudhuri, S, Schreiber, S, Heilmann-Heimbach, S, Aliberti, S, Ripke, S, Dudman, S, Wesse, T, Zheng, T, Bahmer, T, Eggermann, T, Illig, T, Brenner, T, Pumarola, T, Feldt, T, Folseraas, T, Cejudo, T, Landmesser, U, Protzer, U, Hehr, U, Rimoldi, V, Monzani, V, Skogen, V, Keitel, V, Kopfnagel, V, Friaza, V, Andrade, V, Moreno, V, Albrecht, W, Peter, W, Poller, W, Farre, X, Yi, X, Wang, X, Khodamoradi, Y, Karadeniz, Z, Latiano, A, Goerg, S, Bacher, P, Koehler, P, Tran, F, Zoller, H, Schulte, E, Heidecker, B, Ludwig, K, Fernández, J, Romero-Gómez, M, Albillos, A, Invernizzi, P, Buti, M, Duga, S, Bujanda, L, Hov, J, Lenz, T, Asselta, R, Cid, R, Valenti, L, Karlsen, T, Cáceres, M, Franke, A, Data Science Genetic Epidemiology Lab, and Institute for Molecular Medicine Finland

Subjects
Settore MED/09 - Medicina Interna, Population, Medizin, Genome-wide association study, Human leukocyte antigen, Biology, Genoma humà, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Medisinske Fag: 700 [VDP], ddc:570, Genetics, GWAS, Humans, genetics [COVID-19], education, Molecular Biology, Gene, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, Polymorphism, Genetic, Human genome, SARS-CoV-2, GWAS, COVID-19, 1184 Genetics, developmental biology, physiology, Chromosome, COVID-19, genetics [SARS-CoV-2], General Medicine, 3. Good health, GWAS analysis, Respiratory failure, Haplotypes, NAPSA, Technology Platforms, Genètica, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung., Andre Franke and David Ellinghaus were supported by a grant from the German Federal Ministry of Education and Research (01KI20197), Andre Franke, David Ellinghaus and Frauke Degenhardt were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). David Ellinghaus was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). David Ellinghaus, Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grant NNF14CC0001 and NNF17OC0027594). Tobias L. Lenz, Ana Teles and Onur Özer were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. Mareike Wendorff and Hesham ElAbd are supported by the German Research Foundation (DFG) through the Research Training Group 1743, "Genes, Environment and Inflammation". This project was supported by a Covid-19 grant from the German Federal Ministry of Education and Research (BMBF; ID: 01KI20197). Luca Valenti received funding from: Ricerca Finalizzata Ministero della Salute RF2016-02364358, Italian Ministry of Health ""CV PREVITAL – strategie di prevenzione primaria cardiovascolare primaria nella popolazione italiana; The European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- and for the project ""REVEAL""; Fondazione IRCCS Ca' Granda ""Ricerca corrente"", Fondazione Sviluppo Ca' Granda ""Liver-BIBLE"" (PR-0391), Fondazione IRCCS Ca' Granda ""5permille"" ""COVID-19 Biobank"" (RC100017A). Andrea Biondi was supported by the grant from Fondazione Cariplo to Fondazione Tettamanti: "Biobanking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by a MIUR grant to the Department of Medical Sciences, under the program "Dipartimenti di Eccellenza 2018–2022". This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia, Fundació IGTP. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIIIMINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529). Marta Marquié received research funding from ant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa")., Beatriz Cortes is supported by national grants PI18/01512. Xavier Farre is supported by VEIS project (001-P-001647) (cofunded by European Regional Development Fund (ERDF), “A way to build Europe”). Additional data included in this study was obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, EIT COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. Antonio Julià and Sara Marsal were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). Antonio Julià was also supported the by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the FEDER. The Basque Biobank is a hospitalrelated platform that also involves all Osakidetza health centres, the Basque government's Department of Health and Onkologikoa, is operated by the Basque Foundation for Health Innovation and Research-BIOEF. Mario Cáceres received Grants BFU2016-77244-R and PID2019-107836RB-I00 funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU). Manuel Romero Gómez, Javier Ampuero Herrojo, Rocío Gallego Durán and Douglas Maya Miles are supported by the “Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III” (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100), and by the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018, COVID-Premed, COVID GWAs). The position held by Itziar de Rojas Salarich is funded by grant FI20/00215, PFIS Contratos Predoctorales de Formación en Investigación en Salud. Enrique Calderón's team is supported by CIBER of Epidemiology and Public Health (CIBERESP), "Instituto de Salud Carlos III". Jan Cato Holter reports grants from Research Council of Norway grant no 312780 during the conduct of the study. Dr. Solligård: reports grants from Research Council of Norway grant no 312769. The BioMaterialBank Nord is supported by the German Center for Lung Research (DZL), Airway Research Center North (ARCN). The BioMaterialBank Nord is member of popgen 2.0 network (P2N). Philipp Koehler has received non-financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. He is supported by the German Federal Ministry of Education and Research (BMBF)., Oliver A. Cornely is supported by the German Federal Ministry of Research and Education and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – CECAD, EXC 2030 – 390661388. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping was performed by the Genotyping laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. Kerstin U. Ludwig is supported by the German Research Foundation (DFG, LU-1944/3-1). Genotyping for the BoSCO study is funded by the Institute of Human Genetics, University Hospital Bonn. Frank Hanses was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to Alfredo Ramirez from the German Federal Ministry of Education and Research (BMBF, grant: 01ED1619A, European Alzheimer DNA BioBank, EADB) within the context of the EU Joint Programme – Neurodegenerative Disease Research (JPND). Additional funding was derived from the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. Philip Rosenstiel is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). Florian Tran is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). Christoph Lange and Jan Heyckendorf are supported by the German Center for Infection Research (DZIF). Thorsen Brenner, Marc M Berger, Oliver Witzke und Anke Hinney are supported by the Stiftung Universitätsmedizin Essen. Marialbert Acosta-Herrera was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. Eva C Schulte is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).

Published
2022
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