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

  1. Frauke Degenhardt
  2. David Ellinghaus
  3. Simonas Juzenas
  4. Jon Lerga-Jaso
  5. Mareike Wendorff
  6. Douglas Maya-Miles
  7. Florian Uellendahl-Werth
  8. Hesham ElAbd
  9. Malte C RĂĽhlemann
  10. Jatin Arora
  11. Onur Ă–zer
  12. Ole Bernt Lenning
  13. Ronny Myhre
  14. May Sissel Vadla
  15. Eike M Wacker
  16. Lars Wienbrandt
  17. Aaron Blandino Ortiz
  18. Adolfo de Salazar
  19. Adolfo Garrido Chercoles
  20. Adriana Palom
  21. AgustĂ­n Ruiz
  22. Alba-Estela Garcia-Fernandez
  23. Albert Blanco-Grau
  24. Alberto Mantovani
  25. Alberto Zanella
  26. Aleksander Rygh Holten
  27. Alena Mayer
  28. Alessandra Bandera
  29. Alessandro Cherubini
  30. Alessandro Protti
  31. Alessio Aghemo
  32. Alessio Gerussi
  33. Alfredo Ramirez
  34. Alice Braun
  35. Almut Nebel
  36. Ana Barreira
  37. Ana Lleo
  38. Ana Teles
  39. Anders Benjamin Kildal
  40. Andrea Biondi
  41. Andrea Caballero-Garralda
  42. Andrea Ganna
  43. Andrea Gori
  44. Andreas GlĂĽck
  45. Andreas Lind
  46. Anja Tanck
  47. Anke Hinney
  48. Anna Carreras Nolla
  49. Anna Ludovica Fracanzani
  50. Anna Peschuck
  51. Annalisa Cavallero
  52. Anne Ma Dyrhol-Riise
  53. Antonella Ruello
  54. Antonio JuliĂ 
  55. Antonio Muscatello
  56. Antonio Pesenti
  57. Antonio Voza
  58. Ariadna Rando-Segura
  59. Aurora Solier
  60. Axel Schmidt
  61. Beatriz Cortes
  62. Beatriz Mateos
  63. Beatriz Nafria-Jimenez
  64. Benedikt Schaefer
  65. Björn Jensen
  66. Carla Bellinghausen
  67. Carlo Maj
  68. Carlos Ferrando
  69. Carmen de la Horra
  70. Carmen Quereda
  71. Carsten Skurk
  72. Charlotte Thibeault
  73. Chiara Scollo
  74. Christian Herr
  75. Christoph D Spinner
  76. Christoph Gassner
  77. Christoph Lange
  78. Cinzia Hu
  79. Cinzia Paccapelo
  80. Clara Lehmann
  81. Claudio Angelini
  82. Claudio Cappadona
  83. Clinton Azuure
  84. COVICAT study group
  85. Covid-19 Aachen Study (COVAS)
  86. Cristiana Bianco
  87. Cristina Cea
  88. Cristina Sancho
  89. Dag Arne Lihaug Hoff
  90. Daniela Galimberti
  91. Daniele Prati
  92. David Haschka
  93. David Jiménez
  94. David Pestaña
  95. David Toapanta
  96. Eduardo Muñiz-Diaz
  97. Elena Azzolini
  98. Elena Sandoval
  99. Eleonora Binatti
  100. Elio Scarpini
  101. Elisa T Helbig
  102. Elisabetta Casalone
  103. Eloisa Urrechaga
  104. Elvezia Maria Paraboschi
  105. Emanuele Pontali
  106. Enric Reverter
  107. Enrique J CalderĂłn
  108. Enrique Navas
  109. Erik SolligĂĄrd
  110. Ernesto Contro
  111. Eunate Arana-Arri
  112. Fátima Aziz
  113. Federico Garcia
  114. Félix García Sánchez
  115. Ferruccio Ceriotti
  116. Filippo Martinelli-Boneschi
  117. Flora Peyvandi
  118. Florian Kurth
  119. Francesco Blasi
  120. Francesco Malvestiti
  121. Francisco J Medrano
  122. Francisco Mesonero
  123. Francisco Rodriguez-Frias
  124. Frank Hanses
  125. Fredrik MĂĽller
  126. Georg Hemmrich-Stanisak
  127. Giacomo Bellani
  128. Giacomo Grasselli
  129. Gianni Pezzoli
  130. Giorgio Costantino
  131. Giovanni Albano
  132. Giulia Cardamone
  133. Giuseppe Bellelli
  134. Giuseppe Citerio
  135. Giuseppe Foti
  136. Giuseppe Lamorte
  137. Giuseppe Matullo
  138. Guido Baselli
  139. Hayato Kurihara
  140. Holger Neb
  141. Ilaria My
  142. Ingo Kurth
  143. Isabel Hernández
  144. Isabell Pink
  145. Itziar de Rojas
  146. Iván Galván-Femenia
  147. Jan Cato Holter
  148. Jan Egil Afset
  149. Jan Heyckendorf
  150. Jan Kässens
  151. Jan Kristian DamĂĄs
  152. Jan Rybniker
  153. Janine AltmĂĽller
  154. Javier Ampuero
  155. Javier MartĂ­n
  156. Jeanette Erdmann
  157. Jesus M Banales
  158. Joan Ramon Badia
  159. Joaquin Dopazo
  160. Jochen Schneider
  161. Jonas Bergan
  162. Jordi Barretina
  163. Jörn Walter
  164. Jose Hernández Quero
  165. Josune Goikoetxea
  166. Juan Delgado
  167. Juan M Guerrero
  168. Julia Fazaal
  169. Julia Kraft
  170. Julia Schröder
  171. Kari Risnes
  172. Karina Banasik
  173. Karl Erik MĂĽller
  174. Karoline I Gaede
  175. Koldo Garcia-Etxebarria
  176. Kristian Tonby
  177. Lars Heggelund
  178. Laura Izquierdo-Sanchez
  179. Laura Rachele Bettini
  180. Lauro Sumoy
  181. Leif Erik Sander
  182. Lena J Lippert
  183. Leonardo Terranova
  184. Lindokuhle Nkambule
  185. Lisa Knopp
  186. Lise Tuset Gustad
  187. Lucia Garbarino
  188. Luigi Santoro
  189. Luis TĂ©llez
  190. Luisa Roade
  191. Mahnoosh Ostadreza
  192. Maider Intxausti
  193. Manolis Kogevinas
  194. Mar Riveiro-Barciela
  195. Marc M Berger
  196. Marco Schaefer
  197. Mari EK Niemi
  198. María A Gutiérrez-Stampa
  199. Maria Carrabba
  200. Maria E. Figuera Basso
  201. Maria Grazia Valsecchi
  202. MarĂ­a Hernandez-Tejero
  203. Maria JGT Vehreschild
  204. Maria Manunta
  205. Marialbert Acosta-Herrera
  206. Mariella D’Angiò
  207. Marina Baldini
  208. Marina Cazzaniga
  209. Marit M Grimsrud
  210. Markus Cornberg
  211. Markus M Nöthen
  212. Marta Marquié
  213. Massimo Castoldi
  214. Mattia Cordioli
  215. Maurizio Cecconi
  216. Mauro D’Amato
  217. Max Augustin
  218. Melissa Tomasi
  219. Mercè Boada
  220. Michael Dreher
  221. Michael J Seilmaier
  222. Michael Joannidis
  223. Michael Wittig
  224. Michela Mazzocco
  225. Michele Ciccarelli
  226. Miguel RodrĂ­guez-GandĂ­a
  227. Monica Bocciolone
  228. Monica Miozzo
  229. Natale Imaz Ayo
  230. Natalia Blay
  231. Natalia Chueca
  232. Nicola Montano
  233. Nicole Braun
  234. Nicole Ludwig
  235. Nikolaus Marx
  236. Nilda MartĂ­nez
  237. Norwegian SARS-CoV-2 Study group
  238. Oliver A Cornely
  239. Oliver Witzke
  240. Orazio Palmieri
  241. Pa COVID-19 Study Group
  242. Paola Faverio
  243. Paoletta Preatoni
  244. Paolo Bonfanti
  245. Paolo Omodei
  246. Paolo Tentorio
  247. Pedro Castro
  248. Pedro M Rodrigues
  249. Pedro Pablo España
  250. Per Hoffmann
  251. Philip Rosenstiel
  252. Philipp Schommers
  253. Phillip Suwalski
  254. RaĂşl de Pablo
  255. Ricard Ferrer
  256. Robert Bals
  257. Roberta Gualtierotti
  258. Rocío Gallego-Durán
  259. Rosa Nieto
  260. Rossana Carpani
  261. Rubén Morilla
  262. Salvatore Badalamenti
  263. Sammra Haider
  264. Sandra Ciesek
  265. Sandra May
  266. Sara Bombace
  267. Sara Marsal
  268. Sara Pigazzini
  269. Sebastian Klein
  270. Serena Pelusi
  271. Sibylle Wilfling
  272. Silvano Bosari
  273. Sonja Volland
  274. Søren Brunak
  275. Soumya Raychaudhuri
  276. Stefan Schreiber
  277. Stefanie Heilmann-Heimbach
  278. Stefano Aliberti
  279. Stephan Ripke
  280. Susanne Dudman
  281. Tanja Wesse
  282. Tenghao Zheng
  283. The Humanitas COVID-19 Task Force
  284. The Humanitas Gavazzeni COVID-19 Task Force
  285. Thomas Bahmer
  286. Thomas Eggermann
  287. Thomas Illig
  288. Thorsten Brenner
  289. Tomas Pumarola
  290. Torsten Feldt
  291. Trine Folseraas
  292. Trinidad Gonzalez Cejudo
  293. Ulf Landmesser
  294. Ulrike Protzer
  295. Ute Hehr
  296. Valeria Rimoldi
  297. Valter Monzani
  298. Vegard Skogen
  299. Verena Keitel
  300. Verena Kopfnagel
  301. Vicente Friaza
  302. Victor Andrade
  303. Victor Moreno
  304. Wolfgang Albrecht
  305. Wolfgang Peter
  306. Wolfgang Poller
  307. Xavier Farre
  308. Xiaoli Yi
  309. Xiaomin Wang
  310. Yascha Khodamoradi
  311. Zehra Karadeniz
  312. Anna Latiano
  313. Siegfried Goerg
  314. Petra Bacher
  315. Philipp Koehler
  316. Florian Tran
  317. Heinz Zoller
  318. Eva C Schulte
  319. Bettina Heidecker
  320. Kerstin U Ludwig
  321. Javier Fernández
  322. Manuel Romero-GĂłmez
  323. AgustĂ­n Albillos
  324. Pietro Invernizzi
  325. Maria Buti
  326. Stefano Duga
  327. Luis Bujanda
  328. Johannes R Hov
  329. Tobias L Lenz
  330. Rosanna Asselta
  331. Rafael de Cid
  332. Luca Valenti
  333. Tom H Karlsen
  334. Mario Cáceres
  335. Andre Franke
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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 5threlease of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, includingNAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

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