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Novel genes and sex differences in COVID-19 severity.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Cruz R
  • Almeida SD
  • Heredia ML
  • Quintela I
  • Ceballos FC
  • Pita G
  • Lorenzo-Salazar JM
  • González-Montelongo R
  • Gago-Domínguez M
  • Porras MS
  • Castaño JAT
  • Nevado J
  • Aguado JM
  • Aguilar C
  • Aguilera-Albesa S
  • Almadana V
  • Almoguera B
  • Alvarez N
  • Andreu-Bernabeu Á
  • Arana-Arri E
  • Arango C
  • Arranz MJ
  • Artiga MJ
  • Baptista-Rosas RC
  • Barreda-Sánchez M
  • Belhassen-Garcia M
  • Bezerra JF
  • Bezerra MAC
  • Boix-Palop L
  • Brion M
  • Brugada R
  • Bustos M
  • Calderón EJ
  • Carbonell C
  • Castano L
  • Castelao JE
  • Conde-Vicente R
  • Cordero-Lorenzana ML
  • Cortes-Sanchez JL
  • Corton M
  • Darnaude MT
  • De Martino-Rodríguez A
  • Campo-Pérez V
  • Bustamante AD
  • Domínguez-Garrido E
  • Luchessi AD
  • Eiros R
  • Sanabria GME
  • Fariñas MC
  • Fernández-Robelo U
  • Fernández-Rodríguez A
  • Fernández-Villa T
  • Gil-Fournier B
  • Gómez-Arrue J
  • Álvarez BG
  • Quirós FGB
  • González-Peñas J
  • Gutiérrez-Bautista JF
  • Herrero-Gonzalez A
  • Jimenez-Sousa MA
  • Lattig MC
  • Borja AL
  • Lopez-Rodriguez R
  • Mancebo E
  • Martín-López C
  • Martín V
  • Martinez-Nieto O
  • Martinez-Lopez I
  • Martinez-Resendez MF
  • Martinez-Perez A
  • Mazzeu JF
  • Macías EM
  • Minguez P
  • Cuerda VM
  • Silbiger VN
  • Oliveira SF
  • Ortega-Paino E
  • Parellada M
  • Paz-Artal E
  • Santos NPC
  • Pérez-Matute P
  • Perez P
  • Pérez-Tomás ME
  • Perucho T
  • Pinsach-Abuin ML
  • Pompa-Mera EN
  • Porras-Hurtado GL
  • Pujol A
  • León SR
  • Resino S
  • Fernandes MR
  • Rodríguez-Ruiz E
  • Rodriguez-Artalejo F
  • Rodriguez-Garcia JA
  • Ruiz Cabello F
  • Ruiz-Hornillos J
  • Ryan P
  • Soria JM
  • Souto JC
  • Tamayo E
  • Tamayo-Velasco A
  • Taracido-Fernandez JC
  • Teper A
  • Torres-Tobar L
  • Urioste M
  • Valencia-Ramos J
  • Yáñez Z
  • Zarate R
  • Nakanishi T
  • Pigazzini S
  • Degenhardt F
  • Butler-Laporte G
  • Maya-Miles D
  • Bujanda L
  • Bouysran Y
  • Palom A
  • Ellinghaus D
  • Martínez-Bueno M
  • Rolker S
  • Amitrano S
  • Roade L
  • Fava F
  • Spinner CD
  • Prati D
  • Bernardo D
  • Garcia F
  • Darcis G
  • Fernández-Cadenas I
  • Holter JC
  • Banales JM
  • Frithiof R
  • Duga S
  • Asselta R
  • Pereira AC
  • Romero-Gómez M
  • Nafría-Jiménez B
  • Hov JR
  • Migeotte I
  • Renieri A
  • Planas AM
  • Ludwig KU
  • Buti M
  • Rahmouni S
  • Alarcón-Riquelme ME
  • Schulte EC
  • Franke A
  • Karlsen TH
  • Valenti L
  • Zeberg H
  • Richards B
  • Ganna A
  • Boada M
  • Rojas I
  • Ruiz A
  • Sánchez-Juan P
  • Real LM
  • SCOURGE Cohort Group
  • HOSTAGE Cohort Group
  • GRA@CE Cohort Group
  • Guillen-Navarro E
  • Ayuso C
  • González-Neira A
  • Riancho JA
  • Rojas-Martinez A
  • Flores C
  • Lapunzina P
  • Carracedo A

Grupos

Abstract

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or = 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

© The Author(s) 2022. Published by Oxford University Press.

Datos de la publicación

ISSN/ISSNe:
0964-6906, 1460-2083

HUMAN MOLECULAR GENETICS  OXFORD UNIV PRESS

Tipo:
Article
Páginas:
3789-3806
Factor de Impacto:
2,180 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 22

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Keywords

  • ANDROGEN RECEPTOR; AUTOZYGOSITY; HOMOZYGOSITY; ASSOCIATION; INTERFERON; COMPLEMENT; EXPRESSION; GENETICS; RANGE; LUNG

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