Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/44763
Title: Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
Authors: NAKANISHI, TomokoPIGAZZINI, SaraDEGENHARDT, FraukeCORDIOLI, MattiaBUTLER-LAPORTE, GuillaumeMAYA-MILES, DouglasBUJANDA, LuisBOUYSRAN, YoussefNIEMI, Mari E. K.PALOM, AdrianaELLINGHAUS, DavidKHAN, AtlasMARTINEZ-BUENO, ManuelROLKER, SelinaAMITRANO, SaraTATO, Luisa RoadeFAVA, FrancescaSPINNER, Christoph D.PRATI, DanieleBERNARDO, DavidGARCIA, FedericoDARCIS, GillesFERNANDEZ-CADENAS, IsraelHOLTER, Jan CatoBANALES, Jesus M.FRITHIOF, RobertKIRYLUK, KrzysztofDUGA, StefanoASSELTA, RosannaPEREIRA, Alexandre C.ROMERO-GOMEZ, ManuelNAFRIA-JIMENEZ, BeatrizHOV, Johannes R.MIGEOTTE, IsabelleRENIERI, AlessandraPLANAS, Anna M.LUDWIG, Kerstin U.BUTI, MariaRAHMOUNI, SouadALARCON-RIQUELME, Marta E.SCHULTE, Eva C.FRANKE, AndreKARLSEN, Tom H.VALENTI, LucaZEBERG, HugoRICHARDS, J. BrentGANNA, Andrea
Citation: JOURNAL OF CLINICAL INVESTIGATION, v.131, n.23, 2021
Abstract: BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
Appears in Collections:

Artigos e Materiais de Revistas Científicas - COVID-19
COVID-19

Artigos e Materiais de Revistas Científicas - HC/InCor
Instituto do Coração - HC/InCor

Artigos e Materiais de Revistas Científicas - LIM/13
LIM/13 - Laboratório de Genética e Cardiologia Molecular

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar


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