Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections1, 2. Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction3–5. The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative6, 7 to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity6, lung function8, and cancers9, suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.
Genome-wide Association Study of Long COVID / V. Lammi, T. Nakanishi, S.E. Jones, S.J. Andrews, J. Karjalainen, B. Cortés, H.E. O’Brien, B.E. Fulton-Howard, H.H. Haapaniemi, A. Schmidt, R.E. Mitchell, A. Mousas, M. Mangino, A. Huerta-Chagoya, N. Sinnott-Armstrong, E.T. Cirulli, M. Vaudel, A.S.F. Kwong, A.K. Maiti, M. Marttila, C. Batini, F. Minnai, A.R. Dearman, C.A.R. Warmerdam, C.B. Sequeros, T.W. Winkler, D.M. Jordan, L. Guare, E. Vergasova, E. Marouli, P. Striano, U.A. Zainulabid, A. Kumar, H.F. Ahmad, R. Edahiro, S. Azekawa, J.J. Grzymski, M. Ishii, Y. Okada, N.D. Beckmann, M. Kumari, R. Wagner, I.M. Heid, C. John, P.J. Short, P. Magnus, K. Banasik, F. Geller, L.H. Franke, A. Rakitko, E.L. Duncan, A. Renieri, K.K. Tsilidis, R. de Cid, A. Niavarani, T. Tusié-Luna, S.S. Verma, G.D. Smith, N.J. Timpson, M.J. Daly, A. Ganna, E.C. Schulte, J.B. Richards, K.U. Ludwig, M. Hultström, H. Zeberg, H.M. Ollila, N. Null, N. Null, N. Null, N. Null. - (2023 Jul 01). [10.1101/2023.06.29.23292056]
Genome-wide Association Study of Long COVID
F. Minnai;
2023
Abstract
Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections1, 2. Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction3–5. The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative6, 7 to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity6, lung function8, and cancers9, suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.
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