Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

التفاصيل البيبلوغرافية
العنوان:	Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
المؤلفون:	Matuozzo, D., Talouarn, E., Marchal, A., Zhang, P., Manry, J., Seeleuthner, Y., Zhang, Y., Bolze, A., Chaldebas, M., Milisavljevic, B., Gervais, A., Bastard, P., Asano, T., Bizien, L., Barzaghi, F., Abolhassani, H., Abou Tayoun, A., Aiuti, A., Alavi Darazam, I., Allende, L.M., Alonso-Arias, R., Arias, A.A., Aytekin, G., Bergman, P., Bondesan, S., Bryceson, Y.T., Bustos, I.G., Cabrera-Marante, O., Carcel, S., Carrera, P., Casari, G., Chaïbi, K., Colobran, R., Condino-Neto, A., Covill, L.E., Delmonte, O.M., El Zein, L., Flores, C., Gregersen, P.K., Gut, M., Haerynck, F., Halwani, R., Hancerli, S., Hammarström, L., Hatipoğlu, N., Karbuz, A., Keles, S., Kyheng, C., Leon-Lopez, R., Franco, J.L., Mansouri, D., Martinez-Picado, J., Metin Akcan, O., Migeotte, I., Morange, P.E., Morelle, G., Martin-Nalda, A., Novelli, G., Novelli, A., Ozcelik, T., Palabiyik, F., Pan-Hammarström, Q., de Diego, R.P., Planas-Serra, L., Pleguezuelo, D.E., Prando, C., Pujol, A., Reyes, L.F., Rivière, J.G., Rodriguez-Gallego, C., Rojas, J., Rovere-Querini, P., Schlüter, A., Shahrooei, M., Sobh, A., Soler-Palacin, P., Tandjaoui-Lambiotte, Y., Tipu, I., Tresoldi, C., Troya, J., van de Beek, D., Zatz, M., Zawadzki, P., Al-Muhsen, S.Z., Alosaimi, M.F., Alsohime, F.M., Baris-Feldman, H., Butte, M.J., Constantinescu, S.N., Cooper, M.A., Dalgard, C.L., Fellay, J., Heath, J.R., Lau, Y.L., Lifton, R.P., Maniatis, T., Mogensen, T.H., von Bernuth, H., Lermine, A., Vidaud, M., Boland, A., Deleuze, J.F., Nussbaum, R., Kahn-Kirby, A., Mentre, F., Tubiana, S., Gorochov, G., Tubach, F., Hausfater, P., Meyts, I., Zhang, S.Y., Puel, A., Notarangelo, L.D., Boisson-Dupuis, S., Su, H.C., Boisson, B., Jouanguy, E., Casanova, J.L., Zhang, Q., Abel, L., Cobat, A.
المساهمون:	COVID Human Genetic Effort, COVIDeF Study Group, French COVID Cohort Study Group, CoV-Contact Cohort, COVID-STORM Clinicians, COVID Clinicians, Orchestra Working Group, Amsterdam UMC Covid-19 Biobank, NIAID-USUHS COVID Study Group, Abel, L., Al-Muhsen, S., Al-Mulla, F., Anderson, M.S., Andreakos, E., Arias, A.A., Feldman, H.B., Belot, A., Biggs, C.M., Bogunovic, D., Bondarenko, A., Bousfiha, A.A., Brodin, P., Bryceson, Y., Bustamante, C.D., Chakravorty, S., Christodoulou, J., Desai, M., Drolet, B.A., Baghdadi, J.E., Espinosa-Padilla, S., Franco, J.L., Froidure, A., Hagin, D., Henrickson, S.E., Hsieh, EWY, Husebye, E., Imai, K., Itan, Y., Jarvis, E.D., Karamitros, T., Kisand, K., Ku, C.L., Ling, Y., Lucas, C.L., Maródi, L., Meyts, I., Milner, J.D., Mironska, K., Morio, T., Ng, LFP, Notarangelo, L.D., O'Farrelly, C., Okada, S., Planas, A.M., Quintana-Murci, L., Renia, L., Resnick, I., Rodríguez-Gallego, C., Sancho-Shimizu, V., Sediva, A., Seppänen, MRJ, Shcherbina, A., Slaby, O., Snow, A.L., Soler-Palacín, P., Spaan, A.N., Tancevski, I., Tangye, S.G., Ramaswamy, S., Turvey, S.E., Uddin, F., Uddin, M.J., van de Beek, D., Vinh, D.C., Zatz, M., Su, H.C., Casanova, J.L., Bureau, S., Vacher, Y., Gysembergh-Houal, A., Demerville, L., Chachoua, A., Abad, S., Abassi, R., Abdellaoui, A., Abdelmalek, A., Abdoul, H., Abergel, H., Abeud, F., Abgrall, S., Abisror, N., Adechian, M., Aderdour, N., Admane, H.F., Adnet, F., Afritt, S., Agostini, H., Aguilar, C., Agut, S., Aiello, T.F.
المصدر:	Genome medicine, vol. 15, no. 1, pp. 22
سنة النشر:	2023
المجموعة:	Université de Lausanne (UNIL): Serval - Serveur académique lausannois
مصطلحات موضوعية:	Humans, Young Adult, Adult, Middle Aged, COVID-19, SARS-CoV-2, Toll-Like Receptor 3/genetics, Toll-Like Receptor 7, Interferon Type I, Autoantibodies, Immunity, Rare variants, Type I interferon
الوصف:	We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10 -4 ) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10 -4 ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10 -3 ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10 -8 ). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10 -5 ). Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
نوع الوثيقة:	article in journal/newspaper
اللغة:	English
تدمد:	1756-994X
العلاقة:	info:eu-repo/semantics/altIdentifier/pmid/37020259; info:eu-repo/semantics/altIdentifier/eissn/1756-994X; https://serval.unil.ch/notice/serval:BIB_31798B2B6490Test; urn:issn:1756-994X
DOI:	10.1186/s13073-023-01173-8
الإتاحة:	https://doi.org/10.1186/s13073-023-01173-8Test https://serval.unil.ch/notice/serval:BIB_31798B2B6490Test
رقم الانضمام:	edsbas.332D99E2
قاعدة البيانات:	BASE

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الوصف
تدمد:	1756994X
DOI:	10.1186/s13073-023-01173-8