Colocalization of expression transcripts with COVID-19 outcomes is rare across cell states, cell types and organs.
Journal
Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
16
10
2022
accepted:
30
06
2023
medline:
21
9
2023
pubmed:
29
8
2023
entrez:
28
8
2023
Statut:
ppublish
Résumé
Identifying causal genes at GWAS loci can help pinpoint targets for therapeutic interventions. Expression studies can disentangle such loci but signals from expression quantitative trait loci (eQTLs) often fail to colocalize-which means that the genetic control of measured expression is not shared with the genetic control of disease risk. This may be because gene expression is measured in the wrong cell type, physiological state, or organ. We tested whether Mendelian randomization (MR) could identify genes at loci influencing COVID-19 outcomes and whether the colocalization of genetic control of expression and COVID-19 outcomes was influenced by cell type, cell stimulation, and organ. We conducted MR of cis-eQTLs from single cell (scRNA-seq) and bulk RNA sequencing. We then tested variables that could influence colocalization, including cell type, cell stimulation, RNA sequencing modality, organ, symptoms of COVID-19, and SARS-CoV-2 status among individuals with symptoms of COVID-19. The outcomes used to test colocalization were COVID-19 severity and susceptibility as assessed in the Host Genetics Initiative release 7. Most transcripts identified using MR did not colocalize when tested across cell types, cell state and in different organs. Most that did colocalize likely represented false positives due to linkage disequilibrium. In general, colocalization was highly variable and at times inconsistent for the same transcript across cell type, cell stimulation and organ. While we identified factors that influenced colocalization for select transcripts, identifying 33 that mediate COVID-19 outcomes, our study suggests that colocalization of expression with COVID-19 outcomes is partially due to noisy signals even after following quality control and sensitivity testing. These findings illustrate the present difficulty of linking expression transcripts to disease outcomes and the need for skepticism when observing eQTL MR results, even accounting for cell types, stimulation state and different organs.
Identifiants
pubmed: 37640912
doi: 10.1007/s00439-023-02590-w
pii: 10.1007/s00439-023-02590-w
pmc: PMC10511363
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1461-1476Subventions
Organisme : CIHR
ID : CIHR: 365825; 409511
Pays : Canada
Organisme : CIHR
ID : 100558
Pays : Canada
Organisme : CIHR
ID : 169303
Pays : Canada
Organisme : CIHR
ID : 476575
Pays : Canada
Organisme : CIHR
ID : CIHR: 365825; 409511
Pays : Canada
Organisme : CIHR
ID : 100558
Pays : Canada
Organisme : CIHR
ID : 169303
Pays : Canada
Organisme : CIHR
ID : 476575
Pays : Canada
Informations de copyright
© 2023. The Author(s).
Références
Baranova A, Cao H, Zhang F (2021) Unraveling risk genes of COVID-19 by multi-omics integrative analyses. Front Med (lausanne). 8:738687. https://doi.org/10.3389/fmed.2021.738687
doi: 10.3389/fmed.2021.738687
pubmed: 34557504
pmcid: 8452849
Baranova A, Cao H, Chen J, Zhang F (2022a) Causal association and shared genetics between asthma and COVID-19. Front Immunol 13:705379. https://doi.org/10.3389/fimmu.2022.705379
doi: 10.3389/fimmu.2022.705379
pubmed: 35386719
pmcid: 8977836
Baranova A, Cao H, Zhang F (2022b) Severe COVID-19 increases the risk of schizophrenia. Psychiatry Res 317:114809. https://doi.org/10.1016/j.psychres.2022.114809
doi: 10.1016/j.psychres.2022.114809
pubmed: 36037742
pmcid: 9398553
Baranova A, Cao H, Teng S, Zhang F (2023) A phenome-wide investigation of risk factors for severe COVID-19. J Med Virol 95:e28264. https://doi.org/10.1002/jmv.28264
doi: 10.1002/jmv.28264
pubmed: 36316288
Connally NJ, Nazeen S, Lee D, Shi H, Stamatoyannopoulos J, Chun S, Cotsapas C, Cassa CA, Sunyaev SR (2022) The missing link between genetic association and regulatory function. Elife. https://doi.org/10.7554/eLife.74970
doi: 10.7554/eLife.74970
pubmed: 36515579
pmcid: 9842386
Covid-19 Host Genetics Initiative (2021) Mapping the human genetic architecture of COVID-19. Nature 600:472–477. https://doi.org/10.1038/s41586-021-03767-x
doi: 10.1038/s41586-021-03767-x
Covid-19 Host Genetics Initiative (2022) A first update on mapping the human genetic architecture of COVID-19. Nature 608:E1–E10. https://doi.org/10.1038/s41586-022-04826-7
doi: 10.1038/s41586-022-04826-7
D’Antonio M, Nguyen JP, Arthur TD, Matsui H, Initiative C-HG, D’Antonio-Chronowska A, Frazer KA (2021) SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues. Cell Rep 37:110020. https://doi.org/10.1016/j.celrep.2021.110020
doi: 10.1016/j.celrep.2021.110020
pubmed: 34762851
pmcid: 8563343
Davies NM, Holmes MV, Davey Smith G (2018) Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ 362:k601. https://doi.org/10.1136/bmj.k601
doi: 10.1136/bmj.k601
pubmed: 30002074
pmcid: 6041728
De Biasi S, Meschiari M, Gibellini L, Bellinazzi C, Borella R, Fidanza L, Gozzi L, Iannone A, Lo Tartaro D, Mattioli M, Paolini A, Menozzi M, Milic J, Franceschi G, Fantini R, Tonelli R, Sita M, Sarti M, Trenti T, Brugioni L, Cicchetti L, Facchinetti F, Pietrangelo A, Clini E, Girardis M, Guaraldi G, Mussini C, Cossarizza A (2020) Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia. Nat Commun 11:3434. https://doi.org/10.1038/s41467-020-17292-4
doi: 10.1038/s41467-020-17292-4
pubmed: 32632085
pmcid: 7338513
Degenhardt F, Ellinghaus D, Juzenas S, Lerga-Jaso J, Wendorff M, Maya-Miles D, Uellendahl-Werth F, ElAbd H, Ruhlemann MC, Arora J, Ozer O, Lenning OB, Myhre R, Vadla MS, Wacker EM, Wienbrandt L, Blandino Ortiz A, de Salazar A, Garrido Chercoles A, Palom A, Ruiz A, Garcia-Fernandez AE, Blanco-Grau A, Mantovani A, Zanella A, Holten AR, Mayer A, Bandera A, Cherubini A, Protti A, Aghemo A, Gerussi A, Ramirez A, Braun A, Nebel A, Barreira A, Lleo A, Teles A, Kildal AB, Biondi A, Caballero-Garralda A, Ganna A, Gori A, Gluck A, Lind A, Tanck A, Hinney A, Carreras Nolla A, Fracanzani AL, Peschuck A, Cavallero A, Dyrhol-Riise AM, Ruello A, Julia A, Muscatello A, Pesenti A, Voza A, Rando-Segura A, Solier A, Schmidt A, Cortes B, Mateos B, Nafria-Jimenez B, Schaefer B, Jensen B, Bellinghausen C, Maj C, Ferrando C, de la Horra C, Quereda C, Skurk C, Thibeault C, Scollo C, Herr C, Spinner CD, Gassner C, Lange C, Hu C, Paccapelo C, Lehmann C, Angelini C, Cappadona C, Azuure C, Bianco C, Cea C, Sancho C, Hoff DAL, Galimberti D, Prati D, Haschka D, Jimenez D, Pestana D, Toapanta D, Muniz-Diaz E, Azzolini E, Sandoval E, Binatti E, Scarpini E, Helbig ET et al (2022) Detailed stratified GWAS analysis for severe COVID-19 in four European populations. Hum Mol Genet 31:3945–3966. https://doi.org/10.1093/hmg/ddac158
doi: 10.1093/hmg/ddac158
pubmed: 35848942
pmcid: 9703941
Forgetta V, Jiang L, Vulpescu NA, Hogan MS, Chen S, Morris JA, Grinek S, Benner C, Jang DK, Hoang Q, Burtt N, Flannick JA, McCarthy MI, Fauman E, Greenwood CMT, Maurano MT, Richards JB (2022) An effector index to predict target genes at GWAS loci. Hum Genet. https://doi.org/10.1007/s00439-022-02434-z
doi: 10.1007/s00439-022-02434-z
pubmed: 35147782
Fricke-Galindo I, Martinez-Morales A, Chavez-Galan L, Ocana-Guzman R, Buendia-Roldan I, Perez-Rubio G, Hernandez-Zenteno RJ, Veronica-Aguilar A, Alarcon-Dionet A, Aguilar-Duran H, Gutierrez-Perez IA, Zaragoza-Garcia O, Alanis-Ponce J, Camarena A, Bautista-Becerril B, Nava-Quiroz KJ, Mejia M, Guzman-Guzman IP, Falfan-Valencia R (2022) IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19. Front Immunol 13:949413. https://doi.org/10.3389/fimmu.2022.949413
doi: 10.3389/fimmu.2022.949413
pubmed: 35967349
pmcid: 9374460
Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, Ho YL, Iyengar SK, Kosik NM, Vujkovic M, Gagnon DR, Bento AP, Barrio-Hernandez I, Ronnblom L, Hagberg N, Lundtoft C, Langenberg C, Pietzner M, Valentine D, Gustincich S, Tartaglia GG, Allara E, Surendran P, Burgess S, Zhao JH, Peters JE, Prins BP, Angelantonio ED, Devineni P, Shi Y, Lynch KE, DuVall SL, Garcon H, Thomann LO, Zhou JJ, Gorman BR, Huffman JE, O’Donnell CJ, Tsao PS, Beckham JC, Pyarajan S, Muralidhar S, Huang GD, Ramoni R, Beltrao P, Danesh J, Hung AM, Chang KM, Sun YV, Joseph J, Leach AR, Edwards TL, Cho K, Gaziano JM, Butterworth AS, Casas JP, Initiative VAMVPC-S (2021) Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19. Nat Med 27:668–676. https://doi.org/10.1038/s41591-021-01310-z
doi: 10.1038/s41591-021-01310-z
pubmed: 33837377
pmcid: 7612986
GTEx Consortium (2020) The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369:1318–1330. https://doi.org/10.1126/science.aaz1776
doi: 10.1126/science.aaz1776
Hernandez Cordero AI, Li X, Milne S, Yang CX, Bosse Y, Joubert P, Timens W, van den Berge M, Nickle D, Hao K, Sin DD (2021) Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19. Hum Genet 140:969–979. https://doi.org/10.1007/s00439-021-02264-5
doi: 10.1007/s00439-021-02264-5
pubmed: 33604698
pmcid: 7892327
Kanai M, Ulirsch JC, Karjalainen J, Kurki M, Karczewski KJ, Fauman E, Wang QS, Jacobs H, Aguet F, Ardlie KG, Kerimov N, Alasoo K, Benner C, Ishigaki K, Sakaue S, Reilly S, Kamatani Y, Matsuda K, Palotie A, Neale BM, Tewhey R, Sabeti PC, Okada Y, Daly MJ, Finucane HK (2021) Insights from complex trait fine-mapping across diverse populations. MedRxiv. https://doi.org/10.1101/2021.09.03.21262975
doi: 10.1101/2021.09.03.21262975
Kanai M, Elzur R, Zhou W, Global Biobank Meta-analysis I, Daly MJ, Finucane HK (2022) Meta-analysis fine-mapping is often miscalibrated at single-variant resolution. Cell Genom. https://doi.org/10.1016/j.xgen.2022.100210
doi: 10.1016/j.xgen.2022.100210
pubmed: 36778051
pmcid: 9903716
Kousathanas A, Pairo-Castineira E, Rawlik K, Stuckey A, Odhams CA, Walker S, Russell CD, Malinauskas T, Wu Y, Millar J, Shen X, Elliott KS, Griffiths F, Oosthuyzen W, Morrice K, Keating S, Wang B, Rhodes D, Klaric L, Zechner M, Parkinson N, Siddiq A, Goddard P, Donovan S, Maslove D, Nichol A, Semple MG, Zainy T, Maleady-Crowe F, Todd L, Salehi S, Knight J, Elgar G, Chan G, Arumugam P, Patch C, Rendon A, Bentley D, Kingsley C, Kosmicki JA, Horowitz JE, Baras A, Abecasis GR, Ferreira MAR, Justice A, Mirshahi T, Oetjens M, Rader DJ, Ritchie MD, Verma A, Fowler TA, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Elliott P, Walsh T, Tenesa A, Oi G, Me I, Initiative C-HG, Fawkes A, Murphy L, Rowan K, Ponting CP, Vitart V, Wilson JF, Yang J, Bretherick AD, Scott RH, Hendry SC, Moutsianas L, Law A, Caulfield MJ, Baillie JK (2022) Whole-genome sequencing reveals host factors underlying critical COVID-19. Nature 607:97–103. https://doi.org/10.1038/s41586-022-04576-6
doi: 10.1038/s41586-022-04576-6
pubmed: 35255492
pmcid: 9259496
Krishnamoorthy S, Li GH, Cheung CL (2023) Transcriptome-wide summary data-based Mendelian randomization analysis reveals 38 novel genes associated with severe COVID-19. J Med Virol 95:e28162. https://doi.org/10.1002/jmv.28162
doi: 10.1002/jmv.28162
pubmed: 36127160
Kundu R, Narean JS, Wang L, Fenn J, Pillay T, Fernandez ND, Conibear E, Koycheva A, Davies M, Tolosa-Wright M, Hakki S, Varro R, McDermott E, Hammett S, Cutajar J, Thwaites RS, Parker E, Rosadas C, McClure M, Tedder R, Taylor GP, Dunning J, Lalvani A (2022) Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts. Nat Commun 13:80. https://doi.org/10.1038/s41467-021-27674-x
doi: 10.1038/s41467-021-27674-x
pubmed: 35013199
pmcid: 8748880
Lamontagne M, Berube JC, Obeidat M, Cho MH, Hobbs BD, Sakornsakolpat P, de Jong K, Boezen HM, Nickle D, Hao K, Timens W, van den Berge M, Joubert P, Laviolette M, Sin DD, Pare PD, Bosse Y, International CGC (2018) Leveraging lung tissue transcriptome to uncover candidate causal genes in COPD genetic associations. Hum Mol Genet 27:1819–1829. https://doi.org/10.1093/hmg/ddy091
doi: 10.1093/hmg/ddy091
pubmed: 29547942
pmcid: 5932553
Li P, Ke Y, Shen W, Shi S, Wang Y, Lin K, Guo X, Wang C, Zhang Y, Zhao Z (2022) Targeted screening of genetic associations with COVID-19 susceptibility and severity. Front Genet 13:1073880. https://doi.org/10.3389/fgene.2022.1073880
doi: 10.3389/fgene.2022.1073880
pubmed: 36531218
pmcid: 9747945
Liu D, Yang J, Feng B, Lu W, Zhao C, Li L (2021) Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19. J Infect 82:126–132. https://doi.org/10.1016/j.jinf.2020.11.031
doi: 10.1016/j.jinf.2020.11.031
pubmed: 33259846
Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, Alanio C, Kuri-Cervantes L, Pampena MB, D’Andrea K, Manne S, Chen Z, Huang YJ, Reilly JP, Weisman AR, Ittner CAG, Kuthuru O, Dougherty J, Nzingha K, Han N, Kim J, Pattekar A, Goodwin EC, Anderson EM, Weirick ME, Gouma S, Arevalo CP, Bolton MJ, Chen F, Lacey SF, Ramage H, Cherry S, Hensley SE, Apostolidis SA, Huang AC, Vella LA, Unit UPCP, Betts MR, Meyer NJ, Wherry EJ (2020) Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. https://doi.org/10.1126/science.abc8511
doi: 10.1126/science.abc8511
pubmed: 32669297
pmcid: 7402624
Mehandru S, Merad M (2022) Pathological sequelae of long-haul COVID. Nat Immunol 23:194–202. https://doi.org/10.1038/s41590-021-01104-y
doi: 10.1038/s41590-021-01104-y
pubmed: 35105985
pmcid: 9127978
Merad M, Blish CA, Sallusto F, Iwasaki A (2022) The immunology and immunopathology of COVID-19. Science 375:1122–1127. https://doi.org/10.1126/science.abm8108
doi: 10.1126/science.abm8108
pubmed: 35271343
Nakanishi T, Farjoun Y, Willett J, Allen RJ, Guillen-Guio B, Zhou S, Richards JB (2022) Alternative splicing in the lung influences COVID-19 severity and respiratory diseases. MedRxiv. https://doi.org/10.1101/2022.10.18.22281202
doi: 10.1101/2022.10.18.22281202
Ong EZ, Chan YFZ, Leong WY, Lee NMY, Kalimuddin S, Haja Mohideen SM, Chan KS, Tan AT, Bertoletti A, Ooi EE, Low JGH (2020) A dynamic immune response shapes COVID-19 progression. Cell Host Microbe 27:879–882. https://doi.org/10.1016/j.chom.2020.03.021
doi: 10.1016/j.chom.2020.03.021
pubmed: 32359396
pmcid: 7192089
Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, Walker S, Parkinson N, Fourman MH, Russell CD, Furniss J, Richmond A, Gountouna E, Wrobel N, Harrison D, Wang B, Wu Y, Meynert A, Griffiths F, Oosthuyzen W, Kousathanas A, Moutsianas L, Yang Z, Zhai R, Zheng C, Grimes G, Beale R, Millar J, Shih B, Keating S, Zechner M, Haley C, Porteous DJ, Hayward C, Yang J, Knight J, Summers C, Shankar-Hari M, Klenerman P, Turtle L, Ho A, Moore SC, Hinds C, Horby P, Nichol A, Maslove D, Ling L, McAuley D, Montgomery H, Walsh T, Pereira AC, Renieri A, Gen OI, Investigators IC, Initiative C-HG, Me I, Gen CI, Shen X, Ponting CP, Fawkes A, Tenesa A, Caulfield M, Scott R, Rowan K, Murphy L, Openshaw PJM, Semple MG, Law A, Vitart V, Wilson JF, Baillie JK (2021) Genetic mechanisms of critical illness in COVID-19. Nature 591:92–98. https://doi.org/10.1038/s41586-020-03065-y
doi: 10.1038/s41586-020-03065-y
pubmed: 33307546
Pairo-Castineira E, Rawlik K, Klaric L, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Stuckey A, Odhams CA, Walker S, Griffiths F, Oosthuyzen W, Morrice K, Keating S, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Walsh T, Tenesa A, Scott RH, Caulfield MJ, Moutsianas L, Ponting CP, Wilson JF, Vitart V, Pereira AC, Luchessi A, Parra E, Cruz-Guerrero R, Carracedo A, Fawkes A, Murphy L, Rowan K, Law A, Hendry SC, Baillie JK (2022) GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19. MedRxiv. https://doi.org/10.1101/2022.03.07.22271833
doi: 10.1101/2022.03.07.22271833
Pietzner M, Chua RL, Wheeler E, Jechow K, Willett JDS, Radbruch H, Trump S, Heidecker B, Zeberg H, Heppner FL, Eils R, Mall MA, Richards JB, Sander LE, Lehmann I, Lukassen S, Wareham NJ, Conrad C, Langenberg C (2022) ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19. Nat Commun 13:4484. https://doi.org/10.1038/s41467-022-31999-6
doi: 10.1038/s41467-022-31999-6
pubmed: 35970849
pmcid: 9378714
Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336–2337. https://doi.org/10.1093/bioinformatics/btq419
doi: 10.1093/bioinformatics/btq419
pubmed: 20634204
pmcid: 2935401
Randolph HE, Fiege JK, Thielen BK, Mickelson CK, Shiratori M, Barroso-Batista J, Langlois RA, Barreiro LB (2021) Genetic ancestry effects on the response to viral infection are pervasive but cell type specific. Science 374:1127–1133. https://doi.org/10.1126/science.abg0928
doi: 10.1126/science.abg0928
pubmed: 34822289
pmcid: 8957271
Rocheleau G, Forrest IS, Duffy A, Bafna S, Dobbyn A, Verbanck M, Won HH, Jordan DM, Do R (2022) A tissue-level phenome-wide network map of colocalized genes and phenotypes in the UK Biobank. Commun Biol 5:849. https://doi.org/10.1038/s42003-022-03820-z
doi: 10.1038/s42003-022-03820-z
pubmed: 35987940
pmcid: 9392744
Schmiedel BJ, Rocha J, Gonzalez-Colin C, Bhattacharyya S, Madrigal A, Ottensmeier CH, Ay F, Chandra V, Vijayanand P (2021) COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types. Nat Commun 12:6760. https://doi.org/10.1038/s41467-021-26888-3
doi: 10.1038/s41467-021-26888-3
pubmed: 34799557
pmcid: 8604964
Severe Covid GG, Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernandez J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kassens J, May S, Wendorff M, Wienbrandt L, Uellendahl-Werth F, Zheng T, Yi X, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julia A, Pesenti A, Voza A, Jimenez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestana D, Muniz-Diaz E, Sandoval E, Paraboschi EM, Navas E, Garcia Sanchez F, Ceriotti F, Martinelli-Boneschi F, Peyvandi F, Blasi F, Tellez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galvan-Femenia I, Martin J, Erdmann J, Ferrusquia-Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Ruhlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta-Herrera M, D’Angio M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M et al (2020) Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med 383:1522–1534. https://doi.org/10.1056/NEJMoa2020283
doi: 10.1056/NEJMoa2020283
Sharif-Zak M, Abbasi-Jorjandi M, Asadikaram G, Ghoreshi ZA, Rezazadeh-Jabalbarzi M, Afsharipur A, Rashidinejad H, Khajepour F, Jafarzadeh A, Arefinia N, Kheyrkhah A, Abolhassani M (2022) CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender. Immunobiology 227:152184. https://doi.org/10.1016/j.imbio.2022.152184
doi: 10.1016/j.imbio.2022.152184
pubmed: 35131543
pmcid: 8806394
Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, VanderWeele TJ, Higgins JPT, Timpson NJ, Dimou N, Langenberg C, Golub RM, Loder EW, Gallo V, Tybjaerg-Hansen A, Davey Smith G, Egger M, Richards JB (2021) Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement. JAMA 326:1614–1621. https://doi.org/10.1001/jama.2021.18236
doi: 10.1001/jama.2021.18236
pubmed: 34698778
Smith GD, Ebrahim S (2003) “Mendelian randomization”: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 32:1–22. https://doi.org/10.1093/ije/dyg070
doi: 10.1093/ije/dyg070
pubmed: 12689998
Soskic B, Cano-Gamez E, Smyth DJ, Ambridge K, Ke Z, Matte JC, Bossini-Castillo L, Kaplanis J, Ramirez-Navarro L, Lorenc A, Nakic N, Esparza-Gordillo J, Rowan W, Wille D, Tough DF, Bronson PG, Trynka G (2022) Immune disease risk variants regulate gene expression dynamics during CD4(+) T cell activation. Nat Genet. https://doi.org/10.1038/s41588-022-01066-3
doi: 10.1038/s41588-022-01066-3
pubmed: 35618845
pmcid: 9197762
Tan LY, Komarasamy TV, Rmt Balasubramaniam V (2021) Hyperinflammatory immune response and COVID-19: A double edged sword. Front Immunol 12:742941. https://doi.org/10.3389/fimmu.2021.742941
doi: 10.3389/fimmu.2021.742941
pubmed: 34659238
pmcid: 8515020
Wang L, Balmat TJ, Antonia AL, Constantine FJ, Henao R, Burke TW, Ingham A, McClain MT, Tsalik EL, Ko ER, Ginsburg GS, DeLong MR, Shen X, Woods CW, Hauser ER, Ko DC (2021) An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility. Genome Med 13:83. https://doi.org/10.1186/s13073-021-00904-z
doi: 10.1186/s13073-021-00904-z
pubmed: 34001247
pmcid: 8127495
Wang Y, Guga S, Wu K, Khaw Z, Tzoumkas K, Tombleson P, Comeau ME, Langefeld CD, Cunninghame Graham DS, Morris DL, Vyse TJ (2022) COVID-19 and systemic lupus erythematosus genetics: A balance between autoimmune disease risk and protection against infection. PLoS Genet 18:e1010253. https://doi.org/10.1371/journal.pgen.1010253
doi: 10.1371/journal.pgen.1010253
pubmed: 36327221
pmcid: 9632821
Wu L, Zhu J, Liu D, Sun Y, Wu C (2021) An integrative multiomics analysis identifies putative causal genes for COVID-19 severity. Genet Med 23:2076–2086. https://doi.org/10.1038/s41436-021-01243-5
doi: 10.1038/s41436-021-01243-5
pubmed: 34183789
pmcid: 8237048
Yoshiji S, Butler-Laporte G, Lu T, Willett JDS, Su CY, Nakanishi T, Morrison DR, Chen Y, Liang K, Hultstrom M, Ilboudo Y, Afrasiabi Z, Lan S, Duggan N, DeLuca C, Vaezi M, Tselios C, Xue X, Bouab M, Shi F, Laurent L, Munter HM, Afilalo M, Afilalo J, Mooser V, Timpson NJ, Zeberg H, Zhou S, Forgetta V, Farjoun Y, Richards JB (2023) Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity. Nat Metab 5:248–264. https://doi.org/10.1038/s42255-023-00742-w
doi: 10.1038/s42255-023-00742-w
pubmed: 36805566
pmcid: 9940690
Zheng J, Haberland V, Baird D, Walker V, Haycock PC, Hurle MR, Gutteridge A, Erola P, Liu Y, Luo S, Robinson J, Richardson TG, Staley JR, Elsworth B, Burgess S, Sun BB, Danesh J, Runz H, Maranville JC, Martin HM, Yarmolinsky J, Laurin C, Holmes MV, Liu JZ, Estrada K, Santos R, McCarthy L, Waterworth D, Nelson MR, Smith GD, Butterworth AS, Hemani G, Scott RA, Gaunt TR (2020) Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases. Nat Genet 52:1122–1131. https://doi.org/10.1038/s41588-020-0682-6
doi: 10.1038/s41588-020-0682-6
pubmed: 32895551
pmcid: 7610464
Zhou S, Butler-Laporte G, Nakanishi T, Morrison DR, Afilalo J, Afilalo M, Laurent L, Pietzner M, Kerrison N, Zhao K, Brunet-Ratnasingham E, Henry D, Kimchi N, Afrasiabi Z, Rezk N, Bouab M, Petitjean L, Guzman C, Xue X, Tselios C, Vulesevic B, Adeleye O, Abdullah T, Almamlouk N, Chen Y, Chasse M, Durand M, Paterson C, Normark J, Frithiof R, Lipcsey M, Hultstrom M, Greenwood CMT, Zeberg H, Langenberg C, Thysell E, Pollak M, Mooser V, Forgetta V, Kaufmann DE, Richards JB (2021) A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity. Nat Med 27:659–667. https://doi.org/10.1038/s41591-021-01281-1
doi: 10.1038/s41591-021-01281-1
pubmed: 33633408