A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality

被引：16

作者：

Verma, Anurag ^{[1
,2
]}

Minnier, Jessica ^{[4
,5
,6
]}

Wan, Emily S. ^{[7
,12
]}

Huffman, Jennifer E. ^{[8
]}

Gao, Lina ^{[5
,6
]}

Joseph, Jacob ^{[9
,13
]}

Ho, Yuk-Lam ^{[8
]}

Wu, Wen-Chih ^{[16
,17
,18
]}

Cho, Kelly ^{[8
,14
]}

Gorman, Bryan R. ^{[8
]}

Rajeevan, Nallakkandi ^{[19
,22
]}

Pyarajan, Saiju ^{[8
,15
]}

Garcon, Helene ^{[8
]}

Meigs, James B. ^{[24
]}

Sun, Yan V. ^{[26
,28
]}

Reaven, Peter D. ^{[29
,30
]}

McGeary, John E. ^{[31
,32
]}

Suzuki, Ayako ^{[33
,34
]}

Gelernter, Joel ^{[20
,23
]}

Lynch, Julie A. ^{[35
,36
]}

Petersen, Jeffrey M. ^{[1
,3
]}

Zekavat, Seyedeh Maryam ^{[21
,38
]}

Natarajan, Pradeep ^{[15
,25
,38
]}

Dalal, Sharvari ^{[1
,3
]}

Jhala, Darshana N. ^{[1
,3
]}

Arjomandi, Mehrdad ^{[39
]}

Gatsby, Elise ^{[35
]}

Lynch, Kristine E. ^{[35
,37
]}

Bonomo, Robert A. ^{[40
]}

Freiberg, Matthew ^{[42
]}

Pathak, Gita A. ^{[20
,23
]}

Zhou, Jin J. ^{[45
,46
]}

Donskey, Curtis J. ^{[47
]}

Madduri, Ravi K. ^{[49
]}

Wells, Quinn S. ^{[42
,43
,44
]}

Huang, Rose D. L. ^{[8
]}

Polimanti, Renato ^{[20
,23
]}

Chang, Kyong-Mi ^{[1
]}

Liao, Katherine P. ^{[10
]}

Tsao, Philip S. ^{[50
]}

Wilson, Peter W. F. ^{[27
,28
]}

Hung, Adriana M. ^{[51
]}

O'Donnell, Christopher J. ^{[11
]}

Gaziano, John M. ^{[8
]}

Hauger, Richard L. ^{[52
,53
]}

Iyengar, Sudha K. ^{[41
,48
]}

Luoh, Shiuh-Wen ^{[5
,6
]}

机构：

[1] Corporal Michael J Crescenz VA Med Ctr, Philadelphia, PA USA

[2] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] Oregon Hlth & Sci Univ, Portland, OR USA

[5] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA

[6] VA Portland Hlth Care Syst, Portland, OR USA

[7] VA Boston Healthcare Syst, Dept Med, Pulm Crit Care Sleep & Allergy Sect, Boston, MA USA

[8] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA

[9] VA Boston Healthcare Syst, Dept Med, Boston, MA USA

[10] VA Boston Healthcare Syst, Med, Rheumatol, Boston, MA USA

[11] VA Boston Healthcare Syst, Med, Cardiol, Boston, MA USA

[12] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[13] Brigham & Womens Hosp, Med, Cardiovasc, 75 Francis St, Boston, MA 02115 USA

[14] Brigham & Womens Hosp, Med, Aging, 75 Francis St, Boston, MA 02115 USA

[15] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[16] Providence VA Healthcare Syst, Dept Med, Cardiol, Providence, RI USA

[17] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA

[18] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA

[19] Yale Univ, Sch Med, Yale Ctr Med Informat, New Haven, CT USA

[20] Yale Univ, Sch Med, Div Human Genet, Dept Psychiat, New Haven, CT USA

[21] Yale Univ, Sch Med, Dept Computat Biol & Bioinformat, New Haven, CT USA

[22] Clin Epidemiol Res Ctr CERC, West Haven, CT USA

[23] VA Connecticut Healthcare Syst, West Haven, CT USA

[24] Massachusetts Gen Hosp, Med, Gen Internal Med, Boston, MA 02114 USA

[25] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[26] Emory Univ, Sch Publ Hlth, Epidemiol, Atlanta, GA USA

[27] Emory Univ, Atlanta, GA USA

[28] Atlanta VA Healthcare Syst, Decatur, GA USA

[29] Phoenix VA Healthcare Syst, Dept Med, Phoenix, AZ USA

[30] Univ Arizona, Coll Med, Phoenix, AZ USA

[31] Providence VA Med Ctr, Dept Psychiat & Human Behav, Providence, RI USA

[32] Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA

[33] Durham VA Med Ctr, Dept Med, Gastroenterol, Durham, NC USA

[34] Duke Univ, Dept Med, Gastroenterol, Durham, NC USA

[35] VA Salt Lake City Healthcare Syst, VA Informat & Comp Infrastruct VINCI, Salt Lake City, UT USA

[36] Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA

[37] Univ Utah, Sch Med, Internal Med, Epidemiol, Salt Lake City, UT USA

[38] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cardiovasc Dis Initiat, Cambridge, MA USA

[39] Univ Calif San Francisco, San Francisco VA Healthcare Syst, Med Pulm & Crit Care, San Francisco, CA 94143 USA

[40] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA

[41] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[42] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[43] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA

[44] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

[45] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[46] Univ Arizona, Epidemiol & Biostat, Tucson, AZ USA

[47] Infect Dis Sect, Cleveland, OH USA

[48] Louis Stokes Cleveland VAMed Ctr, Cleveland, OH USA

[49] Argonne Natl Lab, Data Sci & Learning, Lemont, IL USA

[50] VA Palo Alto Hlth Care Syst, Precis Med, Palo Alto, CA USA

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2022年 / 206卷 / 10期

基金：

美国国家卫生研究院;

关键词：

coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; idiopathic pulmonary fibrosis; electronic health records; genetic association; IDIOPATHIC PULMONARY-FIBROSIS; PROMOTER POLYMORPHISM; DISTAL AIRWAYS; HEALTH; ASSOCIATION; PNEUMONIA; SURVIVAL; RISK;

D O I：

10.1164/rccm.202109-2166OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (N-cases = 4,325; N-controls = 507,640; OR= 0.89 [0.82-0.97]; P = 6.86x10(-3)) and joint meta-analyses with the HGI (N-cases = 13,320; N-controls = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99x10(-5)). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (N-cases = 19,168/N-controls = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P, 0.05) in the joint metaanalysis with the HGI (N-cases = 44,820; N-controls = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

引用

页码：1220 / 1229

页数：10

共 43 条

[1] Association between acute respiratory disease events and the MUC5B promoter polymorphism in smokers
Ash, Samuel Y.
Harmouche, Rola
Putman, Rachel K.
Ross, James C.
Martinez, Fernando J.
Choi, Augustine M.
Bowler, Russell P.
Regan, Elizabeth A.
Curtis, Jeffrey L.
Han, MeiLan K.
Boucher, Richard C.
O'Neal, Wanda K.
Hatabu, Hiroto
Lynch, David A.
Rosas, Ivan O.
Hunninghake, Gary M.
Estepar, Raul San Jose
Washko, George R.
[J]. THORAX, 2018, 73 (11) : 1071 - 1074
[2] Second-generation PLINK: rising to the challenge of larger and richer datasets
Chang, Christopher C.
Chow, Carson C.
Tellier, Laurent C. A. M.
Vattikuti, Shashaank
Purcell, Shaun M.
Lee, James J.
[J]. GIGASCIENCE, 2015, 4
[3] Mucins MUC5B and MUC5AC in Distal Airways and Honeycomb Spaces: Comparison among Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia, Fibrotic Nonspecific Interstitial Pneumonitis, and Control Lungs
Conti, Caterina
Montero-Fernandez, Angeles
Borg, Elaine
Osadolor, Tina
Viola, Patrizia
De Lauretis, Angelo
Stock, Carmel J.
Bonifazi, Martina
Bonini, Matteo
Caramori, Gaetano
Lindahl, Gisela
Blasi, Francesco B.
Nicholson, Andrew G.
Wells, Athol U.
Sestini, Piersante
Renzoni, Elisabetta
[J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2016, 193 (04) : 462 - 464
[4] PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations
Denny, Joshua C.
Ritchie, Marylyn D.
Basford, Melissa A.
Pulley, Jill M.
Bastarache, Lisa
Brown-Gentry, Kristin
Wang, Deede
Masys, Dan R.
Roden, Dan M.
Crawford, Dana C.
[J]. BIOINFORMATICS, 2010, 26 (09) : 1205 - 1210
[5] An interactive web-based dashboard to track COVID-19 in real time
Dong, Ensheng
Du, Hongru
Gardner, Lauren
[J]. LANCET INFECTIOUS DISEASES, 2020, 20 (05) : 533 - 534
[6] Adjustment for index event bias in genome-wide association studies of subsequent events
Dudbridge, Frank
Allen, Richard J.
Sheehan, Nuala A.
Schmidt, A. Floriaan
Lee, James C.
Jenkins, R. Gisli
Wain, Louise V.
Hingorani, Aroon D.
Patel, Riyaz S.
[J]. NATURE COMMUNICATIONS, 2019, 10 (1)
[7] IDIOPATHIC PULMONARY FIBROSIS: A GENETIC DISEASE THAT INVOLVES MUCOCILIARY DYSFUNCTION OF THE PERIPHERAL AIRWAYS
Evans, Christopher M.
Fingerlin, Tasha E.
Schwarz, Marvin I.
Lynch, David
Kurche, Jonathan
Warg, Laura
Yang, Ivana V.
Schwartz, David A.
[J]. PHYSIOLOGICAL REVIEWS, 2016, 96 (04) : 1567 - 1591
[8] Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity
Fadista, Joao
Kraven, Luke M.
Karjalainen, Juha
Andrews, Shea J.
Geller, Frank
Baillie, J. Kenneth
Wain, Louise, V
Jenkins, R. Gisli
Feenstra, Bjarke
[J]. EBIOMEDICINE, 2021, 65
[9] Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies
Fang, Huaying
Hui, Qin
Lynch, Julie
Honerlaw, Jacqueline
Assimes, Themistocles L.
Huang, Jie
Vujkovic, Marijana
Damrauer, Scott M.
Pyarajan, Saiju
Gaziano, J. Michael
DuVall, Scott L.
O'Donnell, Christopher J.
Cho, Kelly
Chang, Kyong-Mi
Wilson, Peter W. F.
Tsao, Philip S.
Sun, Yan V.
Tang, Hua
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2019, 105 (04) : 763 - 772
[10] The MUC5B-associated variant rs35705950 resides within an enhancer subject to lineage- and disease-dependent epigenetic remodeling
Gally, Fabienne
Sasse, Sarah K.
Kurche, Jonathan S.
Gruca, Margaret A.
Cardwell, Jonathan H.
Okamoto, Tsukasa
Chu, Hong W.
Hou, Xiaomeng
Poirion, Olivier B.
Buchanan, Justin
Preissl, Sebastian
Ren, Bing
Colgan, Sean P.
Dowell, Robin D.
Yang, Ivana, V
Schwartz, David A.
Gerber, Anthony N.
[J]. JCI INSIGHT, 2021, 6 (02)

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