Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

被引：57

作者：

Povysil, Gundula ^{[1
]}

Butler-Laporte, Guillaume ^{[2
,3
]}

Shang, Ning ^{[4
]}

Wang, Chen ^{[4
]}

Khan, Atlas ^{[4
]}

Alaamery, Manal ^{[5
,6
]}

Nakanishi, Tomoko ^{[2
,7
,8
]}

Zhou, Sirui ^{[2
]}

Forgetta, Vincenzo ^{[2
]}

Eveleigh, Robert J. M. ^{[9
,10
]}

Bourgey, Mathieu ^{[9
,10
]}

Aziz, Naveed ^{[11
]}

Jones, Steven J. M. ^{[11
]}

Knoppers, Bartha ^{[11
]}

Scherer, Stephen W. ^{[11
]}

Strug, Lisa J. ^{[11
]}

Lepage, Pierre ^{[12
]}

Ragoussis, Jiannis ^{[7
,12
]}

Bourque, Guillaume ^{[7
,10
,12
]}

Alghamdi, Jahad ^{[13
]}

Aljawini, Nora ^{[14
]}

Albes, Nour ^{[14
]}

Al-Afghani, Hani M. ^{[15
]}

Alghamdi, Bader ^{[5
]}

Almutairi, Mansour S. ^{[5
]}

Mahmoud, Ebrahim Sabri ^{[16
,17
]}

Abu-Safieh, Leen ^{[18
,19
]}

El Bardisy, Hadeel ^{[18
,19
]}

Harthi, Fawz S. Al ^{[18
,19
]}

Alshareef, Abdulraheem ^{[20
]}

Suliman, Bandar Ali ^{[20
]}

Alqahtani, Saleh A. ^{[21
,22
]}

Almalik, Abdulaziz ^{[23
]}

Alrashed, May M. ^{[24
]}

Massadeh, Salam ^{[5
,6
]}

Mooser, Vincent ^{[7
]}

Lathrop, Mark ^{[7
,11
,12
]}

Fawzy, Mohamed ^{[18
,19
]}

Arabi, Yaseen M. ^{[16
,17
]}

Mbarek, Hamdi ^{[25
]}

Saad, Chadi ^{[25
]}

Al-Muftah, Wadha ^{[25
]}

Jung, Junghyun ^{[26
,27
]}

Mangul, Serghei ^{[26
]}

Badji, Radja ^{[25
]}

Al Thani, Asma ^{[25
]}

Ismail, Said I. ^{[25
]}

Gharavi, Ali G. ^{[1
,2
,3
,4
,28
]}

Abedalthagafi, Malak S. ^{[18
,19
]}

Richards, J. Brent ^{[2
,3
,8
,29
]}

机构：

[1] Columbia Univ, Inst Genom Med, New York, NY USA

[2] Lady Davis Inst Med Res, Montreal, PQ, Canada

[3] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada

[4] Columbia Univ, Vagelos Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY USA

[5] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Dev Med Dept, King Abdulaziz Med City,Minist Natl Guard Hlth Af, Riyadh, Saudi Arabia

[6] King Abdulaziz City Sci & Technol, Saudi Human Genome Project, Riyadh, Saudi Arabia

[7] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[8] Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto, Japan

[9] McGill Univ, Canadian Ctr Computat Genom, Montreal, PQ, Canada

[10] McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada

[11] Canadian COVID Genom Network, HostSeq Project, Ottawa, ON, Canada

[12] McGill Univ, Canadian Ctr Computat Genom, Montreal, PQ, Canada

[13] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Minist Natl Guard Hlth Affairs, Saudi Biobank, Riyadh, Saudi Arabia

[14] King Abdulaziz City Sci & Technol, Joint Centers Excellence Program, BWH Ctr Excellence Biomed, KACST, Riyadh, Saudi Arabia

[15] Secur Forces Hosp, Minist Interior, Lab Dept, Med Serv, Mecca, Saudi Arabia

[16] King Abdullah Int Med Res Ctr, Minist Natl Guard Hlth Affairs, Riyadh, Saudi Arabia

[17] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia

[18] King Fahad Med City, Saudi Human Genome Project, Genom Res Dept, Riyadh, Saudi Arabia

[19] King Abdulaziz City Sci & Technol, Riyadh, Saudi Arabia

[20] Taibah Univ, Coll Appl Med Sci, Madina, Saudi Arabia

[21] King Faisal Specialist Hosp & Res Ctr, Liver Transplant Unit, Riyadh, Saudi Arabia

[22] Johns Hopkins Univ, Div Gastroenterol & Hepatol, Baltimore, MD USA

[23] King Abdulaziz City Sci & Technol, Life Sci & Environm Inst, Riyadh, Saudi Arabia

[24] King Saud Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Riyadh, Saudi Arabia

[25] Qatar Fdn, Qatar Fdn Res Dev & Innovat, Qatar Genome Program, Doha, Qatar

[26] Univ Southern Calif, Sch Pharm, Dept Clin Pharm, Los Angeles, CA USA

[27] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA

[28] Columbia Univ, Vagelos Coll Phys & Surg, Dept Med, Ctr Precis Med & Genom, New York, NY USA

[29] Kings Coll London, Dept Twin Res, London, England

[30] Columbia Univ, Dept Genet & Dev, New York, NY USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2021年 / 131卷 / 14期

基金：

日本学术振兴会; 加拿大健康研究院;

关键词：

D O I：

10.1172/JCI147834

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3-and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

引用

页数：7

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