Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19

被引：70

作者：

Huffman, Jennifer E. ^{[1
]}

Butler-Laporte, Guillaume ^{[2
,3
,4
]}

Khan, Atlas ^{[5
]}

Pairo-Castineira, Erola ^{[6
,7
]}

Drivas, Theodore G. ^{[8
,9
,10
]}

Peloso, Gina M. ^{[1
,11
]}

Nakanishi, Tomoko ^{[12
,13
,14
,15
]}

Ganna, Andrea ^{[16
,17
]}

Verma, Anurag ^{[8
,10
,18
]}

Baillie, J. Kenneth ^{[6
,7
]}

Kiryluk, Krzysztof ^{[5
,19
]}

Richards, J. Brent ^{[2
,3
,4
,20
]}

Zeberg, Hugo ^{[21
,22
]}

机构：

[1] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA

[2] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Med, Montreal, PQ, Canada

[3] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Human Genet, Montreal, PQ, Canada

[4] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada

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

[6] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland

[7] Univ Edinburgh, Western Gen Hosp, Inst Genet & Canc, MRC,Human Genet Unit, Edinburgh, Midlothian, Scotland

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

[9] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA

[10] Univ Penn, Dept Med, Perelman Sch Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA

[11] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

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

[13] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

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

[15] Japan Soc Promot Sci, Tokyo, Japan

[16] Univ Helsinki, Inst Mol Med Finland, Helsinki Inst Life Sci, Helsinki, Finland

[17] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA

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

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

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

[21] Wax Planck Inst Evolutionary Anthropol, Leipzig, Germany

[22] Karolinska Inst, Dept Neurosci, Stockholm, Sweden

来源：

NATURE GENETICS | 2022年 / 54卷 / 02期

基金：

美国国家卫生研究院; 加拿大健康研究院; 英国惠康基金; 英国生物技术与生命科学研究理事会; 瑞典研究理事会; 日本学术振兴会; 英国医学研究理事会;

关键词：

D O I：

10.1038/s41588-021-00996-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity. Multi-ancestry fine-mapping of the OAS1/2/3 region shows that a splice site variant in OAS1 is likely responsible for the association of this locus with the risk of severe COVID-19.

引用

页码：125 / +

页数：7

共 44 条

[1] Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
Jennifer E. Huffman
Guillaume Butler-Laporte
Atlas Khan
Erola Pairo-Castineira
Theodore G. Drivas
Gina M. Peloso
Tomoko Nakanishi
Andrea Ganna
Anurag Verma
J. Kenneth Baillie
Krzysztof Kiryluk
J. Brent Richards
Hugo Zeberg
Nature Genetics, 2022, 54 : 125 - 127
[2] A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
Zhou, Sirui
Butler-Laporte, Guillaume
Nakanishi, Tomoko
Morrison, David R.
Afilalo, Jonathan
Afilalo, Marc
Laurent, Laetitia
Pietzner, Maik
Kerrison, Nicola
Zhao, Kaiqiong
Brunet-Ratnasingham, Elsa
Henry, Danielle
Kimchi, Nofar
Afrasiabi, Zaman
Rezk, Nardin
Bouab, Meriem
Petitjean, Louis
Guzman, Charlotte
Xue, Xiaoqing
Tselios, Chris
Vulesevic, Branka
Adeleye, Olumide
Abdullah, Tala
Almamlouk, Noor
Chen, Yiheng
Chasse, Michael
Durand, Madeleine
Paterson, Clare
Normark, Johan
Frithiof, Robert
Lipcsey, Miklos
Hultstrom, Michael
Greenwood, Celia M. T.
Zeberg, Hugo
Langenberg, Claudia
Thysell, Elin
Pollak, Michael
Mooser, Vincent
Forgetta, Vincenzo
Kaufmann, Daniel E.
Richards, J. Brent
NATURE MEDICINE, 2021, 27 (04) : 659 - 667
[3] A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
Sirui Zhou
Guillaume Butler-Laporte
Tomoko Nakanishi
David R. Morrison
Jonathan Afilalo
Marc Afilalo
Laetitia Laurent
Maik Pietzner
Nicola Kerrison
Kaiqiong Zhao
Elsa Brunet-Ratnasingham
Danielle Henry
Nofar Kimchi
Zaman Afrasiabi
Nardin Rezk
Meriem Bouab
Louis Petitjean
Charlotte Guzman
Xiaoqing Xue
Chris Tselios
Branka Vulesevic
Olumide Adeleye
Tala Abdullah
Noor Almamlouk
Yiheng Chen
Michaël Chassé
Madeleine Durand
Clare Paterson
Johan Normark
Robert Frithiof
Miklós Lipcsey
Michael Hultström
Celia M. T. Greenwood
Hugo Zeberg
Claudia Langenberg
Elin Thysell
Michael Pollak
Vincent Mooser
Vincenzo Forgetta
Daniel E. Kaufmann
J. Brent Richards
Nature Medicine, 2021, 27 : 659 - 667
[4] Human genetics OAS1 links dementia and COVID-19
Israeli, Eitan
ISRAEL MEDICAL ASSOCIATION JOURNAL, 2021, 23 (11): : 707 - 707
[5] A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene
Magusali, Naciye
Graham, Andrew C.
Piers, Thomas M.
Panichnantakul, Pantila
Yaman, Umran
Shoai, Maryam
Reynolds, Regina H.
Botia, Juan A.
Brookes, Keeley J.
Guetta-Baranes, Tamar
Bellou, Eftychia
Bayram, Sevinc
Sokolova, Dimitra
Ryten, Mina
Frigerio, Carlo Sala
Escott-Price, Valentina
Morgan, Kevin
Pocock, Jennifer M.
Hardy, John
Salih, Dervis A.
BRAIN, 2021, 144 : 3727 - 3741
[6] MULTI-ANCESTRY FINE-MAPPING REFINES BIPOLAR DIS-ORDER RISK GENES
Koromina, Maria
Yuan, Kai
Venkatesh, Sanan
O'Connell, Kevin S.
David, Friederike
Coleman, Jonathan
Voloudakis, Georgios
Roussos, Panos
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EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2024, 87 : 11 - 12
[7] Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity
Zheng, Jie
Zhang, Yuemiao
Zhao, Huiling
Liu, Yi
Baird, Denis
Karim, Mohd Anisul
Ghoussaini, Maya
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Roberts, Katherine
Compton, Hannah
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Liu, Xingzi
Wang, Lin
Zhang, Hong
Smith, George Davey
Gaunt, Tom R.
EBIOMEDICINE, 2022, 81
[8] Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions
Jia, Guochong
Chen, Zhishan
Ping, Jie
Cai, Qiuyin
Tao, Ran
Li, Chao
Bauer, Joshua A.
Xie, Yuhan
Ambs, Stefan
Barnard, Mollie E.
Chen, Yu
Choi, Ji-Yeob
Gao, Yu-Tang
Garcia-Closas, Montserrat
Gu, Jian
Hu, Jennifer J.
Iwasaki, Motoki
John, Esther M.
Kweon, Sun-Seog
Li, Christopher I.
Matsuda, Koichi
Matsuo, Keitaro
Nathanson, Katherine L.
Nemesure, Barbara
Olopade, Olufunmilayo I.
Pal, Tuya
Park, Sue K.
Park, Boyoung
Press, Michael F.
Sanderson, Maureen
Sandler, Dale P.
Shen, Chen-Yang
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Brewster, Abenaa M.
Falusi, Adeyinka
Hennis, Anselm J. M.
Ito, Hidemi
Kubo, Michiaki
Lee, Eun-Sook
Makumbi, Timothy
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Noh, Dong-Young
O'Brien, Katie M.
Ojengbede, Oladosu
Olshan, Andrew F.
Park, Min-Ho
Reid, Sonya
NATURE GENETICS, 2025, 57 (01) : 80 - 87
[9] The Immune Response of OAS1, IRF9, and IFI6 Genes in the Pathogenesis of COVID-19
Gajate-Arenas, Malena
Fricke-Galindo, Ingrid
Garcia-Perez, Omar
Dominguez-de-Barros, Angelica
Perez-Rubio, Gloria
Dorta-Guerra, Roberto
Buendia-Roldan, Ivette
Chavez-Galan, Leslie
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (09)
[10] Prevalence of the protective OAS1 rs10774671-G allele against severe COVID-19 in Moroccans: implications for a North African Neanderthal connection
El Yousfi, Fatima Zahra
Haroun, Abbas Ermilo
Nebhani, Chaimae
Belayachi, Jihane
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