IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26888-3.html
   My bibliography  Save this article

COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types

Author

Listed:
  • Benjamin J. Schmiedel

    (La Jolla Institute for Immunology)

  • Job Rocha

    (La Jolla Institute for Immunology
    National Autonomous University of Mexico, Cuernavaca)

  • Cristian Gonzalez-Colin

    (La Jolla Institute for Immunology
    National Autonomous University of Mexico, Cuernavaca)

  • Sourya Bhattacharyya

    (La Jolla Institute for Immunology)

  • Ariel Madrigal

    (La Jolla Institute for Immunology)

  • Christian H. Ottensmeier

    (La Jolla Institute for Immunology
    University of Liverpool)

  • Ferhat Ay

    (La Jolla Institute for Immunology
    University of California San Diego)

  • Vivek Chandra

    (La Jolla Institute for Immunology)

  • Pandurangan Vijayanand

    (La Jolla Institute for Immunology
    University of Liverpool
    University of California San Diego)

Abstract

Common genetic polymorphisms associated with COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Given the importance of immune cells in the pathogenesis of COVID-19 illness, here we assessed the effects of COVID-19-risk variants on gene expression in a wide range of immune cell types. Transcriptome-wide association study and colocalization analysis revealed putative causal genes and the specific immune cell types where gene expression is most influenced by COVID-19-risk variants. Notable examples include OAS1 in non-classical monocytes, DTX1 in B cells, IL10RB in NK cells, CXCR6 in follicular helper T cells, CCR9 in regulatory T cells and ARL17A in TH2 cells. By analysis of transposase accessible chromatin and H3K27ac-based chromatin-interaction maps of immune cell types, we prioritized potentially functional COVID-19-risk variants. Our study highlights the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations.

Suggested Citation

  • Benjamin J. Schmiedel & Job Rocha & Cristian Gonzalez-Colin & Sourya Bhattacharyya & Ariel Madrigal & Christian H. Ottensmeier & Ferhat Ay & Vivek Chandra & Pandurangan Vijayanand, 2021. "COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26888-3
    DOI: 10.1038/s41467-021-26888-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26888-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-26888-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Inge Van de Walle & Anne-Catherine Dolens & Kaat Durinck & Katrien De Mulder & Wouter Van Loocke & Sagar Damle & Els Waegemans & Jelle De Medts & Imke Velghe & Magda De Smedt & Bart Vandekerckhove & T, 2016. "GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    3. Helena Kilpinen & Angela Goncalves & Andreas Leha & Vackar Afzal & Kaur Alasoo & Sofie Ashford & Sendu Bala & Dalila Bensaddek & Francesco Paolo Casale & Oliver J. Culley & Petr Danecek & Adam Faulcon, 2017. "Common genetic variation drives molecular heterogeneity in human iPSCs," Nature, Nature, vol. 546(7658), pages 370-375, June.
    4. Alvaro N. Barbeira & Scott P. Dickinson & Rodrigo Bonazzola & Jiamao Zheng & Heather E. Wheeler & Jason M. Torres & Eric S. Torstenson & Kaanan P. Shah & Tzintzuni Garcia & Todd L. Edwards & Eli A. St, 2018. "Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics," Nature Communications, Nature, vol. 9(1), pages 1-20, December.
    5. Qin Qin Huang & Howard H. F. Tang & Shu Mei Teo & Danny Mok & Scott C. Ritchie & Artika P. Nath & Marta Brozynska & Agus Salim & Andrew Bakshi & Barbara J. Holt & Chiea Chuen Khor & Peter D. Sly & Pat, 2020. "Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    6. Helena Kilpinen & Angela Goncalves & Andreas Leha & Vackar Afzal & Kaur Alasoo & Sofie Ashford & Sendu Bala & Dalila Bensaddek & Francesco Paolo Casale & Oliver J. Culley & Petr Danecek & Adam Faulcon, 2017. "Correction: Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs," Nature, Nature, vol. 546(7660), pages 686-686, June.
    7. Erola Pairo-Castineira & Sara Clohisey & Lucija Klaric & Andrew D. Bretherick & Konrad Rawlik & Dorota Pasko & Susan Walker & Nick Parkinson & Max Head Fourman & Clark D. Russell & James Furniss & Ann, 2021. "Genetic mechanisms of critical illness in COVID-19," Nature, Nature, vol. 591(7848), pages 92-98, March.
    8. Benjamin B. Sun & Joseph C. Maranville & James E. Peters & David Stacey & James R. Staley & James Blackshaw & Stephen Burgess & Tao Jiang & Ellie Paige & Praveen Surendran & Clare Oliver-Williams & Mi, 2018. "Genomic atlas of the human plasma proteome," Nature, Nature, vol. 558(7708), pages 73-79, June.
    9. Augustine Kong & Gudmar Thorleifsson & Daniel F. Gudbjartsson & Gisli Masson & Asgeir Sigurdsson & Aslaug Jonasdottir & G. Bragi Walters & Adalbjorg Jonasdottir & Arnaldur Gylfason & Kari Th. Kristins, 2010. "Fine-scale recombination rate differences between sexes, populations and individuals," Nature, Nature, vol. 467(7319), pages 1099-1103, October.
    10. Alvaro N Barbeira & Milton Pividori & Jiamao Zheng & Heather E Wheeler & Dan L Nicolae & Hae Kyung Im, 2019. "Integrating predicted transcriptome from multiple tissues improves association detection," PLOS Genetics, Public Library of Science, vol. 15(1), pages 1-20, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Sourya Bhattacharyya & Ferhat Ay, 2024. "Identifying genetic variants associated with chromatin looping and genome function," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Angela Andaleon & Lauren S Mogil & Heather E Wheeler, 2019. "Genetically regulated gene expression underlies lipid traits in Hispanic cohorts," PLOS ONE, Public Library of Science, vol. 14(8), pages 1-21, August.
    2. Ashley Budu-Aggrey & Anna Kilanowski & Maria K. Sobczyk & Suyash S. Shringarpure & Ruth Mitchell & Kadri Reis & Anu Reigo & Reedik Mägi & Mari Nelis & Nao Tanaka & Ben M. Brumpton & Laurent F. Thomas , 2023. "European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Matthew Tegtmeyer & Jatin Arora & Samira Asgari & Beth A. Cimini & Ajay Nadig & Emily Peirent & Dhara Liyanage & Gregory P. Way & Erin Weisbart & Aparna Nathan & Tiffany Amariuta & Kevin Eggan & Marzi, 2024. "High-dimensional phenotyping to define the genetic basis of cellular morphology," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Magdalena Zimoń & Yunfeng Huang & Anthi Trasta & Aliaksandr Halavatyi & Jimmy Z. Liu & Chia-Yen Chen & Peter Blattmann & Bernd Klaus & Christopher D. Whelan & David Sexton & Sally John & Wolfgang Hube, 2021. "Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    5. Grace Png & Andrei Barysenka & Linda Repetto & Pau Navarro & Xia Shen & Maik Pietzner & Eleanor Wheeler & Nicholas J. Wareham & Claudia Langenberg & Emmanouil Tsafantakis & Maria Karaleftheri & George, 2021. "Mapping the serum proteome to neurological diseases using whole genome sequencing," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    6. Chang Lu & Jan Zaucha & Rihab Gam & Hai Fang & Smithers & Matt E. Oates & Miguel Bernabe-Rubio & James Williams & Natalie Zelenka & Arun Prasad Pandurangan & Himani Tandon & Hashem Shihab & Raju Kalai, 2023. "Hypothesis-free phenotype prediction within a genetics-first framework," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Valur Emilsson & Elias F. Gudmundsson & Thorarinn Jonmundsson & Brynjolfur G. Jonsson & Michael Twarog & Valborg Gudmundsdottir & Zhiguang Li & Nancy Finkel & Stephen Poor & Xin Liu & Robert Esterberg, 2022. "A proteogenomic signature of age-related macular degeneration in blood," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. David Stacey & Lingyan Chen & Paulina J. Stanczyk & Joanna M. M. Howson & Amy M. Mason & Stephen Burgess & Stephen MacDonald & Jonathan Langdown & Harriett McKinney & Kate Downes & Neda Farahi & James, 2022. "Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Molly Went & Laura Duran-Lozano & Gisli H. Halldorsson & Andrea Gunnell & Nerea Ugidos-Damboriena & Philip Law & Ludvig Ekdahl & Amit Sud & Gudmar Thorleifsson & Malte Thodberg & Thorunn Olafsdottir &, 2024. "Deciphering the genetics and mechanisms of predisposition to multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Andrew A. Brown & Juan J. Fernandez-Tajes & Mun-gwan Hong & Caroline A. Brorsson & Robert W. Koivula & David Davtian & Théo Dupuis & Ambra Sartori & Theodora-Dafni Michalettou & Ian M. Forgie & Jonath, 2023. "Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Amil M. Shah & Peder L. Myhre & Victoria Arthur & Pranav Dorbala & Humaira Rasheed & Leo F. Buckley & Brian Claggett & Guning Liu & Jianzhong Ma & Ngoc Quynh Nguyen & Kunihiro Matsushita & Chiadi Ndum, 2024. "Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Maik Pietzner & Eleanor Wheeler & Julia Carrasco-Zanini & Nicola D. Kerrison & Erin Oerton & Mine Koprulu & Jian’an Luan & Aroon D. Hingorani & Steve A. Williams & Nicholas J. Wareham & Claudia Langen, 2021. "Synergistic insights into human health from aptamer- and antibody-based proteomic profiling," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    13. Xena Marie Mapel & Naveen Kumar Kadri & Alexander S. Leonard & Qiongyu He & Audald Lloret-Villas & Meenu Bhati & Maya Hiltpold & Hubert Pausch, 2024. "Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Diptavo Dutta & Yuan He & Ashis Saha & Marios Arvanitis & Alexis Battle & Nilanjan Chatterjee, 2022. "Aggregative trans-eQTL analysis detects trait-specific target gene sets in whole blood," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. William J. Young & Jeffrey Haessler & Jan-Walter Benjamins & Linda Repetto & Jie Yao & Aaron Isaacs & Andrew R. Harper & Julia Ramirez & Sophie Garnier & Stefan Duijvenboden & Antoine R. Baldassari & , 2023. "Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Yaohua Yang & Yaxin Chen & Shuai Xu & Xingyi Guo & Guochong Jia & Jie Ping & Xiang Shu & Tianying Zhao & Fangcheng Yuan & Gang Wang & Yufang Xie & Hang Ci & Hongmo Liu & Yawen Qi & Yongjun Liu & Dan L, 2024. "Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    17. Xinyuan Dong & Yu-Ru Su & Richard Barfield & Stephanie A Bien & Qianchuan He & Tabitha A Harrison & Jeroen R Huyghe & Temitope O Keku & Noralane M Lindor & Clemens Schafmayer & Andrew T Chan & Stephen, 2020. "A general framework for functionally informed set-based analysis: Application to a large-scale colorectal cancer study," PLOS Genetics, Public Library of Science, vol. 16(8), pages 1-21, August.
    18. Qiliang Ding & Matthew M. Edwards & Ning Wang & Xiang Zhu & Alexa N. Bracci & Michelle L. Hulke & Ya Hu & Yao Tong & Joyce Hsiao & Christine J. Charvet & Sulagna Ghosh & Robert E. Handsaker & Kevin Eg, 2021. "The genetic architecture of DNA replication timing in human pluripotent stem cells," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    19. Yanyu Xiao & Jingjing Wang & Jiaqi Li & Peijing Zhang & Jingyu Li & Yincong Zhou & Qing Zhou & Ming Chen & Xin Sheng & Zhihong Liu & Xiaoping Han & Guoji Guo, 2023. "An analytical framework for decoding cell type-specific genetic variation of gene regulation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    20. Drew R. Neavin & Angela M. Steinmann & Nona Farbehi & Han Sheng Chiu & Maciej S. Daniszewski & Himanshi Arora & Yasmin Bermudez & Cátia Moutinho & Chia-Ling Chan & Monique Bax & Mubarika Tyebally & Vi, 2023. "A village in a dish model system for population-scale hiPSC studies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26888-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.