IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31626-4.html
   My bibliography  Save this article

Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity

Author

Listed:
  • James J. Gilchrist

    (University of Oxford
    University of Oxford
    University of Oxford)

  • Seiko Makino

    (University of Oxford)

  • Vivek Naranbhai

    (University of Oxford)

  • Piyush K. Sharma

    (University of Oxford
    University of Oxford)

  • Surya Koturan

    (University of Oxford
    University of Oxford)

  • Orion Tong

    (University of Oxford
    University of Oxford)

  • Chelsea A. Taylor

    (University of Oxford
    University of Oxford)

  • Robert A. Watson

    (University of Oxford
    University of Oxford)

  • Alba Verge los Aires

    (University of Oxford
    University of Oxford)

  • Rosalin Cooper

    (University of Oxford
    University of Oxford)

  • Evelyn Lau

    (University of Oxford)

  • Sara Danielli

    (University of Oxford)

  • Dan Hameiri-Bowen

    (University of Oxford)

  • Wanseon Lee

    (University of Oxford)

  • Esther Ng

    (University of Oxford)

  • Justin Whalley

    (University of Oxford)

  • Julian C. Knight

    (University of Oxford
    University of Oxford)

  • Benjamin P. Fairfax

    (University of Oxford
    University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

Abstract

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.

Suggested Citation

  • James J. Gilchrist & Seiko Makino & Vivek Naranbhai & Piyush K. Sharma & Surya Koturan & Orion Tong & Chelsea A. Taylor & Robert A. Watson & Alba Verge los Aires & Rosalin Cooper & Evelyn Lau & Sara D, 2022. "Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31626-4
    DOI: 10.1038/s41467-022-31626-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31626-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31626-4?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. Olivier Delaneau & Halit Ongen & Andrew A. Brown & Alexandre Fort & Nikolaos I. Panousis & Emmanouil T. Dermitzakis, 2017. "A complete tool set for molecular QTL discovery and analysis," Nature Communications, Nature, vol. 8(1), pages 1-7, August.
    2. 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.
    3. Alessia Visconti & David L. Duffy & Fan Liu & Gu Zhu & Wenting Wu & Yan Chen & Pirro G. Hysi & Changqing Zeng & Marianna Sanna & Mark M. Iles & Peter A. Kanetsky & Florence Demenais & Merel A. Hamer &, 2018. "Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    4. Talib Hassan Ali & Simona Pisanti & Elena Ciaglia & Roberta Mortarini & Andrea Anichini & Cinzia Garofalo & Rossana Tallerico & Mario Santinami & Elio Gulletta & Caterina Ietto & Mario Galgani & Giuse, 2014. "Enrichment of CD56dimKIR+CD57+ highly cytotoxic NK cells in tumour-infiltrated lymph nodes of melanoma patients," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    5. Yukinori Okada & Di Wu & Gosia Trynka & Towfique Raj & Chikashi Terao & Katsunori Ikari & Yuta Kochi & Koichiro Ohmura & Akari Suzuki & Shinji Yoshida & Robert R. Graham & Arun Manoharan & Ward Ortman, 2014. "Genetics of rheumatoid arthritis contributes to biology and drug discovery," Nature, Nature, vol. 506(7488), pages 376-381, February.
    6. Heather J. Cordell & Younghun Han & George F. Mells & Yafang Li & Gideon M. Hirschfield & Casey S. Greene & Gang Xie & Brian D. Juran & Dakai Zhu & David C. Qian & James A. B. Floyd & Katherine I. Mor, 2015. "International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    7. Vivek Naranbhai & Benjamin P. Fairfax & Seiko Makino & Peter Humburg & Daniel Wong & Esther Ng & Adrian V. S. Hill & Julian C. Knight, 2015. "Genomic modulators of gene expression in human neutrophils," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    8. Eoin F. McKinney & Iona Cuthbertson & Kristina M. Harris & Dawn E. Smilek & Christopher Connor & Giulia Manferrari & Edward J. Carr & Scott S. Zamvil & Kenneth G. C. Smith, 2021. "A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    9. Harvind S. Chahal & Yuan Lin & Katherine J. Ransohoff & David A. Hinds & Wenting Wu & Hong-Ji Dai & Abrar A. Qureshi & Wen-Qing Li & Peter Kraft & Jean Y. Tang & Jiali Han & Kavita Y. Sarin, 2016. "Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma," Nature Communications, Nature, vol. 7(1), pages 1-8, November.
    10. Bryan N Howie & Peter Donnelly & Jonathan Marchini, 2009. "A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-15, June.
    11. John D. Storey, 2002. "A direct approach to false discovery rates," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 64(3), pages 479-498, August.
    Full references (including those not matched with items on IDEAS)

    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. 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.
    2. Elizabeth C. Goode & Laura Fachal & Nikolaos Panousis & Loukas Moutsianas & Rebecca E. McIntyre & Benjamin Yu Hang Bai & Norihito Kawasaki & Alexandra Wittmann & Tim Raine & Simon M. Rushbrook & Carl , 2024. "Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Satria P. Sajuthi & Jamie L. Everman & Nathan D. Jackson & Benjamin Saef & Cydney L. Rios & Camille M. Moore & Angel C. Y. Mak & Celeste Eng & Ana Fairbanks-Mahnke & Sandra Salazar & Jennifer Elhawary, 2022. "Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Anneke Brümmer & Sven Bergmann, 2024. "Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Antje Häder & Sascha Schäuble & Jan Gehlen & Nadja Thielemann & Benedikt C. Buerfent & Vitalia Schüller & Timo Hess & Thomas Wolf & Julia Schröder & Michael Weber & Kerstin Hünniger & Jürgen Löffler &, 2023. "Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. 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.
    8. Sébastien Thériault & Zhonglin Li & Erik Abner & Jian’an Luan & Hasanga D. Manikpurage & Ursula Houessou & Pardis Zamani & Mewen Briend & Dominique K. Boudreau & Nathalie Gaudreault & Lily Frenette & , 2024. "Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Jayshree Advani & Puja A. Mehta & Andrew R. Hamel & Sudeep Mehrotra & Christina Kiel & Tobias Strunz & Ximena Corso-Díaz & Madeline Kwicklis & Freekje Asten & Rinki Ratnapriya & Emily Y. Chew & Dena G, 2024. "QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    10. Taehyeung Kim & Marta Martínez-Bonet & Qiang Wang & Nicolaj Hackert & Jeffrey A. Sparks & Yuriy Baglaenko & Byunghee Koh & Roxane Darbousset & Raquel Laza-Briviesca & Xiaoting Chen & Vitor R. C. Aguia, 2024. "Non-coding autoimmune risk variant defines role for ICOS in T peripheral helper cell development," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Francesco Bettella & Andrew A Brown & Olav B Smeland & Yunpeng Wang & Aree Witoelar & Alfonso A Buil Demur & Wesley K Thompson & Verena Zuber & Anders M Dale & Srdjan Djurovic & Ole A Andreassen, 2018. "Cross-tissue eQTL enrichment of associations in schizophrenia," PLOS ONE, Public Library of Science, vol. 13(9), pages 1-17, September.
    12. Gianmarco Mignogna & Caitlin E. Carey & Robbee Wedow & Nikolas Baya & Mattia Cordioli & Nicola Pirastu & Rino Bellocco & Kathryn Fiuza Malerbi & Michel G. Nivard & Benjamin M. Neale & Raymond K. Walte, 2023. "Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci," Nature Human Behaviour, Nature, vol. 7(8), pages 1371-1387, August.
    13. María Gordillo-Marañón & Magdalena Zwierzyna & Pimphen Charoen & Fotios Drenos & Sandesh Chopade & Tina Shah & Jorgen Engmann & Nishi Chaturvedi & Olia Papacosta & Goya Wannamethee & Andrew Wong & Ree, 2021. "Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    14. 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.
    15. 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.
    16. Tina Roostaei & Hans-Ulrich Klein & Yiyi Ma & Daniel Felsky & Pia Kivisäkk & Sarah M. Connor & Alexandra Kroshilina & Christina Yung & Belinda J. Kaskow & Xiaorong Shao & Brooke Rhead & José M. Ordová, 2021. "Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    17. Thorunn A. Olafsdottir & Gudmar Thorleifsson & Aitzkoa Lopez de Lapuente Portilla & Stefan Jonsson & Lilja Stefansdottir & Abhishek Niroula & Aslaug Jonasdottir & Hannes P. Eggertsson & Gisli H. Halld, 2024. "Sequence variants influencing the regulation of serum IgG subclass levels," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Beomsu Kim & Dan Say Kim & Joong-Gon Shin & Sangseob Leem & Minyoung Cho & Hanji Kim & Ki-Nam Gu & Jung Yeon Seo & Seung Won You & Alicia R. Martin & Sun Gyoo Park & Yunkwan Kim & Choongwon Jeong & Na, 2024. "Mapping and annotating genomic loci to prioritize genes and implicate distinct polygenic adaptations for skin color," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Chuan Gao & Nan Wang & Xiuqing Guo & Julie T Ziegler & Kent D Taylor & Anny H Xiang & Yang Hai & Steven J Kridel & Jerry L Nadler & Fouad Kandeel & Leslie J Raffel & Yii-Der I Chen & Jill M Norris & J, 2015. "A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-17, November.

    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:13:y:2022:i:1:d:10.1038_s41467-022-31626-4. 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.