IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27427-w.html
   My bibliography  Save this article

Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome

Author

Listed:
  • Tina Roostaei

    (Columbia University Irving Medical Center)

  • Hans-Ulrich Klein

    (Columbia University Irving Medical Center)

  • Yiyi Ma

    (Columbia University Irving Medical Center)

  • Daniel Felsky

    (University of Toronto)

  • Pia Kivisäkk

    (Massachusetts General Hospital)

  • Sarah M. Connor

    (Columbia University Irving Medical Center)

  • Alexandra Kroshilina

    (Columbia University Irving Medical Center)

  • Christina Yung

    (Columbia University Irving Medical Center)

  • Belinda J. Kaskow

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Xiaorong Shao

    (University of California)

  • Brooke Rhead

    (University of California)

  • José M. Ordovás

    (Tufts University)

  • Devin M. Absher

    (HudsonAlpha Institute for Biotechnology)

  • Donna K. Arnett

    (University of Kentucky)

  • Jia Liu

    (City University of New York)

  • Nikolaos Patsopoulos

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Lisa F. Barcellos

    (University of California)

  • Howard L. Weiner

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Philip L. De Jager

    (Columbia University Irving Medical Center)

Abstract

Identifying the effects of genetic variation on the epigenome in disease-relevant cell types can help advance our understanding of the first molecular contributions of genetic susceptibility to disease onset. Here, we establish a genome-wide map of DNA methylation quantitative trait loci in CD4+ T-cells isolated from multiple sclerosis patients. Utilizing this map in a colocalization analysis, we identify 19 loci where the same haplotype drives both multiple sclerosis susceptibility and local DNA methylation. We also identify two distant methylation effects of multiple sclerosis susceptibility loci: a chromosome 16 locus affects PRDM8 methylation (a chromosome 4 region not previously associated with multiple sclerosis), and the aggregate effect of multiple sclerosis-associated variants in the major histocompatibility complex influences DNA methylation near PRKCA (chromosome 17). Overall, we present a new resource for a key cell type in inflammatory disease research and uncover new gene targets for the study of predisposition to multiple sclerosis.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27427-w
    DOI: 10.1038/s41467-021-27427-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27427-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27427-w?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. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    4. Lara Kular & Yun Liu & Sabrina Ruhrmann & Galina Zheleznyakova & Francesco Marabita & David Gomez-Cabrero & Tojo James & Ewoud Ewing & Magdalena Lindén & Bartosz Górnikiewicz & Shahin Aeinehband & Per, 2018. "DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    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. 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.
    2. Fasil Tekola-Ayele & Xuehuo Zeng & Suvo Chatterjee & Marion Ouidir & Corina Lesseur & Ke Hao & Jia Chen & Markos Tesfaye & Carmen J. Marsit & Tsegaselassie Workalemahu & Ronald Wapner, 2022. "Placental multi-omics integration identifies candidate functional genes for birthweight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Lynne Krohn & Karl Heilbron & Cornelis Blauwendraat & Regina H. Reynolds & Eric Yu & Konstantin Senkevich & Uladzislau Rudakou & Mehrdad A. Estiar & Emil K. Gustavsson & Kajsa Brolin & Jennifer A. Rus, 2022. "Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. 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.
    6. 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.
    7. 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.
    8. Richard Burns & William J. Young & Nay Aung & Luis R. Lopes & Perry M. Elliott & Petros Syrris & Roberto Barriales-Villa & Catrin Sohrabi & Steffen E. Petersen & Julia Ramírez & Alistair Young & Patri, 2024. "Genetic basis of right and left ventricular heart shape," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Hung-Lin Chen & Hsiu-Yin Chiang & David Ray Chang & Chi-Fung Cheng & Charles C. N. Wang & Tzu-Pin Lu & Chien-Yueh Lee & Amrita Chattopadhyay & Yu-Ting Lin & Che-Chen Lin & Pei-Tzu Yu & Chien-Fong Huan, 2024. "Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Danielle Rasooly & Gina M. Peloso & Alexandre C. Pereira & Hesam Dashti & Claudia Giambartolomei & Eleanor Wheeler & Nay Aung & Brian R. Ferolito & Maik Pietzner & Eric H. Farber-Eger & Quinn Stanton , 2023. "Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Priya Gupta & Marco Galimberti & Yue Liu & Sarah Beck & Aliza Wingo & Thomas Wingo & Keyrun Adhikari & Henry R. Kranzler & Murray B. Stein & Joel Gelernter & Daniel F. Levey, 2024. "A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology," Nature Human Behaviour, Nature, vol. 8(11), pages 2235-2249, November.
    12. Seppe Goovaerts & Hanne Hoskens & Ryan J. Eller & Noah Herrick & Anthony M. Musolf & Cristina M. Justice & Meng Yuan & Sahin Naqvi & Myoung Keun Lee & Dirk Vandermeulen & Heather L. Szabo-Rogers & Pau, 2023. "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. 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.
    14. 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.
    15. 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.
    16. Marta Alcalde-Herraiz & Martí Català & Albert Prats-Uribe & Roger Paredes & JunQing Xie & Daniel Prieto-Alhambra, 2024. "Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    17. Bryan R. Gorman & Sun-Gou Ji & Michael Francis & Anoop K. Sendamarai & Yunling Shi & Poornima Devineni & Uma Saxena & Elizabeth Partan & Andrea K. DeVito & Jinyoung Byun & Younghun Han & Xiangjun Xiao, 2024. "Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Arianna Landini & Irena Trbojević-Akmačić & Pau Navarro & Yakov A. Tsepilov & Sodbo Z. Sharapov & Frano Vučković & Ozren Polašek & Caroline Hayward & Tea Petrović & Marija Vilaj & Yurii S. Aulchenko &, 2022. "Genetic regulation of post-translational modification of two distinct proteins," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    19. Benjamin B. Sun & Stephanie J. Loomis & Fabrizio Pizzagalli & Natalia Shatokhina & Jodie N. Painter & Christopher N. Foley & Megan E. Jensen & Donald G. McLaren & Sai Spandana Chintapalli & Alyssa H. , 2022. "Genetic map of regional sulcal morphology in the human brain from UK biobank data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    20. 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.

    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_s41467-021-27427-w. 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.