IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38389-6.html
   My bibliography  Save this article

Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways

Author

Listed:
  • Pietro Demela

    (Human Technopole)

  • Nicola Pirastu

    (Human Technopole)

  • Blagoje Soskic

    (Human Technopole)

Abstract

Genome-wide association studies (GWAS) have mapped thousands of susceptibility loci associated with immune-mediated diseases. To assess the extent of the genetic sharing across nine immune-mediated diseases we apply genomic structural equation modelling to GWAS data from European populations. We identify three disease groups: gastrointestinal tract diseases, rheumatic and systemic diseases, and allergic diseases. Although loci associated with the disease groups are highly specific, they converge on perturbing the same pathways. Finally, we test for colocalization between loci and single-cell eQTLs derived from peripheral blood mononuclear cells. We identify the causal route by which 46 loci predispose to three disease groups and find evidence for eight genes being candidates for drug repurposing. Taken together, here we show that different constellations of diseases have distinct patterns of genetic associations, but that associated loci converge on perturbing different nodes in T cell activation and signalling pathways.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38389-6
    DOI: 10.1038/s41467-023-38389-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38389-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38389-6?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. Rasa Elmentaite & Natsuhiko Kumasaka & Kenny Roberts & Aaron Fleming & Emma Dann & Hamish W. King & Vitalii Kleshchevnikov & Monika Dabrowska & Sophie Pritchard & Liam Bolt & Sara F. Vieira & Lira Mam, 2021. "Cells of the human intestinal tract mapped across space and time," Nature, Nature, vol. 597(7875), pages 250-255, September.
    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. Joshua Chiou & Ryan J. Geusz & Mei-Lin Okino & Jee Yun Han & Michael Miller & Rebecca Melton & Elisha Beebe & Paola Benaglio & Serina Huang & Katha Korgaonkar & Sandra Heller & Alexander Kleger & Seba, 2021. "Interpreting type 1 diabetes risk with genetics and single-cell epigenomics," Nature, Nature, vol. 594(7863), pages 398-402, June.
    4. Rabab Nasrallah & Charlotte J. Imianowski & Lara Bossini-Castillo & Francis M. Grant & Mikail Dogan & Lindsey Placek & Lina Kozhaya & Paula Kuo & Firas Sadiyah & Sarah K. Whiteside & Maxwell R. Mumbac, 2020. "A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells," Nature, Nature, vol. 583(7816), pages 447-452, July.
    5. Yi Han & Qiong Jia & Pedram Shafiei Jahani & Benjamin P. Hurrell & Calvin Pan & Pin Huang & Janet Gukasyan & Nicholas C. Woodward & Eleazar Eskin & Frank D. Gilliland & Omid Akbari & Jaana A. Hartiala, 2020. "Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    6. Simon H. Jiang & Vicki Athanasopoulos & Julia I. Ellyard & Aaron Chuah & Jean Cappello & Amelia Cook & Savit B. Prabhu & Jacob Cardenas & Jinghua Gu & Maurice Stanley & Jonathan A. Roco & Ilenia Papa , 2019. "Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    7. Andrew D. Grotzinger & Mijke Rhemtulla & Ronald Vlaming & Stuart J. Ritchie & Travis T. Mallard & W. David Hill & Hill F. Ip & Riccardo E. Marioni & Andrew M. McIntosh & Ian J. Deary & Philipp D. Koel, 2019. "Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits," Nature Human Behaviour, Nature, vol. 3(5), pages 513-525, May.
    8. 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.
    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. Matthew T. Patrick & Qinmengge Li & Rachael Wasikowski & Nehal Mehta & Johann E. Gudjonsson & James T. Elder & Xiang Zhou & Lam C. Tsoi, 2022. "Shared genetic risk factors and causal association between psoriasis and coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. 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.
    3. 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.
    4. 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.
    5. Caitlin E. Carey & Rebecca Shafee & Robbee Wedow & Amanda Elliott & Duncan S. Palmer & John Compitello & Masahiro Kanai & Liam Abbott & Patrick Schultz & Konrad J. Karczewski & Samuel C. Bryant & Caro, 2024. "Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation," Nature Human Behaviour, Nature, vol. 8(8), pages 1599-1615, August.
    6. Clara Albiñana & Zhihong Zhu & Nis Borbye-Lorenzen & Sanne Grundvad Boelt & Arieh S. Cohen & Kristin Skogstrand & Naomi R. Wray & Joana A. Revez & Florian Privé & Liselotte V. Petersen & Cynthia M. Bu, 2023. "Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. 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.
    8. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. 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.
    10. Julia Schröder & Vitalia Schüller & Andrea May & Christian Gerges & Mario Anders & Jessica Becker & Timo Hess & Nicole Kreuser & René Thieme & Kerstin U Ludwig & Tania Noder & Marino Venerito & Lothar, 2019. "Identification of loci of functional relevance to Barrett’s esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with gen," PLOS ONE, Public Library of Science, vol. 14(12), pages 1-12, December.
    11. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    12. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    13. Brittany L. Mitchell & Jake R. Saklatvala & Nick Dand & Fiona A. Hagenbeek & Xin Li & Josine L. Min & Laurent Thomas & Meike Bartels & Jouke Hottenga & Michelle K. Lupton & Dorret I. Boomsma & Xianjun, 2022. "Genome-wide association meta-analysis identifies 29 new acne susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    14. Zichen Zhang & Ye Eun Bae & Jonathan R. Bradley & Lang Wu & Chong Wu, 2022. "SUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Wenjie Pan & Xuan Wang & Chunhua Ren & Xiao Jiang & Sanqiang Gong & Zhenyu Xie & Nai-Kei Wong & Xiaomin Li & Jiasheng Huang & Dingding Fan & Peng Luo & Yun Yang & Xinyue Ren & Suzhong Yu & Zhou Qin & , 2024. "Sea cucumbers and their symbiotic microbiome have evolved to feed on seabed sediments," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    16. Zhaotong Lin & Wei Pan, 2024. "A robust cis-Mendelian randomization method with application to drug target discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    17. Alberto Díez-Sánchez & Håvard T. Lindholm & Pia M. Vornewald & Jenny Ostrop & Rouan Yao & Andrew B. Single & Anne Marstad & Naveen Parmar & Tovah N. Shaw & Mara Martín-Alonso & Menno J. Oudhoff, 2024. "LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    18. Yuandan Wei & Jianxin Zhen & Liang Hu & Yuqin Gu & Yanhong Liu & Xinxin Guo & Zijing Yang & Hao Zheng & Shiyao Cheng & Fengxiang Wei & Likuan Xiong & Siyang Liu, 2024. "Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    19. Wang, Chao & Zhan, Jinyan & Wang, Huihui & Yang, Zheng & Chu, Xi & Liu, Wei & Teng, Yanmin & Liu, Huizi & Wang, Yifan, 2022. "Multi-group analysis on the mechanism of residents' low-carbon behaviors in Beijing, China," Technological Forecasting and Social Change, Elsevier, vol. 183(C).
    20. Susanne Kessler & Bradly Burke & Geoffroy Andrieux & Jan Schinköthe & Lea Hamberger & Johannes Kacza & Shijun Zhan & Clara Reasoner & Taru S. Dutt & Maria Kaukab Osman & Marcela Henao-Tamayo & Julian , 2024. "Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:14:y:2023:i:1:d:10.1038_s41467-023-38389-6. 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.