IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45445-2.html
   My bibliography  Save this article

Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants

Author

Listed:
  • Xin Han

    (Sichuan University
    West China Hospital, Sichuan University
    Sichuan University)

  • Qing Shen

    (Tongji University School of Medicine
    Tongji University
    Karolinska Institutet)

  • Can Hou

    (West China Hospital, Sichuan University
    Sichuan University)

  • Huazhen Yang

    (West China Hospital, Sichuan University
    Sichuan University)

  • Wenwen Chen

    (West China Hospital, Sichuan University
    Sichuan University)

  • Yu Zeng

    (West China Hospital, Sichuan University
    Sichuan University)

  • Yuanyuan Qu

    (West China Hospital, Sichuan University
    Sichuan University)

  • Chen Suo

    (Fudan University
    Fudan University)

  • Weimin Ye

    (Karolinska Institutet)

  • Fang Fang

    (Karolinska Institutet)

  • Unnur A. Valdimarsdóttir

    (Karolinska Institutet
    University of Iceland
    Harvard T H Chan School of Public Health)

  • Huan Song

    (West China Hospital, Sichuan University
    Sichuan University
    University of Iceland)

Abstract

Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Suggested Citation

  • Xin Han & Qing Shen & Can Hou & Huazhen Yang & Wenwen Chen & Yu Zeng & Yuanyuan Qu & Chen Suo & Weimin Ye & Fang Fang & Unnur A. Valdimarsdóttir & Huan Song, 2024. "Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45445-2
    DOI: 10.1038/s41467-024-45445-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45445-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-45445-2?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. Troels Siggaard & Roc Reguant & Isabella F. Jørgensen & Amalie D. Haue & Mette Lademann & Alejandro Aguayo-Orozco & Jessica X. Hjaltelin & Anders Boeck Jensen & Karina Banasik & Søren Brunak, 2020. "Disease trajectory browser for exploring temporal, population-wide disease progression patterns in 7.2 million Danish patients," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    2. ., 2012. "Clinically Integrated Health Care in the English NHS," Chapters, in: Health Care, the Market and Consumer Choice, chapter 15, pages 214-216, Edward Elgar Publishing.
    3. Anders Boeck Jensen & Pope L. Moseley & Tudor I. Oprea & Sabrina Gade Ellesøe & Robert Eriksson & Henriette Schmock & Peter Bjødstrup Jensen & Lars Juhl Jensen & Søren Brunak, 2014. "Temporal disease trajectories condensed from population-wide registry data covering 6.2 million patients," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    4. 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.
    5. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    6. Roy, S.S. & Foraker, R.E. & Girton, R.A. & Mansfield, A.J., 2015. "Posttraumatic stress disorder and incident heart failure among a community-based sample of US veterans," American Journal of Public Health, American Public Health Association, vol. 105(4), pages 757-763.
    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. Xiangwei Li & Thomas Delerue & Ben Schöttker & Bernd Holleczek & Eva Grill & Annette Peters & Melanie Waldenberger & Barbara Thorand & Hermann Brenner, 2022. "Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Ahrum Son & Hyunsoo Kim & Jolene K. Diedrich & Casimir Bamberger & Daniel B. McClatchy & Stuart A. Lipton & John R. Yates, 2024. "Using in vivo intact structure for system-wide quantitative analysis of changes in proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Shahram Bahrami & Kaja Nordengen & Jaroslav Rokicki & Alexey A. Shadrin & Zillur Rahman & Olav B. Smeland & Piotr P. Jaholkowski & Nadine Parker & Pravesh Parekh & Kevin S. O’Connell & Torbjørn Elvsås, 2024. "The genetic landscape of basal ganglia and implications for common brain disorders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Jialiang S. Wang & Tushar Kamath & Courtney M. Mazur & Fatemeh Mirzamohammadi & Daniel Rotter & Hironori Hojo & Christian D. Castro & Nicha Tokavanich & Rushi Patel & Nicolas Govea & Tetsuya Enishi & , 2021. "Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    7. Bhuwan Khatri & Kandice L. Tessneer & Astrid Rasmussen & Farhang Aghakhanian & Tove Ragna Reksten & Adam Adler & Ilias Alevizos & Juan-Manuel Anaya & Lara A. Aqrawi & Eva Baecklund & Johan G. Brun & S, 2022. "Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Ryan J. Geusz & Allen Wang & Dieter K. Lam & Nicholas K. Vinckier & Konstantinos-Dionysios Alysandratos & David A. Roberts & Jinzhao Wang & Samy Kefalopoulou & Araceli Ramirez & Yunjiang Qiu & Joshua , 2021. "Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    9. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Aftab Nadeem & Athar Alam & Eric Toh & Si Lhyam Myint & Zia ur Rehman & Tao Liu & Marta Bally & Anna Arnqvist & Hui Wang & Jun Zhu & Karina Persson & Bernt Eric Uhlin & Sun Nyunt Wai, 2021. "Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA," PLOS Pathogens, Public Library of Science, vol. 17(3), pages 1-34, March.
    12. Hao A. Duong & Kenkichi Baba & Jason P. DeBruyne & Alec J. Davidson & Christopher Ehlen & Michael Powell & Gianluca Tosini, 2024. "Environmental circadian disruption re-writes liver circadian proteomes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Xuelong Yao & Zongyang Lu & Zhanying Feng & Lei Gao & Xin Zhou & Min Li & Suijuan Zhong & Qian Wu & Zhenbo Liu & Haofeng Zhang & Zeyuan Liu & Lizhi Yi & Tao Zhou & Xudong Zhao & Jun Zhang & Yong Wang , 2022. "Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    15. Paul R. H. J. Timmers & James F. Wilson & Peter K. Joshi & Joris Deelen, 2020. "Multivariate genomic scan implicates novel loci and haem metabolism in human ageing," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    16. Zhen Qiao & Julia Sidorenko & Joana A. Revez & Angli Xue & Xueling Lu & Katri Pärna & Harold Snieder & Peter M. Visscher & Naomi R. Wray & Loic Yengo, 2023. "Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    17. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    19. Mijeong Kim & Yu Jin Jang & Muyoung Lee & Qingqing Guo & Albert J. Son & Nikita A. Kakkad & Abigail B. Roland & Bum-Kyu Lee & Jonghwan Kim, 2024. "The transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Alejandro Gomez Toledo & Eleni Bratanis & Erika Velásquez & Sounak Chowdhury & Berit Olofsson & James T. Sorrentino & Christofer Karlsson & Nathan E. Lewis & Jeffrey D. Esko & Mattias Collin & Oonagh , 2023. "Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections," Nature Communications, Nature, vol. 14(1), pages 1-16, 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:15:y:2024:i:1:d:10.1038_s41467-024-45445-2. 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.