IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58972-3.html
   My bibliography  Save this article

Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes

Author

Listed:
  • Mauro Tutino

    (Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Nancy Yiu-Lin Yu

    (Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Konstantinos Hatzikotoulas

    (Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Young-Chan Park

    (Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Peter Kreitmaier

    (Helmholtz Zentrum München – German Research Center for Environmental Health
    Graduate School of Experimental Medicine
    TUM School of Medicine and Health)

  • Georgia Katsoula

    (Helmholtz Zentrum München – German Research Center for Environmental Health
    Graduate School of Experimental Medicine
    TUM School of Medicine and Health)

  • Reinhard Berner

    (Technische Universität Dresden)

  • Kristina Casteels

    (University Hospitals Leuven
    KU Leuven)

  • Helena Elding Larsson

    (Lund University
    Malmö/Lund)

  • Olga Kordonouri

    (Kinder- und Jugendkrankenhaus AUF DER BULT)

  • Mariusz Ołtarzewski

    (Institute of Mother and Child)

  • Agnieszka Szypowska

    (Medical University of Warsaw)

  • Raffael Ott

    (German Research Center for Environmental Health)

  • Andreas Weiss

    (German Research Center for Environmental Health)

  • Christiane Winkler

    (German Research Center for Environmental Health
    Forschergruppe Diabetes e.V. at Helmholtz Munich)

  • Jose Zapardiel-Gonzalo

    (German Research Center for Environmental Health)

  • Agnese Petrera

    (Helmholtz Zentrum München - German Research Center for Environmental Health)

  • Stefanie M. Hauck

    (Helmholtz Zentrum München - German Research Center for Environmental Health)

  • Ezio Bonifacio

    (Technische Universität Dresden
    Technische Universität Dresden)

  • Anette-Gabriele Ziegler

    (German Research Center for Environmental Health
    Forschergruppe Diabetes e.V. at Helmholtz Munich
    Technical University Munich)

  • Eleftheria Zeggini

    (Helmholtz Zentrum München – German Research Center for Environmental Health
    TUM School of Medicine and Health)

Abstract

Type 1 diabetes is a chronic, autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. Early detection can facilitate timely intervention, potentially delaying or preventing disease onset. Circulating proteins reflect dysregulated biological processes and offer insights into early disease mechanisms. Here, we construct a genome-wide pQTL map of 1985 proteins in 695 newborn babies (median age 2 days) at increased genetic risk of developing Type 1 diabetes. We identify 535 pQTLs (352 cis-pQTLs, 183 trans-pQTLs), 62 of which characteristic of newborns. We show colocalization of pQTLs for CTRB1, APOBR, IL7R, CPA1, and PNLIPRP1 with Type 1 diabetes GWAS signals, and Mendelian randomization causally implicates each of these five proteins in the aetiology of Type 1 diabetes. Our study illustrates the utility of newborn molecular profiles for discovering potential drug targets for childhood diseases of significant concern.

Suggested Citation

  • Mauro Tutino & Nancy Yiu-Lin Yu & Konstantinos Hatzikotoulas & Young-Chan Park & Peter Kreitmaier & Georgia Katsoula & Reinhard Berner & Kristina Casteels & Helena Elding Larsson & Olga Kordonouri & M, 2025. "Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58972-3
    DOI: 10.1038/s41467-025-58972-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58972-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58972-3?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. 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.
    2. 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.
    3. Grimur Hjorleifsson Eldjarn & Egil Ferkingstad & Sigrun H. Lund & Hannes Helgason & Olafur Th. Magnusson & Kristbjorg Gunnarsdottir & Thorunn A. Olafsdottir & Bjarni V. Halldorsson & Pall I. Olason & , 2023. "Large-scale plasma proteomics comparisons through genetics and disease associations," Nature, Nature, vol. 622(7982), pages 348-358, October.
    4. Alexander Gudjonsson & Valborg Gudmundsdottir & Gisli T. Axelsson & Elias F. Gudmundsson & Brynjolfur G. Jonsson & Lenore J. Launer & John R. Lamb & Lori L. Jennings & Thor Aspelund & Valur Emilsson &, 2022. "A genome-wide association study of serum proteins reveals shared loci with common diseases," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Benjamin B. Sun & Joshua Chiou & Matthew Traylor & Christian Benner & Yi-Hsiang Hsu & Tom G. Richardson & Praveen Surendran & Anubha Mahajan & Chloe Robins & Steven G. Vasquez-Grinnell & Liping Hou & , 2023. "Plasma proteomic associations with genetics and health in the UK Biobank," Nature, Nature, vol. 622(7982), pages 329-338, October.
    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. Baihan Wang & Alfred Pozarickij & Mohsen Mazidi & Neil Wright & Pang Yao & Saredo Said & Andri Iona & Christiana Kartsonaki & Hannah Fry & Kuang Lin & Yiping Chen & Huaidong Du & Daniel Avery & Dan Sc, 2025. "Comparative studies of 2168 plasma proteins measured by two affinity-based platforms in 4000 Chinese adults," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    2. Yijun Li & Zhaozhong Zhu & Carlos A. Camargo & Janice A. Espinola & Kohei Hasegawa & Liming Liang, 2025. "Epigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in infants," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    3. Anders Mälarstig & Felix Grassmann & Leo Dahl & Marios Dimitriou & Dianna McLeod & Marike Gabrielson & Karl Smith-Byrne & Cecilia E. Thomas & Tzu-Hsuan Huang & Simon K. G. Forsberg & Per Eriksson & Mi, 2023. "Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    4. Chirag Krishna & Joshua Chiou & Saori Sakaue & Joyce B. Kang & Stephen M. Christensen & Isac Lee & Melis Atalar Aksit & Hye In Kim & David Schack & Soumya Raychaudhuri & Daniel Ziemek & Xinli Hu, 2024. "The influence of HLA genetic variation on plasma protein expression," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Karsten Suhre & Guhan Ram Venkataraman & Harendra Guturu & Anna Halama & Nisha Stephan & Gaurav Thareja & Hina Sarwath & Khatereh Motamedchaboki & Margaret K. R. Donovan & Asim Siddiqui & Serafim Batz, 2024. "Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Douglas P. Loesch & Manik Garg & Dorota Matelska & Dimitrios Vitsios & Xiao Jiang & Scott C. Ritchie & Benjamin B. Sun & Heiko Runz & Christopher D. Whelan & Rury R. Holman & Robert J. Mentz & Filipe , 2025. "Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    7. Xuening Zhang & Hao Zhao & Meng Wan & Jinyu Man & Tongchao Zhang & Xiaorong Yang & Ming Lu, 2025. "Associations of 2923 plasma proteins with incident inflammatory bowel disease in a prospective cohort study and genetic analysis," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    8. 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.
    9. 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.
    10. Yash Patel & Jean Shin & Eeva Sliz & Ariana Tang & Aniket Mishra & Rui Xia & Edith Hofer & Hema Sekhar Reddy Rajula & Ruiqi Wang & Frauke Beyer & Katrin Horn & Max Riedl & Jing Yu & Henry Völzke & Rob, 2024. "Genetic risk factors underlying white matter hyperintensities and cortical atrophy," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    11. Jing Sun & Yue Liu & Jianhui Zhao & Bin Lu & Siyun Zhou & Wei Lu & Jingsun Wei & Yeting Hu & Xiangxing Kong & Junshun Gao & Hong Guan & Junli Gao & Qian Xiao & Xue Li, 2024. "Plasma proteomic and polygenic profiling improve risk stratification and personalized screening for colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    12. Naman S. Shetty & Mokshad Gaonkar & Nirav Patel & Akhil Pampana & Nehal Vekariya & Peng Li & Garima Arora & Pankaj Arora, 2024. "Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants," Nature Communications, Nature, vol. 15(1), pages 1-7, December.
    13. Paul M. H. Tran & Fran Dong & Eileen Kim & Katherine P. Richardson & Lynn K. H. Tran & Kathleen Waugh & Diane Hopkins & Richard D. Cummings & Peng George Wang & Marian J. Rewers & Jin-Xiong She & Shar, 2022. "Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    14. Jakub Kopal & Kuldeep Kumar & Kimia Shafighi & Karin Saltoun & Claudia Modenato & Clara A. Moreau & Guillaume Huguet & Martineau Jean-Louis & Charles-Olivier Martin & Zohra Saci & Nadine Younis & Elis, 2024. "Using rare genetic mutations to revisit structural brain asymmetry," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    15. Erik Duijvelaar & Jack Gisby & James E. Peters & Harm Jan Bogaard & Jurjan Aman, 2024. "Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Yuji Yamamoto & Yuya Shirai & Kyuto Sonehara & Shinichi Namba & Takafumi Ojima & Kenichi Yamamoto & Ryuya Edahiro & Ken Suzuki & Akinori Kanai & Yoshiya Oda & Yutaka Suzuki & Takayuki Morisaki & Akira, 2025. "Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    17. Chachrit Khunsriraksakul & Qinmengge Li & Havell Markus & Matthew T. Patrick & Renan Sauteraud & Daniel McGuire & Xingyan Wang & Chen Wang & Lida Wang & Siyuan Chen & Ganesh Shenoy & Bingshan Li & Xue, 2023. "Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Abolfazl Doostparast Torshizi & Dongnhu T. Truong & Liping Hou & Bart Smets & Christopher D. Whelan & Shuwei Li, 2024. "Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson’s disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Hongru Li & Jingyi Zhao & Jinglan Dai & Dongfang You & Yang Zhao & David C. Christiani & Feng Chen & Sipeng Shen, 2025. "Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    20. Parker C. Wilson & Yoshiharu Muto & Haojia Wu & Anil Karihaloo & Sushrut S. Waikar & Benjamin D. Humphreys, 2022. "Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression," Nature Communications, Nature, vol. 13(1), pages 1-20, 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:16:y:2025:i:1:d:10.1038_s41467-025-58972-3. 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.