Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes
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.
Authors
- Mariusz Ołtarzewski (ORCID: https://orcid.org/0000-0002-3353-723X)
- Kristina Casteels (ORCID: https://orcid.org/0000-0001-9690-3551)
- Nancy Yu (ORCID: https://orcid.org/0000-0001-8321-8141)
- Olga Kordonouri (ORCID: https://orcid.org/0000-0001-9563-3537)
- Christiane Winkler (ORCID: https://orcid.org/0000-0002-7606-3687)
- Agnese Petrera (ORCID: https://orcid.org/0000-0002-0583-6195)
- Stefanie M. Hauck (ORCID: https://orcid.org/0000-0002-1630-6827)
- Ezio E. Bonifacio (ORCID: https://orcid.org/0000-0002-8704-4713)
- Reinhard Berner (ORCID: https://orcid.org/0000-0002-6216-9173)
- Eleftheria Zeggini (ORCID: https://orcid.org/0000-0003-4238-659X)
- Georgia Katsoula (ORCID: https://orcid.org/0000-0001-9611-9281)
- Konstantinos Hatzikotoulas (ORCID: https://orcid.org/0000-0002-4699-3672)
- Jose Zapardiel‐Gonzalo (ORCID: https://orcid.org/0000-0002-9098-1652)
- Mauro Tutino (ORCID: https://orcid.org/0000-0003-2222-3128)
- Peter Kreitmaier (ORCID: https://orcid.org/0000-0001-7431-4529)
- Helena Elding Larsson (ORCID: https://orcid.org/0000-0003-3306-1742)
- Raffael Ott (ORCID: https://orcid.org/0000-0002-5178-1033)
- Agnieszka Szypowska (ORCID: https://orcid.org/0000-0002-3407-3174)
- Andreas Weiß (ORCID: https://orcid.org/0000-0001-9597-0576)
- Young‐Chan Park (ORCID: https://orcid.org/0000-0001-8964-4571)
- Anette-Gabriele Ziegler
Institutions
- Lund University (SE)
- Medical University of Warsaw (PL)
- TUM Klinikum (DE)
- Center for Environmental Health (US)
- Helmholtz Zentrum München (DE)
- Kinderkrankenhaus auf der Bult (DE)
- Skåne University Hospital (SE)
- University Hospital Carl Gustav Carus (DE)
- Paul Langerhans Institute Dresden (DE)
- Technical University of Munich (DE)
- Technische Universität Dresden (DE)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1038/s41467-025-58972-3
- Citations
- 5
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Bundesministerium für Bildung und Forschung