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

Mauro Tutino, Nancy Yiu-Lin Yu, Konstantinos Hatzikotoulas, Young-Chan Park, Peter Kreitmaier, Georgia Katsoula, Reinhard Berner, Kristina Casteels, Helena Elding Larsson, Olga Kordonouri, Mariusz Ołtarzewski, Agnieszka Szypowska, Raffael Ott, Andreas Weiss, Christiane Winkler, Jose Zapardiel-Gonzalo, Agnese Petrera, Stefanie M. Hauck, Ezio Bonifacio, Anette-Gabriele Ziegler and Eleftheria Zeggini ()
Additional contact information
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
Georgia Katsoula: Helmholtz Zentrum München – German Research Center for Environmental Health
Reinhard Berner: Technische Universität Dresden
Kristina Casteels: University Hospitals Leuven
Helena Elding Larsson: Lund University
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
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
Anette-Gabriele Ziegler: German Research Center for Environmental Health
Eleftheria Zeggini: Helmholtz Zentrum München – German Research Center for Environmental Health

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58972-3

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