Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes
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 processe...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58972-3 |
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| author | 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 Eleftheria Zeggini |
| author_facet | 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 Eleftheria Zeggini |
| author_sort | Mauro Tutino |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-da37bbc2b763499e8bf78c89325d4cce |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da37bbc2b763499e8bf78c89325d4cce2025-08-20T02:28:41ZengNature PortfolioNature Communications2041-17232025-04-011611910.1038/s41467-025-58972-3Genetics of circulating proteins in newborn babies at high risk of type 1 diabetesMauro Tutino0Nancy Yiu-Lin Yu1Konstantinos Hatzikotoulas2Young-Chan Park3Peter Kreitmaier4Georgia Katsoula5Reinhard Berner6Kristina Casteels7Helena Elding Larsson8Olga Kordonouri9Mariusz Ołtarzewski10Agnieszka Szypowska11Raffael Ott12Andreas Weiss13Christiane Winkler14Jose Zapardiel-Gonzalo15Agnese Petrera16Stefanie M. Hauck17Ezio Bonifacio18Anette-Gabriele Ziegler19Eleftheria Zeggini20Institute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthDepartment of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Pediatrics, University Hospitals LeuvenUnit for Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund UniversityKinder- und Jugendkrankenhaus AUF DER BULTDepartment of Screening and Metabolic Diagnostics, Institute of Mother and ChildDepartment of Paediatric Diabetology and Paediatrics, Medical University of WarsawInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental HealthInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental HealthInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental HealthInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental HealthMetabolomics and Proteomics Core, Helmholtz Zentrum München - German Research Center for Environmental HealthMetabolomics and Proteomics Core, Helmholtz Zentrum München - German Research Center for Environmental HealthCenter for Regenerative Therapies Dresden, Technische Universität DresdenInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental HealthInstitute of Translational Genomics, Helmholtz Zentrum München – German Research Center for Environmental HealthAbstract 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.https://doi.org/10.1038/s41467-025-58972-3 |
| spellingShingle | 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 Eleftheria Zeggini Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes Nature Communications |
| title | Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes |
| title_full | Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes |
| title_fullStr | Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes |
| title_full_unstemmed | Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes |
| title_short | Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes |
| title_sort | genetics of circulating proteins in newborn babies at high risk of type 1 diabetes |
| url | https://doi.org/10.1038/s41467-025-58972-3 |
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