Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes
(2025) In Nature Communications 16. p.1-9- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2025-04-22
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 16
- article number
- 3750
- pages
- 1 - 9
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:105003131364
- pmid:40263317
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-025-58972-3
- language
- English
- LU publication?
- yes
- additional info
- © 2025. The Author(s).
- id
- da590954-efe1-4dd5-a980-6aaedf250ba7
- date added to LUP
- 2025-04-23 10:32:45
- date last changed
- 2025-06-05 04:37:40
@article{da590954-efe1-4dd5-a980-6aaedf250ba7, abstract = {{<p>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.</p>}}, author = {{Tutino, Mauro and Yu, Nancy Yiu-Lin and Hatzikotoulas, Konstantinos and Park, Young-Chan and Kreitmaier, Peter and Katsoula, Georgia and Berner, Reinhard and Casteels, Kristina and Elding Larsson, Helena and Kordonouri, Olga and Ołtarzewski, Mariusz and Szypowska, Agnieszka and Ott, Raffael and Weiss, Andreas and Winkler, Christiane and Zapardiel-Gonzalo, Jose and Petrera, Agnese and Hauck, Stefanie M and Bonifacio, Ezio and Ziegler, Anette-Gabriele and Zeggini, Eleftheria}}, issn = {{2041-1723}}, language = {{eng}}, month = {{04}}, pages = {{1--9}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes}}, url = {{http://dx.doi.org/10.1038/s41467-025-58972-3}}, doi = {{10.1038/s41467-025-58972-3}}, volume = {{16}}, year = {{2025}}, }