Nature communications · 2025
Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes.
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Tutino Mauro, Yu Nancy Yiu-Lin, Hatzikotoulas Konstantinos, Park Young-Chan, Kreitmaier Peter, Katsoula Georgia, Berner Reinhard, Casteels Kristina, Elding Larsson Helena, Kordonouri Olga, Ołtarzewski Mariusz, Szypowska Agnieszka, Ott Raffael, Weiss Andreas, Winkler Christiane, Zapardiel-Gonzalo Jose, Petrera Agnese, Hauck Stefanie M, Bonifacio Ezio, Ziegler Anette-Gabriele, Zeggini Eleftheria
Аннотация
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.