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
Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Technical University of Munich, TUM School of Medicine and Health, Graduate School of Experimental Medicine, Munich, Germany.
Nat Commun. 2025 Apr 22;16(1):3750. doi: 10.1038/s41467-025-58972-3.
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.
1型糖尿病是一种慢性自身免疫性疾病，其特征是胰腺中产生胰岛素的β细胞被破坏。早期检测有助于及时干预，可能延迟或预防疾病发作。循环蛋白反映了失调的生物过程，并为早期疾病机制提供了见解。在这里，我们构建了695名有患1型糖尿病遗传风险的新生儿（中位年龄2天）中1985种蛋白质的全基因组pQTL图谱。我们鉴定出535个pQTL（352个顺式pQTL，183个反式pQTL），其中62个是新生儿特有的。我们展示了CTRB1、APOBR、IL7R、CPA1和PNLIPRP1的pQTL与1型糖尿病全基因组关联研究信号的共定位，孟德尔随机化因果推断这五种蛋白质中的每一种都与1型糖尿病的病因有关。我们的研究说明了新生儿分子谱在发现重大儿童疾病潜在药物靶点方面的实用性。
