Genetic mapping of complement system proteins for islet autoimmunity in children with high risk of T1D.

Recent studies have reported the involvement of complement system proteins in the initiation and progression of islet autoimmunity (IA) in the study of Type 1 diabetes (T1D). However, the genetic factors of complement system proteins at the time of triggering of IA are unknown. Through complement system protein quantitative trait locus (pQTL) mapping discovery analysis of 170 participants from the Diabetes Autoimmunity Study in the Young (DAISY) and replication analysis of 385 IA cases from The Environment Determinants of Diabetes in the Young (TEDDY) study, we identify 68 significant pQTLs in total for C8A, C8B, CFB, C4A, and MBL2. Furthermore, all replicated pQTLs of CFB and C4A are previously reported to be associated with T1D risk. Our study provides evidence for the potential biological roles of complement system proteins in the etiology of IA and T1D for young children at high risk of developing T1D.