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.
Authors
- Ashley Frazer‐Abel
- Bobbie‐Jo Webb‐Robertson (ORCID: https://orcid.org/0000-0002-4744-2397)
- Ani Manichaikul (ORCID: https://orcid.org/0000-0002-5998-795X)
- Thomas Metz (ORCID: https://orcid.org/0000-0001-6049-3968)
- Ernesto Satoshi Nakayasu (ORCID: https://orcid.org/0000-0002-4056-2695)
- Xiaowei Hu (ORCID: https://orcid.org/0000-0001-7804-7392)
- Hemang M. Parikh (ORCID: https://orcid.org/0000-0002-9076-6709)
- Marian Rewers (ORCID: https://orcid.org/0000-0003-3829-9207)
- Stephen S. Rich (ORCID: https://orcid.org/0000-0003-3872-7793)
- Suna Önengüt-Gümüşcü (ORCID: https://orcid.org/0000-0002-6563-8334)
- Wei‐Min Chen (ORCID: https://orcid.org/0000-0002-5247-7826)
Institutions
- Pacific Northwest National Laboratory (US)
- Colorado School of Public Health (US)
- University of South Florida (US)
- University of Virginia (US)
- University of Colorado Anschutz Medical Campus (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1038/s42003-025-08739-9
- Citations
- 1
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- University of Virginia
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Environmental Health Sciences
- National Institute of Child Health and Human Development
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development