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. 2025 Sep 26;8(1):1366.
doi: 10.1038/s42003-025-08739-9.

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

Xiaowei Hu  1 , Bobbie-Jo M Webb-Robertson  2   3 , Hemang M Parikh  4 , Ernesto S Nakayasu  2 , Suna Onengut-Gumuscu  5 , Wei-Min Chen  5 , Ashley Frazer-Abel  6 , Thomas O Metz  2 , Stephen S Rich  5 , Marian J Rewers #  7 , Ani Manichaikul #  8
Affiliations

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

Xiaowei Hu et al. Commun Biol. .

Abstract

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Dr. Ani Manichaikul is an Editorial Board Member for Communications Biology, but was not involved in the editorial review of, nor the decision to publish this article.

Figures

Fig. 1
Fig. 1. PheWAS of CFB top replicated cis-pQTL rs150978802.
PheWAS results were obtained from T1D Knowledge Portal (https://t1d.hugeamp.org); the phenotypes in the Figure are sorted by the association p-value between the variant and the phenotype. The Figure shows the top 25 associations out of 232 phenotypes; Beta, effect size of association between rs150978802 and phenotype; error bar indicates 95% confidence interval.
Fig. 2
Fig. 2. PheWAS look-up of C4A top replicated cis-pQTL rs9263822.
PheWAS results were obtained from T1D Knowledge Portal (https://t1d.hugeamp.org); the phenotypes in the Figure are sorted by the association p-value between the variant and the phenotype. The Figure shows the top 25 associations out of 202 phenotypes; Beta, the effect size of the association between rs9263822 and phenotype. The error bar indicates a 95% confidence interval.
See this image and copyright information in PMC

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References

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