{"doi":"10.2337/db15-1308","title":"Expression-Based Genome-Wide Association Study Links Vitamin D–Binding Protein With Autoantigenicity in Type 1 Diabetes","abstract":"Type 1 diabetes (T1D) is caused by autoreactive T cells that recognize pancreatic islet antigens and destroy insulin-producing β-cells. This attack results from a breakdown in tolerance for self-antigens, which is controlled by ectopic antigen expression in the thymus and pancreatic lymph nodes (PLNs). The autoantigens known to be involved include a set of islet proteins, such as insulin, GAD65, IA-2, and ZnT8. In an attempt to identify additional antigenic proteins, we performed an expression-based genome-wide association study using microarray data from 118 arrays of the thymus and PLNs of T1D mice. We ranked all 16,089 protein-coding genes by the likelihood of finding repeated differential expression and the degree of tissue specificity for pancreatic islets. The top autoantigen candidate was vitamin D-binding protein (VDBP). T-cell proliferation assays showed stronger T-cell reactivity to VDBP compared with control stimulations. Higher levels and frequencies of serum anti-VDBP autoantibodies (VDBP-Abs) were identified in patients with T1D (n = 331) than in healthy control subjects (n = 77). Serum vitamin D levels were negatively correlated with VDBP-Ab levels in patients in whom T1D developed during the winter. Immunohistochemical localization revealed that VDBP was specifically expressed in α-cells of pancreatic islets. We propose that VDBP could be an autoantigen in T1D.","journal":"Diabetes","year":2016,"id":3977,"datarank":1.392093067634581,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.8504553807379472,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.8504553807379472,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":34,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0502,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2016-03-16","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":39942,"name":"Zhiyuan Zhao","orcid":null,"position":1,"is_corresponding":false},{"id":21639,"name":"Kyoko Toda","orcid":"0000-0002-5919-0182","position":2,"is_corresponding":false},{"id":39943,"name":"Linda Yip","orcid":"0000-0002-6459-2063","position":3,"is_corresponding":false},{"id":39944,"name":"Rebecca Fuhlbrigge","orcid":"0000-0003-0920-5128","position":4,"is_corresponding":false},{"id":39945,"name":"Dongmei Miao","orcid":null,"position":5,"is_corresponding":false},{"id":39946,"name":"C. Garrison Fathman","orcid":"0000-0002-7534-1497","position":6,"is_corresponding":false},{"id":21640,"name":"Satoru Yamada","orcid":"0000-0002-1627-305X","position":7,"is_corresponding":false},{"id":51,"name":"Atul Janardhan Butte","orcid":"0000-0002-7433-2740","position":8,"is_corresponding":false},{"id":39947,"name":"Liping Yu","orcid":"0000-0003-0664-2154","position":9,"is_corresponding":false},{"id":834,"name":"Keiichi Kodama","orcid":"0000-0001-8509-1199","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}