{"doi":"10.1101/2025.05.26.25328184","title":"A case-cohort longitudinal study for the analysis of microbial associations and viruses on the risk of celiac disease (MAVRiC)","abstract":"Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten before a child can develop the chronic autoimmune disorder. However, these factors alone are not sufficient. Even a child with persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity (CDA), does not necessarily develop celiac disease. Larger longitudinal studies are needed to determine the impact of time-varying infections and gut microorganisms on the subsequent and specific risk of celiac disease. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. Following the TEDDY cohort up age 3-years, CDA was confirmed in 704 of the 6132 genetically at-risk children. Celiac disease onset was defined as the age CDA developed when followed by a biopsy-proven diagnosis. A competing risk analysis was performed on celiac disease onset cases (CD-onset) as well as CDA children with no diagnosis (CDA-only) and results show genetic factors (additional HLA-DR3-DQ2 haplotype, higher non-HLA polygenic risk score, sex-girl) and a more rapid increase in gluten-consumption correlate with significant increased risk of both outcomes. However, reports of virus-related respiratory infections in August to October during follow-up correlated with an increased risk of a CD-onset but not with CDA-only. To create a case-cohort study, a sub-cohort of 561 children (9% sampling fraction) was first randomly selected to represent the TEDDY cohort over time while at risk of CDA. It included 483 children followed until age 3-years and 78 children followed before developing CDA (CDA-only n=41/78, CD-onset n=37/78). All incident CD-onset children (N=306) were included to form the case group. This case-cohort will be utilized to analyze virus antibodies and bacteriome from longitudinal plasma and stool samples (the Microbial Associations and Viruses on the Risk of Celiac disease study, MAVRiC).","journal":"medRxiv","year":2025,"id":566803,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9416,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363713,"name":"Eric W. Triplett","orcid":"0000-0002-1845-4866","position":1,"is_corresponding":false},{"id":95838,"name":"Heikki Hyöty","orcid":"0000-0003-0370-4145","position":2,"is_corresponding":false},{"id":1470758,"name":"Angelica P. Ahrens","orcid":"0000-0002-1478-7559","position":3,"is_corresponding":false},{"id":678206,"name":"Jutta E. Laiho","orcid":"0000-0002-5443-4651","position":4,"is_corresponding":false},{"id":19859,"name":"Joseph F. Petrosino","orcid":"0000-0002-4046-6898","position":5,"is_corresponding":false},{"id":95826,"name":"Richard E. Lloyd","orcid":"0000-0002-6550-3237","position":6,"is_corresponding":false},{"id":703785,"name":"Daniel Agardh","orcid":"0000-0003-1435-1234","position":7,"is_corresponding":false},{"id":703787,"name":"Kristian Lynch","orcid":"0000-0002-4310-4163","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T02:56:40.491968Z","pmid":"40492061","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":[]}