{"doi":"10.1111/apt.15826","title":"A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care","abstract":"BACKGROUND: Single nucleotide polymorphism-based genetic risk scores (GRS) model genetic risk as a continuum and can discriminate coeliac disease but have not been validated in clinic. Human leukocyte antigen (HLA) DQ gene testing is available in clinic but does not include non-HLA attributed risk and is limited by discrete risk stratification. AIMS: To accurately characterise both HLA and non-HLA coeliac disease genetic risk as a single nucleotide polymorphism-based GRS and evaluate diagnostic utility. METHODS: We developed a 42 single nucleotide polymorphism coeliac disease GRS from a European case-control study (12 041 cases vs 12 228 controls) using HLA-DQ imputation and published genome-wide association studies. We validated the GRS in UK Biobank (1237 cases) and developed direct genotyping assays. We tested the coeliac disease GRS in a pilot clinical cohort of 128 children presenting with suspected coeliac disease. RESULTS: The GRS was more discriminative of coeliac disease than HLA-DQ stratification in UK Biobank (receiver operating characteristic area under the curve [ROC-AUC] = 0.88 [95% CIs: 0.87-0.89] vs 0.82 [95% CIs: 0.80-0.83]). We demonstrated similar discrimination in the pilot clinical cohort (114 cases vs 40 controls, ROC-AUC = 0.84 [95% CIs: 0.76-0.91]). As a rule-out test, no children with coeliac disease in the clinical cohort had a GRS below 38th population centile. CONCLUSIONS: A single nucleotide polymorphism-based GRS may offer more effective and cost-efficient testing of coeliac disease genetic risk in comparison to HLA-DQ stratification. As a comparatively inexpensive test it could facilitate non-invasive coeliac disease diagnosis but needs detailed assessment in the context of other diagnostic tests and against current diagnostic algorithms.","journal":"Alimentary Pharmacology & Therapeutics","year":2020,"id":101729,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":497603,"name":"Samuel E. Jones","orcid":"0000-0003-0153-922X","position":1,"is_corresponding":false},{"id":498468,"name":"Robert Kimmitt","orcid":null,"position":2,"is_corresponding":false},{"id":22004,"name":"Michael N. Weedon","orcid":"0000-0002-6174-6135","position":3,"is_corresponding":false},{"id":497604,"name":"Anne Halpin","orcid":"0000-0001-7475-9245","position":4,"is_corresponding":false},{"id":345045,"name":"Andrew R. Wood","orcid":"0000-0003-1726-948X","position":5,"is_corresponding":false},{"id":241472,"name":"Robin N. Beaumont","orcid":"0000-0003-0750-8248","position":6,"is_corresponding":false},{"id":498469,"name":"Seema King","orcid":null,"position":7,"is_corresponding":false},{"id":64572,"name":"David A. van Heel","orcid":"0000-0002-0637-2265","position":8,"is_corresponding":false},{"id":497605,"name":"Patricia Campbell","orcid":"0000-0002-1909-4807","position":9,"is_corresponding":false},{"id":95829,"name":"William Hagopian","orcid":"0000-0003-2979-0475","position":10,"is_corresponding":false},{"id":497606,"name":"Justine Turner","orcid":"0000-0002-3517-636X","position":11,"is_corresponding":false},{"id":249639,"name":"Richard A. Oram","orcid":"0000-0003-3581-8980","position":12,"is_corresponding":false},{"id":497602,"name":"Seth A. Sharp","orcid":"0000-0002-0607-9990","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-18T22:40:22.678835Z","pmid":"32790217","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":[]}