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Human leukocyte antigen (HLA) DQ gene testing is available in clinic but does not include non\u2010HLA attributed risk and is limited by discrete risk stratification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To accurately characterise both HLA and non\u2010HLA coeliac disease genetic risk as a single nucleotide polymorphism\u2013based GRS and evaluate diagnostic utility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a 42 single nucleotide polymorphism coeliac disease GRS from a European case\u2010control study (12\u00a0041 cases vs 12\u00a0228 controls) using HLA\u2010DQ imputation and published genome\u2010wide 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The GRS was more discriminative of coeliac disease than HLA\u2010DQ stratification in UK Biobank (receiver operating characteristic area under the curve [ROC\u2010AUC]\u00a0=\u00a00.88 [95% CIs: 0.87\u20100.89] vs 0.82 [95% CIs: 0.80\u20100.83]). We demonstrated similar discrimination in the pilot clinical cohort (114 cases vs 40 controls, ROC\u2010AUC\u00a0=\u00a00.84 [95% CIs: 0.76\u20100.91]). As a rule\u2010out test, no children with coeliac disease in the clinical cohort had a GRS below 38th population centile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A single nucleotide polymorphism\u2013based GRS may offer more effective and cost\u2010efficient testing of coeliac disease genetic risk in comparison to HLA\u2010DQ stratification. As a comparatively inexpensive test it could facilitate non\u2010invasive coeliac disease diagnosis but needs detailed assessment in the context of other diagnostic tests and against current diagnostic algorithms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15826","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T15:07:50Z","timestamp":1597331270000},"page":"1165-1173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0607-9990","authenticated-orcid":false,"given":"Seth A.","family":"Sharp","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-922X","authenticated-orcid":false,"given":"Samuel E.","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science University of Exeter Medical School Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Kimmitt","sequence":"additional","affiliation":[{"name":"Royal Devon &amp; 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