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We performed whole-exome sequencing in a cohort of 107 cases with CeD and 117 unaffected relatives from 66 families. We assessed fourteen HLA-DQ genotypes, based on combinations of four risk haplotypes. Our cohort was predominantly of European ancestry (87%). Compared with at-risk controls, CeD cases showed a significant enrichment of high-risk (22.4 vs. 10.3%) and moderate-risk (64.4 vs. 35.9%) HLA-DQ genotypes. Stratification based on the weighted impact of fourteen HLA-DQ genotypes yields a more accurate risk assessment than assuming equal contributions from four risk haplotypes. The HLA-B*08:01 allele was more frequent in CeD patients than in controls (32.2 vs. 16.7%). Among individuals of European ancestry, the AH8.1 long haplotype was present in 62% of cases vs. 49% of controls. Whole-exome sequencing enables stratification of first-degree relatives into discrete risk categories, identifying 10% as high risk and \u223c50% as having negligible genetic risk.<\/jats:p>","DOI":"10.70962\/jhi.20260051","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:21:52Z","timestamp":1786688512000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["The clinical utility of exome sequencing for risk stratification in celiac disease"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7607-9005","authenticated-orcid":true,"given":"Talha","family":"Asif","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Texas Southwestern Medical Center 1 Division of Digestive and Liver Diseases, Department of Internal Medicine, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5504-0378","authenticated-orcid":true,"given":"Michele","family":"Akalay","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Texas Southwestern Medical Center 2 Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-5685","authenticated-orcid":true,"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00dvg7y05","id-type":"ROR","asserted-by":"publisher"}],"name":"Harvard Medical School, Boston Children\u2019s Hospital 4 Department of Pediatrics, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-9634","authenticated-orcid":true,"given":"Peter H.R.","family":"Green","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01esghr10","id-type":"ROR","asserted-by":"publisher"}],"name":"Celiac Disease Center, Columbia University 3 , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9983-2373","authenticated-orcid":true,"given":"Xiao-Fei","family":"Kong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Texas Southwestern Medical Center 1 Division of Digestive and Liver Diseases, Department of Internal Medicine, , Dallas, TX,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center 5 , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"2026090109003086800_bib1","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cgh.2017.06.037","article-title":"Global Prevalence of Celiac Disease: Systematic review and meta-analysis","volume":"16","author":"Singh","year":"2018","journal-title":"Clin. 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