Population screening of adults identifies novel genetic variants associated with celiac disease

• Published in: SCIENTIFIC REPORTS Vol. 15; no. 1; pp. 19764 - 13
• Main Authors: Alam, Mohammad Sayeef, Thomas, Laurent, Brumpton, Ben, Hveem, Kristian, Lundin, Knut E. A., Withoff, Sebo, Jonkers, Iris H., Sollid, Ludvig M., Hjort, Rebecka, Ness-Jensen, Eivind
• Format: Journal Article Publication
• Language: English
• Published: London Nature Publishing Group UK 05.06.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205; 631/208/212; 631/208/721; 692/4020/1503/1581/1357; Adult; Antigens; Autoimmune; Autoimmune diseases; Biobanks; Celiac; Celiac disease; Celiac Disease - diagnosis; Celiac Disease - epidemiology; Celiac Disease - genetics; Chromosome 5; Female; Genes; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Genotyping; Gluten; GWAS; Haplotypes; Heritability; Histocompatibility antigen HLA; Hospitals; Humanities and Social Sciences; Humans; Leukocytes; Male; Medical screening; Medicine; Middle Aged; multidisciplinary; Non-HLA; Polymorphism, Single Nucleotide; Quality control; Response rates; Rheumatoid arthritis; RNA, Long Noncoding - genetics; Science; Science (multidisciplinary); Serology; Autoimmune; GWAS; Gluten; Non-HLA; Celiac
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-04421-6

Celiac disease (CeD) is an autoimmune disease driven by a complex genetic interplay within and beyond the human leukocyte antigen (HLA) region. Despite this, half of its heritability remains unexplained, with most of the unidentified variants located in non-protein coding regions. Here we performed a genome-wide association study among 52,342 adults screened for CeD, including 465 previously undiagnosed and 361 already diagnosed cases, which mitigated the likely disease misclassification present in previous studies. Genotyping and imputation yielded approximately 24.9 million variants for analysis. The study identified 15 novel associations ( P  < 5E-08) in 12 loci in addition to all the previously associated loci at lower significance thresholds ( P  < 5E-03). The 5p15.33 locus in the long non-coding RNA gene ( LINC01019 ) showed the highest potential for a true association with CeD. Notably, variants in 5p15.33 has also been associated with rheumatoid arthritis, suggesting a new shared autoimmune locus.