Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants. Issue 3 (23rd May 2013)

• Record Type: Journal Article
• Authors: Romanos, Jihane; Rosén, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; van Heel, David A; Cukrowska, Bozena; Bruno, Valentina; Mazzilli, Maria Cristina; Núñez, Concepcion; Bilbao, Jose Ramon; Mearin, M Luisa; Barisani, Donatella; Rewers, Marian; Norris, Jill M; Ivarsson, Anneli; Boezen, H Marieke; Liu, Edwin; Wijmenga, Cisca
• Other Names: Scerri Cristian author non-byline.; Koltai Tunde author non-byline.; Kolaček Sanja author non-byline.; Mišak Zrinka author non-byline.; Abdović Slaven author non-byline.; Koletzko Sibylle author non-byline.; Osiander Gertraud author non-byline.; Werkstetter Katharina author non-byline.; Mummert Eckart author non-byline.; Korponay-Szabo Ilma R author non-byline.; Gyimesi Judit author non-byline.; Shamir Raanan author non-byline.; Hartman Corina author non-byline.; Bravi Enzo author non-byline.; Poles Marco author non-byline.; Auricchio Renata author non-byline.; Limongelli G Gianna Giovamma author non-byline.; Greco Luigi author non-byline.; Troncone Riccardo author non-byline.; Villanacci Vincenzo author non-byline.; Bindels Jacques G author non-byline.; Brand Ronald author non-byline.; Kupper Bibi Funke author non-byline.; Esch Caroline E Hogen author non-byline.; Hopman Erica G author non-byline.; Koning Frits author non-byline.; Kooy-Winkelaar Yvonne author non-byline.; te Marvelde Chantal author non-byline.; Putter Hein author non-byline.; Stoopman Els author non-byline.; Vriezinga Sabine author non-byline.; Sollid Ludvig M author non-byline.; Ráki Melinda author non-byline.; Chmielewska Ania author non-byline.; Dziechciarz Piotr author non-byline.; Pieścik-Lech Małgorzata author non-byline.; Szajewska Hania author non-byline.; Szaflarska-Szczepanik Anna author non-byline.; Castillejo Gemma author non-byline.; Capilla Amalia author non-byline.; Varea Vicente author non-byline.; Ribes-Koninckx Carmen author non-byline.; Lopez Anna author non-byline.; Crespo Paula author non-byline.; Martinez Eva author non-byline.; Polanco Isabel author non-byline.; Högberg Lotta author non-byline.; Stenhammar Lars author non-byline.; Carlsson Annelie author non-byline.; Webb Charlotta author non-byline.; Hammarroth Solveig author non-byline.; Hernell Olle author non-byline.; Lagerqvist Carina author non-byline.; Myléus Anna author non-byline.; Nordyke Katrina author non-byline.; Norström Fredrik author non-byline.; Sandström Olof author non-byline.; Wall Stig author non-byline.; Karlsson Eva author non-byline.;
• Is Part Of: Gut. Volume 63:Issue 3(2014)
• Page Start: 415
• Page End: 422
• Publication Date: 2013-05-23
• Subjects: Coeliac Disease -- Genetic Testing -- Hla -- Molecular Genetics -- Celiac Disease; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2012-304110
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case–control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD.