RT Journal Article
SR Electronic
T1 Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 415
OP 422
DO 10.1136/gutjnl-2012-304110
VO 63
IS 3
A1 Jihane Romanos
A1 Anna Rosén
A1 Vinod Kumar
A1 Gosia Trynka
A1 Lude Franke
A1 Agata Szperl
A1 Javier Gutierrez-Achury
A1 Cleo C van Diemen
A1 Roan Kanninga
A1 Soesma A Jankipersadsing
A1 Andrea Steck
A1 Georges Eisenbarth
A1 David A van Heel
A1 Bozena Cukrowska
A1 Valentina Bruno
A1 Maria Cristina Mazzilli
A1 Concepcion Núñez
A1 Jose Ramon Bilbao
A1 M Luisa Mearin
A1 Donatella Barisani
A1 Marian Rewers
A1 Jill M Norris
A1 Anneli Ivarsson
A1 H Marieke Boezen
A1 Edwin Liu
A1 Cisca Wijmenga
A1 PreventCD Group
YR 2014
UL http://gut.bmj.com/content/63/3/415.abstract
AB 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.