Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants
Autor: | Romanos, J., Rosén, A., Kumar, V., Trynka, G., Franke, L., Szperl, A., Gutierrez-Achury, J., van Diemen, C.C., Kanninga, R., Jankipersadsing, S.A., Steck, A., Eisenbarth, G., van Heel, D.A., Cukrowska, B., Bruno, V., Mazzilli, M.C., Núñez, C., Bilbao, J.R., Mearin, M.L., Barisani, D., Rewers, M., Norris, J.M., Ivarsson, A., Boezen. H.M., Liu, E., Wijmenga, C., Prevent, C.D., Kolaček, Sanja, Steck, A, Mearin, M, L, Barisani, D, Rewers, M, Boezen, H.M. |
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Přispěvatelé: | Romanos, J, Rosen, A, Kumar, V, Trynka, G, Franke, L, Szperl, A, Gutierrez Achury, J, Van Diemen, Cc, Kanninga, R, Jankipersadsing, Sa, Steck, A, Eisenbarth, G, van Heel, Da, Cukrowska, B, Bruno, V, Mazzilli, Mc, Nunez, C, Bilbao, Jr, Mearin, Ml, Barisani, D, Rewers, M, Norris, Jm, Ivarsson, A, Boezen, Hm, Liu, E, Wijmenga, C, Auricchio, Renata, Prevent CD, G. r. o. u. p., Rosén, A, van Diemen, C, Jankipersadsing, S, van Heel, D, Mazzilli, M, Núñez, C, Bilbao, J, Mearin, M, Norris, J, Boezen, H, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL) |
Rok vydání: | 2013 |
Předmět: |
Male
INCREASING PREVALENCE ACCURACY AUTOIMMUNITY Genome-wide association study Human chromosome abnormalities -- Diagnosis Celiac disease Elméleti orvostudományok Prospective Studies MULTIPLE COMMON education.field_of_study medicine.diagnostic_test Gastroenterology Orvostudományok 3. Good health Hla Female Risk assessment Genetic Markers Population Single-nucleotide polymorphism Human leukocyte antigen GENETIC RISK Coeliac Disease Polymorphism Single Nucleotide Risk Assessment Decision Support Techniques Molecular Genetics Molecular Genetic HLA-DQ Antigens medicine Genetics LINKAGE SNP Humans Genetic Predisposition to Disease Genetic Testing GENOME-WIDE ASSOCIATION education Genetic testing Proportional Hazards Models Models Genetic business.industry Case-control study BIO/13 - BIOLOGIA APPLICATA ALLELES Celiac Disease Logistic Models ROC Curve Case-Control Studies Immunology business |
Zdroj: | Gut Gut, 63(3), 415-422 Europe PubMed Central Gut, 63(3), 415-422. BMJ PUBLISHING GROUP |
ISSN: | 1468-3288 0017-5749 |
Popis: | 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. peer-reviewed |
Databáze: | OpenAIRE |
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