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.
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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