Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

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Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

Romanos, Jihane (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands; School of Medicine, Lebanese American University, Beirut, Lebanon,Immunogenetics Research Laboratory, Hospital de Cruces, Bizkaia, Spain

Rosén, Anna (författare): Umeå University,Umeå universitet,Epidemiologi och global hälsa,Institutionen för medicinsk biovetenskap,Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden; Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden

Kumar, Vinod (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands

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Trynka, Gosia (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands; Division of Genetics and Division of Rheumatology, Harvard Medical School, Brigham and Womens Hospital, Boston, MA, United States

Franke, Lude (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands

Szperl, Agata (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands

Gutierrez-Achury, Javier (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands

van Diemen, Cleo C (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands

Kanninga, Roan (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, Netherlands

Jankipersadsing, Soesma A (författare): University Medical Center Groningen

Steck, Andrea (författare): Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States

Eisenbarth, Georges (författare): Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States

van Heel, David A (författare): Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom,Queen Mary University

Cukrowska, Bozena (författare): Department of Pathology, Childrens Memorial Health Institute, Warsaw, Poland

Bruno, Valentina (författare): European Laboratory for Food-Induced Disease, University of of Naples Federico II, Naples, Italy

Mazzilli, Maria Cristina (författare): Department of Molecular Medicine, Sapienza University of of Rome, Rome, Italy

Núñez, Concepcion (författare): Clinical Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos IdISSC, Madrid, Spain

Bilbao, Jose Ramon (författare): Hospital de Cruces

Mearin, M Luisa (författare): Department of Paediatrics, Leiden University of Medical Centre, Leiden, Netherlands

Barisani, Donatella (författare): Department of Experimental Medicine, Faculty of Medicine, University of of Milano- Bicocca, Monza, Italy,European Institute of Oncology

Rewers, Marian (författare): Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States

Norris, Jill M (författare): Epidemiology Department, Colorado School of Public Health, Aurora, United States

Ivarsson, Anneli (författare): Lund University,Lunds universitet,Umeå University,Umeå universitet,Epidemiologi och global hälsa,Department of Public Health and Clinical Medicine, Epidemiology and Global Health, Umeå University, Umeå, Sweden,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Pediatrisk autoimmunitet,Forskargrupper vid Lunds universitet,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Pediatric Autoimmunity,Lund University Research Groups

Boezen, H Marieke (författare): Department of Epidemiology, University of of Groningen, University of Medical Centre Groningen, Groningen, Netherlands

Liu, Edwin (författare): Barbara Davis Centre for Childhood Diabetes, University of of Colorado Denver, Aurora, CO, United States

Wijmenga, Cisca (författare): Department of Genetics, University of of Groningen, University of Medical Centre Groningen, PO Box 30001, Groningen 9700 RB, Netherlands

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2013-05-23
2014
Engelska.
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 63:3, s. 415-422

Relaterad länk:: https://gut.bmj.com/...; visa fler...; http://dx.doi.org/10... (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; https://lup.lub.lu.s...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Celiac Disease
Coeliac Disease
Genetic Testing
Hla
Molecular Genetics

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Artiklar i publikationen: Gut

Av lärosätet: Umeå universitet; Linköpings universitet; Lunds universitet

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