This article is part of the supplement: Genetic Analysis Workshop 15: Gene Expression Analysis and Approaches to Detecting Multiple Functional Loci

Open Access Proceedings

Modeling of PTPN22 and HLA-DRB1 susceptibility to rheumatoid arthritis

France Gagnon1*, David Hajage2, Sabine Plancoulaine3 and Sophie Tezenas du Montcel2*

Author Affiliations

1 Department of Public Health Sciences, Faculty of Medicine, University of Toronto, 155 College Street, Toronto, Ontario, M5T 3M7, Canada

2 Université Pierre et Marie Curie-Paris 6, EA3974 Modélisation en Recherche Clinique, Paris, F-75013, France, AP-HP, Groupe Hospitalier Pitié-Salpétrière, Département de Santé Publique, Unité de Biostatistique et Information Médicale, Paris, F-75013, France

3 INSERM, U550, Paris, F-75015, France; Laboratoire de Génétique Humaine des Maladies Infectieuses, Faculté de Médecine René Descartes, Université de Paris René Descartes, site Necker, Paris, F-75015, France

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BMC Proceedings 2007, 1(Suppl 1):S14  doi:

Published: 18 December 2007


In the present paper, we used the North American Rheumatoid Arthritis Consortium data provided for Genetic Analysis Workshop 15 Problem 2 to: 1) estimate the penetrances of PTPN22 and HLA-DRB1 and, 2) test the selected model of PTPN22 conditional on the rheumatoid factor status. To achieve these aims, we used the marker association segregation chi-square method, fitting simultaneously both genotype frequency and identical by descent distributions in a sample of 3690 White individuals from 604 nuclear families. A co-dominant model fitted the rs2476601 (R620W) single-nucleotide polymorphism (SNP) of the PTPN22 gene well, whereas a lack of fit for all models was observed for the HLA-DRB1 locus. Testing genetic models of rheumatoid arthritis that include the PTPN22 SNP in addition to the HLA-DRB1 locus did not affect the results, nor did subgroup analysis of PTPN22 conditional on the rheumatoid factor status. In conclusion, PTPN22 R620W SNP is a risk factor for rheumatoid arthritis. The genetic architecture of the HLA-DRB1 locus is highly complex, and more elaborate modeling of this locus is required.