Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease

Travis Hughes, Patrick Coit, Adam Adler, Vuslat Yilmaz, Kenan Aksu, Nursen Düzgün, Gokhan Keser, Ayse Cefle, Ayten Yazici, Andac Ergen, Erkan Alpsoy, Carlo Salvarani, Bruno Casali, Ina Kötter, Javier Gutierrez-Achury, Cisca Wijmenga, Haner Direskeneli, Güher Saruhan-Direskeneli, Amr H. Sawalha

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Abstract

Behçet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behçet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behçet's disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behçet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 × 10 -50). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 × 10 -26), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 × 10 -14) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 × 10 -18) were also identified and replicated.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalNature Genetics
Volume45
Issue number3
DOIs
Publication statusPublished - Mar 2013

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HLA Antigens
Odds Ratio
Oral Ulcer
Linkage Disequilibrium
Single Nucleotide Polymorphism
Meta-Analysis
Alleles

ASJC Scopus subject areas

  • Genetics

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Hughes, T., Coit, P., Adler, A., Yilmaz, V., Aksu, K., Düzgün, N., ... Sawalha, A. H. (2013). Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease. Nature Genetics, 45(3), 319-324. https://doi.org/10.1038/ng.2551

Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease. / Hughes, Travis; Coit, Patrick; Adler, Adam; Yilmaz, Vuslat; Aksu, Kenan; Düzgün, Nursen; Keser, Gokhan; Cefle, Ayse; Yazici, Ayten; Ergen, Andac; Alpsoy, Erkan; Salvarani, Carlo; Casali, Bruno; Kötter, Ina; Gutierrez-Achury, Javier; Wijmenga, Cisca; Direskeneli, Haner; Saruhan-Direskeneli, Güher; Sawalha, Amr H.

In: Nature Genetics, Vol. 45, No. 3, 03.2013, p. 319-324.

Research output: Contribution to journalArticle

Hughes, T, Coit, P, Adler, A, Yilmaz, V, Aksu, K, Düzgün, N, Keser, G, Cefle, A, Yazici, A, Ergen, A, Alpsoy, E, Salvarani, C, Casali, B, Kötter, I, Gutierrez-Achury, J, Wijmenga, C, Direskeneli, H, Saruhan-Direskeneli, G & Sawalha, AH 2013, 'Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease', Nature Genetics, vol. 45, no. 3, pp. 319-324. https://doi.org/10.1038/ng.2551
Hughes, Travis ; Coit, Patrick ; Adler, Adam ; Yilmaz, Vuslat ; Aksu, Kenan ; Düzgün, Nursen ; Keser, Gokhan ; Cefle, Ayse ; Yazici, Ayten ; Ergen, Andac ; Alpsoy, Erkan ; Salvarani, Carlo ; Casali, Bruno ; Kötter, Ina ; Gutierrez-Achury, Javier ; Wijmenga, Cisca ; Direskeneli, Haner ; Saruhan-Direskeneli, Güher ; Sawalha, Amr H. / Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease. In: Nature Genetics. 2013 ; Vol. 45, No. 3. pp. 319-324.
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AU - Düzgün, Nursen

AU - Keser, Gokhan

AU - Cefle, Ayse

AU - Yazici, Ayten

AU - Ergen, Andac

AU - Alpsoy, Erkan

AU - Salvarani, Carlo

AU - Casali, Bruno

AU - Kötter, Ina

AU - Gutierrez-Achury, Javier

AU - Wijmenga, Cisca

AU - Direskeneli, Haner

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AU - Sawalha, Amr H.

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