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

doi:10.1038/ng.2551

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

Arcispedale Santa Maria Nuova

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	319-324
Number of pages	6
Journal	Nature Genetics
Volume	45
Issue number	3
DOIs	https://doi.org/10.1038/ng.2551
Publication status	Published - Mar 2013

ASJC Scopus subject areas

Genetics

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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, 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 journal › Article › peer-review

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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abstract = "Beh{\c c}et'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 Beh{\c c}et'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 Beh{\c c}et'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 Beh{\c c}et'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.",

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AU - Aksu, Kenan

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

AU - Saruhan-Direskeneli, Güher

AU - Sawalha, Amr H.

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

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