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 | |
| Publication status | Published - Mar 2013 |
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ASJC Scopus subject areas
- Genetics
Cite this
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
}
TY - JOUR
T1 - Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease
AU - Hughes, Travis
AU - Coit, Patrick
AU - Adler, Adam
AU - Yilmaz, Vuslat
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.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84874645442&partnerID=8YFLogxK
U2 - 10.1038/ng.2551
DO - 10.1038/ng.2551
M3 - Article
VL - 45
SP - 319
EP - 324
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 3
ER -