Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease

Elaine F. Remmers; Fulya Cosan; Yohei Kirino; Michael J. Ombrello; Neslihan Abaci; Colleen Satorius; Julie M. Le; Barbara Yang; Benjamin D. Korman; Aris Cakiris; Oznur Aglar; Zeliha Emrence; Hulya Azakli; Duran Ustek; Ilknur Tugal-Tutkun; Gulsen Akman-Demir; Wei Chen; Christopher I. Amos; Michael B. Dizon; Afet Akdag Kose; Gulsevim Azizlerli; Burak Erer; Oliver J. Brand; Virginia G. Kaklamani; Phaedon Kaklamanis; Eldad Ben-Chetrit; Miles Stanford; Farida Fortune; Marwen Ghabra; William E R Ollier; Young Hun Cho; Dongsik Bang; John O'Shea; Graham R. Wallace; Massimo Gadina; Daniel L. Kastner; Ahmet Gül

doi:10.1038/ng.625

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease

Elaine F. Remmers, Fulya Cosan, Yohei Kirino, Michael J. Ombrello, Neslihan Abaci, Colleen Satorius, Julie M. Le, Barbara Yang, Benjamin D. Korman, Aris Cakiris, Oznur Aglar, Zeliha Emrence, Hulya Azakli, Duran Ustek, Ilknur Tugal-Tutkun, Gulsen Akman-Demir, Wei Chen, Christopher I. Amos, Michael B. Dizon, Afet Akdag KoseGulsevim Azizlerli, Burak Erer, Oliver J. Brand, Virginia G. Kaklamani, Phaedon Kaklamanis, Eldad Ben-Chetrit, Miles Stanford, Farida Fortune, Marwen Ghabra, William E R Ollier, Young Hun Cho, Dongsik Bang, John O'Shea, Graham R. Wallace, Massimo Gadina, Daniel L. Kastner, Ahmet Gül

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

Abstract

Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10-8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10-18, odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10 -9, OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production. © 2010 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	698-702
Number of pages	4
Journal	Nature Genetics
Volume	42
Issue number	8
DOIs	https://doi.org/10.1038/ng.625
Publication status	Published - Aug 2010

Access to Document

10.1038/ng.625

Cite this

Remmers, E. F., Cosan, F., Kirino, Y., Ombrello, M. J., Abaci, N., Satorius, C., Le, J. M., Yang, B., Korman, B. D., Cakiris, A., Aglar, O., Emrence, Z., Azakli, H., Ustek, D., Tugal-Tutkun, I., Akman-Demir, G., Chen, W., Amos, C. I., Dizon, M. B., ... Gül, A. (2010). Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease. Nature Genetics, 42(8), 698-702. https://doi.org/10.1038/ng.625

@article{b1ec46695c2c47b9bee968eeba1773f8,

title = "Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Beh{\c c}et's disease",

abstract = "Beh{\c c}et's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Beh{\c c}et's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Beh{\c c}et's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10-8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10-18, odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10 -9, OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production. {\textcopyright} 2010 Nature America, Inc. All rights reserved.",

author = "Remmers, {Elaine F.} and Fulya Cosan and Yohei Kirino and Ombrello, {Michael J.} and Neslihan Abaci and Colleen Satorius and Le, {Julie M.} and Barbara Yang and Korman, {Benjamin D.} and Aris Cakiris and Oznur Aglar and Zeliha Emrence and Hulya Azakli and Duran Ustek and Ilknur Tugal-Tutkun and Gulsen Akman-Demir and Wei Chen and Amos, {Christopher I.} and Dizon, {Michael B.} and Kose, {Afet Akdag} and Gulsevim Azizlerli and Burak Erer and Brand, {Oliver J.} and Kaklamani, {Virginia G.} and Phaedon Kaklamanis and Eldad Ben-Chetrit and Miles Stanford and Farida Fortune and Marwen Ghabra and Ollier, {William E R} and Cho, {Young Hun} and Dongsik Bang and John O'Shea and Wallace, {Graham R.} and Massimo Gadina and Kastner, {Daniel L.} and Ahmet G{\"u}l",

year = "2010",

month = aug,

doi = "10.1038/ng.625",

language = "English",

volume = "42",

pages = "698--702",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

Remmers, EF, Cosan, F, Kirino, Y, Ombrello, MJ, Abaci, N, Satorius, C, Le, JM, Yang, B, Korman, BD, Cakiris, A, Aglar, O, Emrence, Z, Azakli, H, Ustek, D, Tugal-Tutkun, I, Akman-Demir, G, Chen, W, Amos, CI, Dizon, MB, Kose, AA, Azizlerli, G, Erer, B, Brand, OJ, Kaklamani, VG, Kaklamanis, P, Ben-Chetrit, E, Stanford, M, Fortune, F, Ghabra, M, Ollier, WER, Cho, YH, Bang, D, O'Shea, J, Wallace, GR, Gadina, M, Kastner, DL & Gül, A 2010, 'Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease', Nature Genetics, vol. 42, no. 8, pp. 698-702. https://doi.org/10.1038/ng.625

TY - JOUR

T1 - Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease

AU - Remmers, Elaine F.

AU - Cosan, Fulya

AU - Kirino, Yohei

AU - Ombrello, Michael J.

AU - Abaci, Neslihan

AU - Satorius, Colleen

AU - Le, Julie M.

AU - Yang, Barbara

AU - Korman, Benjamin D.

AU - Cakiris, Aris

AU - Aglar, Oznur

AU - Emrence, Zeliha

AU - Azakli, Hulya

AU - Ustek, Duran

AU - Tugal-Tutkun, Ilknur

AU - Akman-Demir, Gulsen

AU - Chen, Wei

AU - Amos, Christopher I.

AU - Dizon, Michael B.

AU - Kose, Afet Akdag

AU - Azizlerli, Gulsevim

AU - Erer, Burak

AU - Brand, Oliver J.

AU - Kaklamani, Virginia G.

AU - Kaklamanis, Phaedon

AU - Ben-Chetrit, Eldad

AU - Stanford, Miles

AU - Fortune, Farida

AU - Ghabra, Marwen

AU - Ollier, William E R

AU - Cho, Young Hun

AU - Bang, Dongsik

AU - O'Shea, John

AU - Wallace, Graham R.

AU - Gadina, Massimo

AU - Kastner, Daniel L.

AU - Gül, Ahmet

PY - 2010/8

Y1 - 2010/8

N2 - Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10-8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10-18, odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10 -9, OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production. © 2010 Nature America, Inc. All rights reserved.

AB - Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10-8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10-18, odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10 -9, OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production. © 2010 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.625

DO - 10.1038/ng.625

M3 - Article

C2 - 20622878

SN - 1061-4036

VL - 42

SP - 698

EP - 702

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease

Abstract

Access to Document

Fingerprint

Cite this