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

Immunology and Immunotherapy

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

460 Citations (Scopus)

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 x 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 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 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.

Original language	English
Pages (from-to)	698-702
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	8
DOIs	https://doi.org/10.1038/ng.625
Publication status	Published - 2010

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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{37af076017bb46aba3a5bba5f284caa7,

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 x 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 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 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.",

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 Young-Hun Cho 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",

doi = "10.1038/ng.625",

language = "English",

volume = "42",

pages = "698--702",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Publishing Group",

number = "8",

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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, Y-H, 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

Y1 - 2010

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 x 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 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 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.

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 x 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 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 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.

U2 - 10.1038/ng.625

DO - 10.1038/ng.625

M3 - Article

C2 - 20622878

SN - 1546-1718

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

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