Identification of multiple genetic susceptibility loci in Takayasu arteritis

Güher Saruhan-Direskeneli; Travis Hughes; Kenan Aksu; Gokhan Keser; Patrick Coit; Sibel Z. Aydin; Fatma Alibaz-Oner; Sevil Kamali; Murat Inanc; Simon Carette; Gary S. Hoffman; Servet Akar; Fatos Onen; Nurullah Akkoc; Nader A. Khalidi; Curry Koening; Omer Karadag; Sedat Kiraz; Carol A. Langford; Carol A. McAlear; Zeynep Ozbalkan; Askin Ates; Yasar Karaaslan; Kathleen Maksimowicz-Mckinnon; Paul A. Monach; Hüseyin T. Ozer; Emire Seyahi; Izzet Fresko; Ayse Cefle; Philip Seo; Kenneth J. Warrington; Mehmet A. Ozturk; Steven R. Ytterberg; Veli Cobankara; A. Mesut Onat; Joel M. Guthridge; Judith A. James; Ercan Tunc; Nurşen Duzgun; Muge Bicakcigil; Sibel P. Yentür; Peter A. Merkel; Haner Direskeneli; Amr H. Sawalha

doi:10.1016/j.ajhg.2013.05.026

Identification of multiple genetic susceptibility loci in Takayasu arteritis

Güher Saruhan-Direskeneli, Travis Hughes, Kenan Aksu, Gokhan Keser, Patrick Coit, Sibel Z. Aydin, Fatma Alibaz-Oner, Sevil Kamali, Murat Inanc, Simon Carette, Gary S. Hoffman, Servet Akar, Fatos Onen, Nurullah Akkoc, Nader A. Khalidi, Curry Koening, Omer Karadag, Sedat Kiraz, Carol A. Langford, Carol A. McAlearZeynep Ozbalkan, Askin Ates, Yasar Karaaslan, Kathleen Maksimowicz-Mckinnon, Paul A. Monach, Hüseyin T. Ozer, Emire Seyahi, Izzet Fresko, Ayse Cefle, Philip Seo, Kenneth J. Warrington, Mehmet A. Ozturk, Steven R. Ytterberg, Veli Cobankara, A. Mesut Onat, Joel M. Guthridge, Judith A. James, Ercan Tunc, Nurşen Duzgun, Muge Bicakcigil, Sibel P. Yentür, Peter A. Merkel, Haner Direskeneli, Amr H. Sawalha

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

105 Scopus citations

Abstract

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ∼200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r ² < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10^-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10^-9; and rs189754752, OR = 2.47, p = 4.22 × 10 ^-9). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10^-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10^-8).

Original language	English (US)
Pages (from-to)	298-305
Number of pages	8
Journal	American journal of human genetics
Volume	93
Issue number	2
DOIs	https://doi.org/10.1016/j.ajhg.2013.05.026
State	Published - Aug 8 2013
Externally published	Yes

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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Saruhan-Direskeneli, G., Hughes, T., Aksu, K., Keser, G., Coit, P., Aydin, S. Z., Alibaz-Oner, F., Kamali, S., Inanc, M., Carette, S., Hoffman, G. S., Akar, S., Onen, F., Akkoc, N., Khalidi, N. A., Koening, C., Karadag, O., Kiraz, S., Langford, C. A., ... Sawalha, A. H. (2013). Identification of multiple genetic susceptibility loci in Takayasu arteritis. American journal of human genetics, 93(2), 298-305. https://doi.org/10.1016/j.ajhg.2013.05.026

Saruhan-Direskeneli, G, Hughes, T, Aksu, K, Keser, G, Coit, P, Aydin, SZ, Alibaz-Oner, F, Kamali, S, Inanc, M, Carette, S, Hoffman, GS, Akar, S, Onen, F, Akkoc, N, Khalidi, NA, Koening, C, Karadag, O, Kiraz, S, Langford, CA, McAlear, CA, Ozbalkan, Z, Ates, A, Karaaslan, Y, Maksimowicz-Mckinnon, K, Monach, PA, Ozer, HT, Seyahi, E, Fresko, I, Cefle, A, Seo, P, Warrington, KJ, Ozturk, MA, Ytterberg, SR, Cobankara, V, Onat, AM, Guthridge, JM, James, JA, Tunc, E, Duzgun, N, Bicakcigil, M, Yentür, SP, Merkel, PA, Direskeneli, H & Sawalha, AH 2013, 'Identification of multiple genetic susceptibility loci in Takayasu arteritis', American journal of human genetics, vol. 93, no. 2, pp. 298-305. https://doi.org/10.1016/j.ajhg.2013.05.026

@article{4518caea72b44ffaae0a9babd2d0a719,

title = "Identification of multiple genetic susceptibility loci in Takayasu arteritis",

abstract = "Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ∼200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r 2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10 -9). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10-8).",

author = "G{\"u}her Saruhan-Direskeneli and Travis Hughes and Kenan Aksu and Gokhan Keser and Patrick Coit and Aydin, {Sibel Z.} and Fatma Alibaz-Oner and Sevil Kamali and Murat Inanc and Simon Carette and Hoffman, {Gary S.} and Servet Akar and Fatos Onen and Nurullah Akkoc and Khalidi, {Nader A.} and Curry Koening and Omer Karadag and Sedat Kiraz and Langford, {Carol A.} and McAlear, {Carol A.} and Zeynep Ozbalkan and Askin Ates and Yasar Karaaslan and Kathleen Maksimowicz-Mckinnon and Monach, {Paul A.} and Ozer, {H{\"u}seyin T.} and Emire Seyahi and Izzet Fresko and Ayse Cefle and Philip Seo and Warrington, {Kenneth J.} and Ozturk, {Mehmet A.} and Ytterberg, {Steven R.} and Veli Cobankara and Onat, {A. Mesut} and Guthridge, {Joel M.} and James, {Judith A.} and Ercan Tunc and Nur{\c s}en Duzgun and Muge Bicakcigil and Yent{\"u}r, {Sibel P.} and Merkel, {Peter A.} and Haner Direskeneli and Sawalha, {Amr H.}",

note = "Funding Information: This work was supported by funding from the University of Michigan and the Vasculitis Foundation. Procurement and genotyping of the European-American control samples was supported by the National Institutes of Health grants GM103510, AR053483, AI08714, and AI101914. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. ",

year = "2013",

month = aug,

day = "8",

doi = "10.1016/j.ajhg.2013.05.026",

language = "English (US)",

volume = "93",

pages = "298--305",

journal = "American journal of human genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Identification of multiple genetic susceptibility loci in Takayasu arteritis

AU - Saruhan-Direskeneli, Güher

AU - Hughes, Travis

AU - Aksu, Kenan

AU - Keser, Gokhan

AU - Coit, Patrick

AU - Aydin, Sibel Z.

AU - Alibaz-Oner, Fatma

AU - Kamali, Sevil

AU - Inanc, Murat

AU - Carette, Simon

AU - Hoffman, Gary S.

AU - Akar, Servet

AU - Onen, Fatos

AU - Akkoc, Nurullah

AU - Khalidi, Nader A.

AU - Koening, Curry

AU - Karadag, Omer

AU - Kiraz, Sedat

AU - Langford, Carol A.

AU - McAlear, Carol A.

AU - Ozbalkan, Zeynep

AU - Ates, Askin

AU - Karaaslan, Yasar

AU - Maksimowicz-Mckinnon, Kathleen

AU - Monach, Paul A.

AU - Ozer, Hüseyin T.

AU - Seyahi, Emire

AU - Fresko, Izzet

AU - Cefle, Ayse

AU - Seo, Philip

AU - Warrington, Kenneth J.

AU - Ozturk, Mehmet A.

AU - Ytterberg, Steven R.

AU - Cobankara, Veli

AU - Onat, A. Mesut

AU - Guthridge, Joel M.

AU - James, Judith A.

AU - Tunc, Ercan

AU - Duzgun, Nurşen

AU - Bicakcigil, Muge

AU - Yentür, Sibel P.

AU - Merkel, Peter A.

AU - Direskeneli, Haner

AU - Sawalha, Amr H.

N1 - Funding Information: This work was supported by funding from the University of Michigan and the Vasculitis Foundation. Procurement and genotyping of the European-American control samples was supported by the National Institutes of Health grants GM103510, AR053483, AI08714, and AI101914. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences.

PY - 2013/8/8

Y1 - 2013/8/8

N2 - Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ∼200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r 2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10 -9). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10-8).

AB - Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ∼200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r 2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10 -9). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10-8).

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DO - 10.1016/j.ajhg.2013.05.026

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SN - 0002-9297

VL - 93

SP - 298

EP - 305

JO - American journal of human genetics

JF - American journal of human genetics

IS - 2

ER -

Identification of multiple genetic susceptibility loci in Takayasu arteritis

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