Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

F. David Carmona; Patrick Coit; Güher Saruhan-Direskeneli; José Hernández-Rodríguez; María C. Cid; Roser Solans; Santos Castañeda; Augusto Vaglio; Haner Direskeneli; Peter A. Merkel; Luigi Boiardi; Carlo Salvarani; Miguel A. González-Gay; Javier Martín; Amr H. Sawalha; A. Martínez-Berriochoa; A. Unzurrunzaga; A. Hidalgo-Conde; A. B. Vuelta; A. Fernández-Nebro; M. C. Ordóñez-Cañizares; B. Fernández-Gutiérrez; L. Rodríguez-Rodríguez; B. Escalante; B. Marí-Alfonso; B. Sopeña; C. Gómez-Vaquero; E. Raya; E. Grau; J. A. Román; E. F. Vicente; E. de Miguel; F. J. López-Longo; L. Martínez; I. C. Morado; J. B. Díaz-López; L. Caminal-Montero; A. Martínez-Zapico; J. Narváez; J. Monfort; L. Tío; J. A. Miranda-Filloy; J. Sánchez-Martín; J. J. Alegre-Sancho; L. Sáez-Comet; M. Pérez-Conesa; M. Corbera-Bellalta; M. Ramentol-Sintas; M. J. García-Villanueva; M. Guijarro Rojas; N. Ortego-Centeno; R. Ríos Fernández; J. L. Callejas; O. Sanchez Pernaute; P. Fanlo Mateo; R. Blanco; S. Prieto-González; V. M. Martínez-Taboada; A. Soriano; C. Lunardi; D. Gianfreda; D. Santilli; F. Bonatti; F. Muratore; G. Pazzola; O. Addimanda; G. Emmi; G. A. Ramirez; L. Beretta; M. Govoni; M. A. Cimmino; A. Mesut Onat; A. Cefle; A. Yazici; B. Kısacık; E. Dalkilic; E. Seyahi; I. Fresko; E. Tunc; E. Erken; H. Te Ozer; K. Aksu; G. Keser; M. A. Ozturk; M. Bıcakcıgil; N. Duzgun; O. Karadag; S. Kiraz; O. N. Pamuk; S. Akar; F. Onen; N. Akkoc; S. Kamali; M. Inanc; S. P. Yentür; S. Z. Aydin; F. Alibaz-Oner; T. Kaşifoğlu; V. Cobankara; Z. Ozbalkan

doi:https://doi.org/10.1038/srep43953

Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

F. David Carmona, Patrick Coit, Güher Saruhan-Direskeneli, José Hernández-Rodríguez, María C. Cid, Roser Solans, Santos Castañeda, Augusto Vaglio, Haner Direskeneli, Peter A. Merkel, Luigi Boiardi, Carlo Salvarani, Miguel A. González-Gay, Javier Martín, Amr H. Sawalha, A. Martínez-Berriochoa, A. Unzurrunzaga, A. Hidalgo-Conde, A. B. Vuelta, A. Fernández-NebroM. C. Ordóñez-Cañizares, B. Fernández-Gutiérrez, L. Rodríguez-Rodríguez, B. Escalante, B. Marí-Alfonso, B. Sopeña, C. Gómez-Vaquero, E. Raya, E. Grau, J. A. Román, E. F. Vicente, E. de Miguel, F. J. López-Longo, L. Martínez, I. C. Morado, J. B. Díaz-López, L. Caminal-Montero, A. Martínez-Zapico, J. Narváez, J. Monfort, L. Tío, J. A. Miranda-Filloy, J. Sánchez-Martín, J. J. Alegre-Sancho, L. Sáez-Comet, M. Pérez-Conesa, M. Corbera-Bellalta, M. Ramentol-Sintas, M. J. García-Villanueva, M. Guijarro Rojas, N. Ortego-Centeno, R. Ríos Fernández, J. L. Callejas, O. Sanchez Pernaute, P. Fanlo Mateo, R. Blanco, S. Prieto-González, V. M. Martínez-Taboada, A. Soriano, C. Lunardi, D. Gianfreda, D. Santilli, F. Bonatti, F. Muratore, G. Pazzola, O. Addimanda, G. Emmi, G. A. Ramirez, L. Beretta, M. Govoni, M. A. Cimmino, A. Mesut Onat, A. Cefle, A. Yazici, B. Kısacık, E. Dalkilic, E. Seyahi, I. Fresko, E. Tunc, E. Erken, H. Te Ozer, K. Aksu, G. Keser, M. A. Ozturk, M. Bıcakcıgil, N. Duzgun, O. Karadag, S. Kiraz, O. N. Pamuk, S. Akar, F. Onen, N. Akkoc, S. Kamali, M. Inanc, S. P. Yentür, S. Z. Aydin, F. Alibaz-Oner, T. Kaşifoğlu, V. Cobankara, Z. Ozbalkan

Department of Medicine

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Abstract

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; OR GCA = 1.19, OR TAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P GCA = 5.52E-04, OR GCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

Original language	English
Article number	43953
Journal	SCIENTIFIC REPORTS
Volume	7
DOIs	https://doi.org/10.1038/srep43953
Publication status	Published - 9 Mar 2017

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Carmona, F. D., Coit, P., Saruhan-Direskeneli, G., Hernández-Rodríguez, J., Cid, M. C., Solans, R., Castañeda, S., Vaglio, A., Direskeneli, H., Merkel, P. A., Boiardi, L., Salvarani, C., González-Gay, M. A., Martín, J., Sawalha, A. H., Martínez-Berriochoa, A., Unzurrunzaga, A., Hidalgo-Conde, A., Vuelta, A. B., ... Ozbalkan, Z. (2017). Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. SCIENTIFIC REPORTS, 7, [43953]. https://doi.org/10.1038/srep43953

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title = "Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy",

abstract = "Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; OR GCA = 1.19, OR TAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P GCA = 5.52E-04, OR GCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.",

author = "Carmona, {F. David} and Patrick Coit and G{\"u}her Saruhan-Direskeneli and Jos{\'e} Hern{\'a}ndez-Rodr{\'i}guez and Cid, {Mar{\'i}a C.} and Roser Solans and Santos Casta{\~n}eda and Augusto Vaglio and Haner Direskeneli and Merkel, {Peter A.} and Luigi Boiardi and Carlo Salvarani and Gonz{\'a}lez-Gay, {Miguel A.} and Javier Mart{\'i}n and Sawalha, {Amr H.} and A. Mart{\'i}nez-Berriochoa and A. Unzurrunzaga and A. Hidalgo-Conde and Vuelta, {A. B.} and A. Fern{\'a}ndez-Nebro and Ord{\'o}{\~n}ez-Ca{\~n}izares, {M. C.} and B. Fern{\'a}ndez-Guti{\'e}rrez and L. Rodr{\'i}guez-Rodr{\'i}guez and B. Escalante and B. Mar{\'i}-Alfonso and B. Sope{\~n}a and C. G{\'o}mez-Vaquero and E. Raya and E. Grau and Rom{\'a}n, {J. A.} and Vicente, {E. F.} and {de Miguel}, E. and L{\'o}pez-Longo, {F. J.} and L. Mart{\'i}nez and Morado, {I. C.} and D{\'i}az-L{\'o}pez, {J. B.} and L. Caminal-Montero and A. Mart{\'i}nez-Zapico and J. Narv{\'a}ez and J. Monfort and L. T{\'i}o and Miranda-Filloy, {J. A.} and J. S{\'a}nchez-Mart{\'i}n and Alegre-Sancho, {J. J.} and L. S{\'a}ez-Comet and M. P{\'e}rez-Conesa and M. Corbera-Bellalta and M. Ramentol-Sintas and Garc{\'i}a-Villanueva, {M. J.} and {Guijarro Rojas}, M. and N. Ortego-Centeno and {R{\'i}os Fern{\'a}ndez}, R. and Callejas, {J. L.} and {Sanchez Pernaute}, O. and {Fanlo Mateo}, P. and R. Blanco and S. Prieto-Gonz{\'a}lez and Mart{\'i}nez-Taboada, {V. M.} and A. Soriano and C. Lunardi and D. Gianfreda and D. Santilli and F. Bonatti and F. Muratore and G. Pazzola and O. Addimanda and G. Emmi and Ramirez, {G. A.} and L. Beretta and M. Govoni and Cimmino, {M. A.} and {Mesut Onat}, A. and A. Cefle and A. Yazici and B. Kısacık and E. Dalkilic and E. Seyahi and I. Fresko and E. Tunc and E. Erken and {Te Ozer}, H. and K. Aksu and G. Keser and Ozturk, {M. A.} and M. Bıcakcıgil and N. Duzgun and O. Karadag and S. Kiraz and Pamuk, {O. N.} and S. Akar and F. Onen and N. Akkoc and S. Kamali and M. Inanc and Yent{\"u}r, {S. P.} and Aydin, {S. Z.} and F. Alibaz-Oner and T. Ka{\c s}ifoğlu and V. Cobankara and Z. Ozbalkan",

year = "2017",

month = mar,

day = "9",

doi = "https://doi.org/10.1038/srep43953",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

}

Carmona, FD, Coit, P, Saruhan-Direskeneli, G, Hernández-Rodríguez, J, Cid, MC, Solans, R, Castañeda, S, Vaglio, A, Direskeneli, H, Merkel, PA, Boiardi, L, Salvarani, C, González-Gay, MA, Martín, J, Sawalha, AH, Martínez-Berriochoa, A, Unzurrunzaga, A, Hidalgo-Conde, A, Vuelta, AB, Fernández-Nebro, A, Ordóñez-Cañizares, MC, Fernández-Gutiérrez, B, Rodríguez-Rodríguez, L, Escalante, B, Marí-Alfonso, B, Sopeña, B, Gómez-Vaquero, C, Raya, E, Grau, E, Román, JA, Vicente, EF, de Miguel, E, López-Longo, FJ, Martínez, L, Morado, IC, Díaz-López, JB, Caminal-Montero, L, Martínez-Zapico, A, Narváez, J, Monfort, J, Tío, L, Miranda-Filloy, JA, Sánchez-Martín, J, Alegre-Sancho, JJ, Sáez-Comet, L, Pérez-Conesa, M, Corbera-Bellalta, M, Ramentol-Sintas, M, García-Villanueva, MJ, Guijarro Rojas, M, Ortego-Centeno, N, Ríos Fernández, R, Callejas, JL, Sanchez Pernaute, O, Fanlo Mateo, P, Blanco, R, Prieto-González, S, Martínez-Taboada, VM, Soriano, A, Lunardi, C, Gianfreda, D, Santilli, D, Bonatti, F, Muratore, F, Pazzola, G, Addimanda, O, Emmi, G, Ramirez, GA, Beretta, L, Govoni, M, Cimmino, MA, Mesut Onat, A, Cefle, A, Yazici, A, Kısacık, B, Dalkilic, E, Seyahi, E, Fresko, I, Tunc, E, Erken, E, Te Ozer, H, Aksu, K, Keser, G, Ozturk, MA, Bıcakcıgil, M, Duzgun, N, Karadag, O, Kiraz, S, Pamuk, ON, Akar, S, Onen, F, Akkoc, N, Kamali, S, Inanc, M, Yentür, SP, Aydin, SZ, Alibaz-Oner, F, Kaşifoğlu, T, Cobankara, V & Ozbalkan, Z 2017, 'Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy', SCIENTIFIC REPORTS, vol. 7, 43953. https://doi.org/10.1038/srep43953

TY - JOUR

T1 - Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

AU - Carmona, F. David

AU - Coit, Patrick

AU - Saruhan-Direskeneli, Güher

AU - Hernández-Rodríguez, José

AU - Cid, María C.

AU - Solans, Roser

AU - Castañeda, Santos

AU - Vaglio, Augusto

AU - Direskeneli, Haner

AU - Merkel, Peter A.

AU - Boiardi, Luigi

AU - Salvarani, Carlo

AU - González-Gay, Miguel A.

AU - Martín, Javier

AU - Sawalha, Amr H.

AU - Martínez-Berriochoa, A.

AU - Unzurrunzaga, A.

AU - Hidalgo-Conde, A.

AU - Vuelta, A. B.

AU - Fernández-Nebro, A.

AU - Ordóñez-Cañizares, M. C.

AU - Fernández-Gutiérrez, B.

AU - Rodríguez-Rodríguez, L.

AU - Escalante, B.

AU - Marí-Alfonso, B.

AU - Sopeña, B.

AU - Gómez-Vaquero, C.

AU - Raya, E.

AU - Grau, E.

AU - Román, J. A.

AU - Vicente, E. F.

AU - de Miguel, E.

AU - López-Longo, F. J.

AU - Martínez, L.

AU - Morado, I. C.

AU - Díaz-López, J. B.

AU - Caminal-Montero, L.

AU - Martínez-Zapico, A.

AU - Narváez, J.

AU - Monfort, J.

AU - Tío, L.

AU - Miranda-Filloy, J. A.

AU - Sánchez-Martín, J.

AU - Alegre-Sancho, J. J.

AU - Sáez-Comet, L.

AU - Pérez-Conesa, M.

AU - Corbera-Bellalta, M.

AU - Ramentol-Sintas, M.

AU - García-Villanueva, M. J.

AU - Guijarro Rojas, M.

AU - Ortego-Centeno, N.

AU - Ríos Fernández, R.

AU - Callejas, J. L.

AU - Sanchez Pernaute, O.

AU - Fanlo Mateo, P.

AU - Blanco, R.

AU - Prieto-González, S.

AU - Martínez-Taboada, V. M.

AU - Soriano, A.

AU - Lunardi, C.

AU - Gianfreda, D.

AU - Santilli, D.

AU - Bonatti, F.

AU - Muratore, F.

AU - Pazzola, G.

AU - Addimanda, O.

AU - Emmi, G.

AU - Ramirez, G. A.

AU - Beretta, L.

AU - Govoni, M.

AU - Cimmino, M. A.

AU - Mesut Onat, A.

AU - Cefle, A.

AU - Yazici, A.

AU - Kısacık, B.

AU - Dalkilic, E.

AU - Seyahi, E.

AU - Fresko, I.

AU - Tunc, E.

AU - Erken, E.

AU - Te Ozer, H.

AU - Aksu, K.

AU - Keser, G.

AU - Ozturk, M. A.

AU - Bıcakcıgil, M.

AU - Duzgun, N.

AU - Karadag, O.

AU - Kiraz, S.

AU - Pamuk, O. N.

AU - Akar, S.

AU - Onen, F.

AU - Akkoc, N.

AU - Kamali, S.

AU - Inanc, M.

AU - Yentür, S. P.

AU - Aydin, S. Z.

AU - Alibaz-Oner, F.

AU - Kaşifoğlu, T.

AU - Cobankara, V.

AU - Ozbalkan, Z.

PY - 2017/3/9

Y1 - 2017/3/9

N2 - Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; OR GCA = 1.19, OR TAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P GCA = 5.52E-04, OR GCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

AB - Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; OR GCA = 1.19, OR TAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P GCA = 5.52E-04, OR GCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.

U2 - https://doi.org/10.1038/srep43953

DO - https://doi.org/10.1038/srep43953

M3 - Article

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 43953

ER -

Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

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