Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
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; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Scientific reports - 7(2017) vom: 09. März, Seite 43953 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Carmona, F David [VerfasserIn] |
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| Links: |
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| Themen: |
HLA Antigens |
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| Anmerkungen: |
Date Completed 08.11.2018 Date Revised 13.11.2018 published: Electronic ErratumIn: Sci Rep. 2017 Apr 05;7:46012. - PMID 28378796 Citation Status MEDLINE |
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| doi: |
10.1038/srep43953 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM26968624X |
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| 245 | 1 | 0 | |a Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy |
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| 500 | |a ErratumIn: Sci Rep. 2017 Apr 05;7:46012. - PMID 28378796 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 0 | |a Turkish Takayasu Study Group |e verfasserin |4 aut | |
| 700 | 0 | |a Vasculitis Clinical Research Consortium |e verfasserin |4 aut | |
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