Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
نویسندگان
چکیده
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.
منابع مشابه
Corrigendum: Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the mater...
متن کاملBjrd15992 1..12
The respiratory system may be involved in all systemic vasculitides, although with a variable frequency. The aim of our review is to describe radiographic and high-resolution CT (HRCT) findings of pulmonary vasculitides and to correlate radiological findings with pathological results. Lung disease is a common feature of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitide...
متن کاملHealth-Related Quality of Life in Iranian Patients with Thalassemia Major: A Systematic Review and Meta-Analysis
Background: Thalassemia is the most common genetic disorder in Iran. High treatment costs, the use of iron chelators, comorbidities and periodic visits affect the quality of life in these patients. The present study was conducted to assess the quality of life, according to the Short healthy survey (SF-36), in Iranian patients with thalassemia major.Materials and Methods In this meta-analysis, s...
متن کاملPTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus
OBJECTIVES Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine speci...
متن کاملElevated white blood cell counts and risk of metabolic syndrome: a dose-response meta-analysis
Background and Aim: Elevated white blood cell count has been a known risk factor for cardiovascular diseases. Cardiometabolic diseases have some risk factors in common. Therefore, we assessed the association between elevated white blood cell counts and risk of metabolic syndrome using dose-response meta-analysis method. Materials & Methods: We searched for observational studies including white ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2017