Identification and Functional Characterization of a Novel Susceptibility Locus for Small Vessel Vasculitis with MPO-ANCA

Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types

EVS Trend File 1981-2017 – Sensitive Dataset

The European Values Study is a large-scale, cross-national and longitudinal survey research program on how Europeans think about family, work, religion, politics, and society. Repeated every nine years in an increasing number of countries, the survey provides insights into the ideas, beliefs, preferences, attitudes, values, and opinions of citizens all over Europe. The EVS Trend File 1981-2017 is constructed from the five EVS waves and covers almost 40 years. In altogether 160 surveys, more than 224.000 respondents from 48 countries/regions were interviewed. It is based on the updated data of the EVS Longitudinal Data File 1981-2008 (v.3.1.0) and the current EVS 2017 Integrated Dataset (v.5.0.0). For the EVS Trend File, a Restricted-Use File (ZA7504) is available in addition to the (factually anonymised) Scientific-Use File (ZA7503). The EVS Trend File – Sensitive Dataset (ZA7504) is provided as an add-on file. In addition to a small set of admin and protocol variables needed to merge with the SUF data, the Sensitive Dataset contains the following variables that could not be included in the scientific-use file due to their sensitive nature: W005_3 Job profession/industry (3-digit ISCO88) - spouse/partner EVS 2008W005_3_01 Job profession/industry (3-digit ISCO08) - spouse/partner EVS 2017W005_4 Job profession/industry (4-digit ISCO88) - spouse/partner EVS 2008X035_3 Job profession/industry (3-digit ISCO88) – respondent EVS 1999, EVS 2008 X035_3_01 Job profession/industry (3-digit ISCO08) - respondent EVS 2017X035_4 Job profession/industry (4-digit ISCO88) – respondent EVS 1999, EVS 2008 x048c_n3 Region where the interview was conducted (NUTS-3): NUTS version 2006 EVS 2008X048J_N3 Region where the interview was conducted (NUTS-3): NUTS version 2016 EVS 2017X049 Size of town (8 categories) EVS 2008, EVS 2017 Detailed information on the anonymization process in the EVS Trend File is provided in the EVS Trend File Variable Report