High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci

Title
High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
Authors
전재범
Keywords
GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS; SUSCEPTIBILITY LOCI; GENE-EXPRESSION; MULTIPLE COMMON; CELIAC-DISEASE; POPULATION; METAANALYSIS; VARIANT
Issue Date
2015-03
Publisher
BMJ PUBLISHING GROUP
Citation
ANNALS OF THE RHEUMATIC DISEASES, v. 74, NO 3, Page. 1-8
Abstract
Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p˂5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
URI
http://ard.bmj.com/content/74/3/e13.shorthttp://hdl.handle.net/20.500.11754/22557
ISSN
0003-4967; 1468-2060
DOI
http://dx.doi.org/10.1136/annrheumdis-2013-204749
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE