TY - JOUR
T1 - Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA
T2 - A meta-analysis of genome-wide association study in a Japanese population
AU - Terao, Chikashi
AU - Ohmura, Koichiro
AU - Kochi, Yuta
AU - Ikari, Katsunori
AU - Okada, Yukinori
AU - Shimizu, Masakazu
AU - Nishina, Naoshi
AU - Suzuki, Akari
AU - Myouzen, Keiko
AU - Kawaguchi, Takahisa
AU - Takahashi, Meiko
AU - Takasugi, Kiyoshi
AU - Murasawa, Akira
AU - Mizuki, Shinichi
AU - Iwahashi, Mitsuhiro
AU - Funahashi, Keiko
AU - Natsumeda, Masamitsu
AU - Furu, Moritoshi
AU - Hashimoto, Motomu
AU - Ito, Hiromu
AU - Fujii, Takao
AU - Ezawa, Kazuhiko
AU - Matsubara, Tsukasa
AU - Takeuchi, Tsutomu
AU - Kubo, Michiaki
AU - Yamada, Ryo
AU - Taniguchi, Atsuo
AU - Yamanaka, Hisashi
AU - Momohara, Shigeki
AU - Yamamoto, Kazuhiko
AU - Mimori, Tsuneyo
AU - Matsuda, Fumihiko
N1 - Publisher Copyright:
© Terao et al.; licensee BioMed Central.
PY - 2015/4/18
Y1 - 2015/4/18
N2 - Introduction: Although susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by genome-wide association studies (GWAS), little is known about the genetic background of ACPA-negative RA. We intended to elucidate genetic background of ACPA-negative RA. Method: We performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, followed by a replication study of the top 35 single nucleotide polymorphisms (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility loci between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed. Results: Rs6904716 in LEMD2 of the human leukocyte antigen (HLA) locus showed a borderline association with ACPA-negative RA (overall p = 5.7 × 10-8), followed by rs6986423 in CSMD1 (p = 2.4 × 10-6) and rs17727339 in FCRL3 (p = 1.4 × 10-5). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations. Conclusion: Many of the susceptibility loci were shared between ACPA-positive and -negative RA.
AB - Introduction: Although susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by genome-wide association studies (GWAS), little is known about the genetic background of ACPA-negative RA. We intended to elucidate genetic background of ACPA-negative RA. Method: We performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, followed by a replication study of the top 35 single nucleotide polymorphisms (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility loci between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed. Results: Rs6904716 in LEMD2 of the human leukocyte antigen (HLA) locus showed a borderline association with ACPA-negative RA (overall p = 5.7 × 10-8), followed by rs6986423 in CSMD1 (p = 2.4 × 10-6) and rs17727339 in FCRL3 (p = 1.4 × 10-5). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations. Conclusion: Many of the susceptibility loci were shared between ACPA-positive and -negative RA.
UR - https://www.scopus.com/pages/publications/84929298327
UR - https://www.scopus.com/pages/publications/84929298327#tab=citedBy
U2 - 10.1186/s13075-015-0623-4
DO - 10.1186/s13075-015-0623-4
M3 - Article
C2 - 25927497
AN - SCOPUS:84929298327
SN - 1478-6354
VL - 17
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 104
ER -