ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 409

Pathway Analysis of Genome-Wide Association Studies On Rheumatoid Arthritis

Young Ho Lee1, Sung Jae Choi2, Jong Dae Ji2 and Gwan Gyu Song3, 1Internal Medicine, Rheumatology, Korea University Medical Center, Seoul, South Korea, 2Rheumatology, Korea University Medical Center, Seoul, South Korea, 3Div of Rheum, Dept of Int Med, Korea Univ College of Med, Seoul, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: genomics, polymorphism and rheumatoid arthritis (RA)

  • Tweet
  • Email
  • Print
Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenisis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Genome-wide association studies (GWASs) have been successfully used to identify novel common genetic variants that contribute to susceptibility to complex diseases, but individual GWASs are limited in terms of identifying new loci. Thus, pathway-based analysis is required to identify further new loci that contribute to susceptibility to complex diseases. The aims of this study were to identify candidate causal single nucleotide polymorphisms (SNPs) and candidate causal mechanisms of rheumatoid arthritis (RA) and generate hypothesis for SNP à gene à pathways.

Methods: An meta-analysis dataset of RA GWASs was used that included 2,554,714 SNPs in 5,539 RA cases and 20,169 controls of European descent. ICSNPathway (Identify candidate Causal SNPs and Pathways) analysis was applied to meta-analysis results of the RA GWAS dataset.

Results: ICSNPathway analysis identified 49 candidate causal SNPs and 37 candidate causal pathways. The top 5 candidate causal SNPs, rs1063478 (p = 5.40E-09), rs375256 (p = 3.44E-09), rs365066 (p = 3.60E-30), rs2581 (p = 2.7E-25), and rs1059510 (p = 2.52E-06) were all at human leukocyte antigen (HLA) loci. These candidate causal SNPs and pathways provide 22 hypothetical biological mechanisms. The most strongly associated pathway concerned HLA: rs1063478 (nonsynonymous coding) à HLA-DMA à antigen processing and presentation of peptide antigen. ICSNPathway analysis identified two candidate causal non-HLA SNPs and ten candidate causal pathways, which provided two hypothetical biological mechanisms. First, rs2476601 (nonsynonymous coding [deleterious]) (p = 6.22E-71)  à protein tyrosine phosphatase nonreceptor 22 (PTPN22) à immune response-activation cell surface receptor signaling pathway, and, rs2230926 (nonsynonymous coding) (p = 1.26E-07) à tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) à the CD40L signaling pathway.

Conclusion: The application of ICSNPathway analysis to meta-analysis results of RA GWAS datasets resulted in the identification of candidate causal SNPs and pathways involving HLA-DMA, PTPN22, and TNAIP3 that might contribute to RA susceptibility.


Disclosure:

Y. H. Lee,
None;

S. J. Choi,
None;

J. D. Ji,
None;

G. G. Song,
None.

  • Tweet
  • Email
  • Print

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/pathway-analysis-of-genome-wide-association-studies-on-rheumatoid-arthritis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology