Genome-wide Association Study of Radiographic Knee Osteoarthritis in North American Caucasians

Details

• Alternative Title:
  Arthritis Rheumatol
• Personal Author:
  Yau, Michelle S. ; Yerges-Armstrong, Laura M. ; Liu, Youfang ; Lewis, Cora E. ; Duggan, David J. ; Renner, Jordan B. ; Torner, James ; Felson, David T. ; McCulloch, Charles E. ; Kwoh, C. Kent ; Nevitt, Michael C. ; Hochberg, Marc C. ; Mitchell, Braxton D. ; Jordan, Joanne M. ; Jackson, Rebecca D.
• Description:
  Objective
  
  A major barrier to genetic studies of OA is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically-defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from four well-characterized North American cohorts, and replication analysis of published OA loci.
  
  Methods
  
  We performed meta-analysis using a two-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definitive osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and Genetics of Osteoarthritis Study. We genotyped lead meta-analysis variants (P-value<1×10−4) from Stage 1 and tested the association between these variants and knee OA. We then combined results from all cohorts in a meta-analysis.
  
  Results
  
  Lead variants from Stage 1, representing 49 unique loci, were analyzed in Stage 2; none met genome-wide significance in the combined analysis of Stage 1 and 2. We validated one locus with nominal significance (P-value<0.05), which was also our top finding in the combined meta-analysis: rs4867568 (LSP1P3, OR[95% CI]=0.84[0.79–0.91], P-value=3.02×10−6). We observed nominally significant associations (P-value<0.05) with two published OA loci: rs143383 (GDF5, OR[95% CI]=1.12[1.04–1.21], P-value=2.13×10−3) and rs1558902 (FTO, OR[95% CI]=1.10[1.02–1.18], P-value=0.01).
  
  Conclusion
  
  These findings provide suggestive evidence for a novel knee OA locus and confirm previously published associations in GDF5 and FTO.
  
  
• Subjects:
  Aged Arthrography Case-Control Studies Female Genome-Wide Association Study Humans Male Middle Aged Osteoarthritis, Knee White People
• Source:
  Arthritis Rheumatol. 69(2):343-351.
• Pubmed ID:
  27696742
• Pubmed Central ID:
  PMC5274579
• Document Type:
  Journal Article
• Funding:
  RC2 AR058950/AR/NIAMS NIH HHS/United States ; P60 AR049465/AR/NIAMS NIH HHS/United States ; U01 DP006266/DP/NCCDPHP CDC HHS/United States ; P60 AR030701/AR/NIAMS NIH HHS/United States ; N01AR22260/AR/NIAMS NIH HHS/United States ; N01AR22262/AR/NIAMS NIH HHS/United States ; U01 AG018947/AG/NIA NIH HHS/United States ; T32 AG000262/AG/NIA NIH HHS/United States ; U01 AG019069/AG/NIA NIH HHS/United States ; RA/ARRA NIH HHS/United States ; U01 AG018820/AG/NIA NIH HHS/United States ; N01AR22261/AR/NIAMS NIH HHS/United States ; P30 DK072488/DK/NIDDK NIH HHS/United States ; U01 AG018832/AG/NIA NIH HHS/United States ; T32 AG023480/AG/NIA NIH HHS/United States ; R01 AG028359/AG/NIA NIH HHS/United States ; N01AR22259/AR/NIAMS NIH HHS/United States ; N01AR22258/AR/NIAMS NIH HHS/United States
• Place as Subject:
  North America
• Volume:
  69
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:095e18845010e94553202c1a6de6e7c01f4a2b68fcb9d1807c51c5c45c36c3c8
• Download URL:
  https://stacks.cdc.gov/view/cdc/52618/cdc_52618_DS1.pdf
• File Type:
  [PDF - 355.03 KB ]