Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans

Details

• Alternative Title:
  J Rheumatol
• Personal Author:
  Liu, Youfang ; Yau, Michelle S. ; Yerges-Armstrong, Laura M. ; Duggan, David J. ; Renner, Jordan B. ; Hochberg, Marc C. ; Mitchell, Braxton D. ; Jackson, Rebecca D. ; Jordan, Joanne M.
• Description:
  Objective
  
  The etiology of knee osteoarthritis (OA), the most common form of arthritis, is complex and may differ by race or ethnicity. In recent years, genetic studies have identified multiple genetic variants associated with OA, but nearly all were conducted in European Caucasian and Asian Americans. Few studies have focused on genetics of knee OA in African Americans.
  
  Methods
  
  We performed a genome-wide association study of radiographic knee OA in 1,217 African Americans from two North American cohort studies: 590 subjects from the Johnston County Osteoarthritis Project and 627 subjects from the Osteoarthritis Initiative. Analyses were conducted in each cohort separately and combined in an inverse variance fixed effects meta-analysis, which were then included in pathway analyses. We additionally tested 12 SNPs robustly associated with OA in European Caucasian populations for association in African Americans.
  
  Results
  
  We identified a genome-wide significant variant in LINC01006 (minor allele frequency=12%, p-value=4.11×10−9) that is less common in European Caucasian populations (minor allele frequency < 3%). Five other independent loci reached suggestive significance (p-value < 1×10−6). In pathway analyses, dorsal/ventral neural tube patterning and iron ion transport pathways were significantly associated with knee OA in African Americans (FDR < 0.05). We found no evidence that previously reported OA susceptibility variants in European Caucasians were associated with knee OA in African Americans.
  
  Conclusion
  
  These results highlight differences in the genetic architecture of knee OA between African American and European Caucasians, which underscores the need to include more diverse populations in OA genetics studies.
  
  
• Subjects:
  Aged Alleles Black Or African American Female Gene Frequency Genetic Predisposition To Disease Genotype Humans Knee Joint Male Middle Aged Osteoarthritis, Knee Polymorphism, Single Nucleotide RNA, Long Noncoding Tomography, X-Ray Computed White People

  More +
• Source:
  J Rheumatol. 44(11):1652-1658
• Pubmed ID:
  28916551
• Pubmed Central ID:
  PMC5668168
• Document Type:
  Journal Article
• Funding:
  RC2 AR058950/AR/NIAMS NIH HHSUnited States/ ; P60 AR049465/AR/NIAMS NIH HHSUnited States/ ; U01 DP006266/DP/NCCDPHP CDC HHSUnited States/ ; P60 AR030701/AR/NIAMS NIH HHSUnited States/ ; P30 AG028747/AG/NIA NIH HHSUnited States/ ; T32 AG000262/AG/NIA NIH HHSUnited States/ ; N01AR22261/AR/NIAMS NIH HHSUnited States/ ; P30 DK072488/DK/NIDDK NIH HHSUnited States/ ; N01 AR022261/AR/NIAMS NIH HHSUnited States/ ; T32 AG023480/AG/NIA NIH HHSUnited States/ ; N01 AR022259/AR/NIAMS NIH HHSUnited States/ ; N01 AR022258/AR/NIAMS NIH HHSUnited States/ ; N01 AR022262/AR/NIAMS NIH HHSUnited States/ ; N01 AR022260/AR/NIAMS NIH HHSUnited States/
• Volume:
  44
• Issue:
  11
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:3f9c115889c97ced49da72fbedec8b58d82f06c3ec04f988a583f8a7bf68a435
• Download URL:
  https://stacks.cdc.gov/view/cdc/52620/cdc_52620_DS1.pdf
• File Type:
  [PDF - 584.01 KB ]