RT Journal Article
SR Electronic
T1 Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1652
OP 1658
DO 10.3899/jrheum.161488
VO 44
IS 11
A1 Youfang Liu
A1 Michelle S. Yau
A1 Laura M. Yerges-Armstrong
A1 David J. Duggan
A1 Jordan B. Renner
A1 Marc C. Hochberg
A1 Braxton D. Mitchell
A1 Rebecca D. Jackson
A1 Joanne M. Jordan
YR 2017
UL http://www.jrheum.org/content/44/11/1652.abstract
AB 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 many genetic variants associated with OA, but nearly all the studies were conducted in European whites and Asian Americans. Few studies have focused on the genetics of knee OA in African Americans.Methods. We performed a genome-wide association study of radiographic knee OA in 1217 African Americans from 2 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 metaanalysis, which were then included in pathway analyses. We additionally tested 12 single-nucleotide polymorphisms robustly associated with OA in European white populations for association in African Americans.Results. We identified a genome-wide significant variant in LINC01006 (minor allele frequency 12%; p = 4.11 × 10−9) that is less common in European white populations (minor allele frequency < 3%). Five other independent loci reached suggestive significance (p < 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 (false discovery rate < 0.05). We found no evidence that previously reported OA susceptibility variants in European whites 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 whites. This finding underscores the need to include more diverse populations in OA genetics studies.