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Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans
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Sep 15 2017
Source: J Rheumatol. 44(11):1652-1658.
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Alternative Title:J Rheumatol
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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.
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Pubmed ID:28916551
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Pubmed Central ID:PMC5668168
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