Details:

Alternative Title:
J Rheumatol
Personal Author:
Liu, Youfang ; Yau, Michelle S. ; Yerges-Armstrong, Laura M. ; Duggan, David J. ; Renner, Jordan B. ; ... More +
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. Less -
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:
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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
Source:
J Rheumatol. 44(11):1652-1658.
Pubmed ID:
28916551
Pubmed Central ID:
PMC5668168
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 ; P30 AG028747/AG/NIA NIH HHS/United States ; ... More +
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 ; P30 AG028747/AG/NIA NIH HHS/United States ; T32 AG000262/AG/NIA NIH HHS/United States ; N01AR22261/AR/NIAMS NIH HHS/United States ; N01 AR022261/AR/WHI NIH HHS/United States ; P30 DK072488/DK/NIDDK NIH HHS/United States ; N01 AR022258/AR/WHI NIH HHS/United States ; T32 AG023480/AG/NIA NIH HHS/United States ; N01 AR022259/AR/WHI NIH HHS/United States ; N01 AR022262/AR/WHI NIH HHS/United States ; N01 AR022260/AR/WHI NIH HHS/United States Less -
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:

Supporting Files

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