Skip to main content

Research Repository

Advanced Search

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case - control study

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case - control study Thumbnail


Abstract

Objectives. To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals.

Methods. A case–control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture.

Results. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 -7). HLA haplotype ORs in European and African ancestry individuals were highly correlated (r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 -4). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 -4) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 -5) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 -3).

Conclusion. Gene–environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable.

Citation

(2017). Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case - control study. Rheumatology, 1282-1292. https://doi.org/10.1093/rheumatology/kex048

Acceptance Date Feb 13, 2017
Publication Date Apr 12, 2017
Journal Rheumatology
Print ISSN 1462-0324
Publisher Oxford University Press
Pages 1282-1292
DOI https://doi.org/10.1093/rheumatology/kex048
Keywords arthritis; rheumatoid; African continental ancestry group; genetic susceptibility; smoking
Publisher URL https://doi.org/10.1093/rheumatology/kex048

Files




Downloadable Citations