Traylor, M;
Curtis, C;
Patel, H;
Breen, G;
Hyuck Lee, S;
Xu, X;
Newhouse, S;
... Scott, IC; + view all
(2017)
Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.
Rheumatology
, 56
(8)
pp. 1282-1292.
10.1093/rheumatology/kex048.
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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.
| Type: | Article |
|---|---|
| Title: | Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/rheumatology/kex048 |
| Publisher version: | http://dx.doi.org/10.1093/rheumatology/kex048 |
| Language: | English |
| Additional information: | © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | African continental ancestry group, arthritis, genetic susceptibility, rheumatoid, smoking |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1552418 |
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