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

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Original languageEnglish
Pages (from-to)1282–1292
JournalRheumatology
Volume56
Issue number8
Early online date12 Apr 2017
DOIs
StatePublished - 1 Aug 2017

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Abstract

Objectives: We evaluated whether genetic and environmental factors associated with rheumatoid arthritis (RA) in European and Asian ancestry populations also associate 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 at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic-Genotyping-Array) and HLA alleles imputed. The following European/Asian RA susceptibility factors were tested: (1) 99 genome-wide loci combined into a genetic risk score (GRS); (2) HLA region (20 haplotypes; shared epitope (SE)); (3) smoking; (4) 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 associated with RA in African ancestry individuals. The GRS provided an odds ratio (OR) for RA of 1.53 (95% CI 1.31–1.79; P=1.3x10-754 ). HLA haplotype ORs in European and African ancestry individuals were highly correlated (r=0.83; 95% CI 0.56- 0.94; P=1.1x10-4). Ever-smoking increased (OR 2.36; 95% CI 1.46-3.82; P=4.6x10-456 ) and drinking alcohol reduced (OR 0.34; 95% CI 0.20-0.56; P=2.7x10-5) RA risk in 57 African ancestry individuals. The SE associated with erosions (OR 2.61; 95% CI 1.36–5.01; P=3.9x10-358 ).

Conclusions: 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.

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