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

Matthew Traylor; Charles Curtis; Hamel Patel; Gerome Breen; Sang Hyuck Lee; Xiaohui Xu; Stephen Newhouse; Richard Dobson; Sophia Steer; Andrew P. Cope; Hugh S. Markus; Cathryn M. Lewis; Ian C. Scott

doi:10.1093/rheumatology/kex048

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

Matthew Traylor, Charles Curtis, Hamel Patel, Gerome Breen, Sang Hyuck Lee, Xiaohui Xu, Stephen Newhouse, Richard Dobson, Sophia Steer, Andrew P. Cope, Hugh S. Markus, Cathryn M. Lewis, Ian C. Scott

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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.

Original language	English
Pages (from-to)	1282–1292
Journal	Rheumatology
Volume	56
Issue number	8
Early online date	12 Apr 2017
DOIs	https://doi.org/10.1093/rheumatology/kex048
Publication status	Published - 1 Aug 2017

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Traylor, M., Curtis, C., Patel, H., Breen, G., Hyuck Lee, S., Xu, X., Newhouse, S., Dobson, R., Steer, S., Cope, A. P., Markus, H. S., Lewis, C. M., & Scott, I. C. (2017). Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study. Rheumatology, 56(8), 1282–1292. https://doi.org/10.1093/rheumatology/kex048

@article{b71b494b9979499080c128b724eef64a,

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

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.",

author = "Matthew Traylor and Charles Curtis and Hamel Patel and Gerome Breen and {Hyuck Lee}, Sang and Xiaohui Xu and Stephen Newhouse and Richard Dobson and Sophia Steer and Cope, {Andrew P.} and Markus, {Hugh S.} and Lewis, {Cathryn M.} and Scott, {Ian C.}",

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doi = "10.1093/rheumatology/kex048",

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Traylor, M , Curtis, C , Patel, H , Breen, G , Hyuck Lee, S , Xu, X , Newhouse, S , Dobson, R , Steer, S , Cope, AP, Markus, HS, Lewis, CM & Scott, IC 2017, 'Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study', Rheumatology, vol. 56, no. 8, pp. 1282–1292. https://doi.org/10.1093/rheumatology/kex048

TY - JOUR

T1 - Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population

T2 - the GENRA case-control study

AU - Traylor, Matthew

AU - Curtis, Charles

AU - Patel, Hamel

AU - Breen, Gerome

AU - Hyuck Lee, Sang

AU - Xu, Xiaohui

AU - Newhouse, Stephen

AU - Dobson, Richard

AU - Steer, Sophia

AU - Cope, Andrew P.

AU - Markus, Hugh S.

AU - Lewis, Cathryn M.

AU - Scott, Ian C.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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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DO - 10.1093/rheumatology/kex048

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JO - Rheumatology

JF - Rheumatology

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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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