PMID- 28407095 OWN - NLM STAT- MEDLINE DCOM- 20170925 LR - 20221207 IS - 1462-0332 (Electronic) IS - 1462-0324 (Print) IS - 1462-0324 (Linking) VI - 56 IP - 8 DP - 2017 Aug 1 TI - Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study. PG - 1282-1292 LID - 10.1093/rheumatology/kex048 [doi] AB - 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 x 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 x 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 x 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 x 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 x 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. CI - (c) The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. FAU - Traylor, Matthew AU - Traylor M AD - Department of Medical and Molecular Genetics, King's College London. FAU - Curtis, Charles AU - Curtis C AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Patel, Hamel AU - Patel H AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Breen, Gerome AU - Breen G AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Hyuck Lee, Sang AU - Hyuck Lee S AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Xu, Xiaohui AU - Xu X AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Newhouse, Stephen AU - Newhouse S AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Dobson, Richard AU - Dobson R AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Steer, Sophia AU - Steer S AD - Department of Rheumatology, King's College Hospital. FAU - Cope, Andrew P AU - Cope AP AD - Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London. FAU - Markus, Hugh S AU - Markus HS AD - Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, UK. FAU - Lewis, Cathryn M AU - Lewis CM AD - Department of Medical and Molecular Genetics, King's College London. AD - SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London. FAU - Scott, Ian C AU - Scott IC AD - Department of Medical and Molecular Genetics, King's College London. AD - Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, London. AD - Department of Rheumatology, Haywood Hospital, Burslem, UK. AD - Research Institute for Primary Care & Health Sciences, Keele University, Staffordshire, UK. LA - eng GR - 20525/VAC_/Versus Arthritis/United Kingdom GR - 076113/WT_/Wellcome Trust/United Kingdom GR - 19739/VAC_/Versus Arthritis/United Kingdom GR - 171/ALZS_/Alzheimer's Society/United Kingdom GR - 085475/WT_/Wellcome Trust/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - 090355/WT_/Wellcome Trust/United Kingdom GR - G1001516/MRC_/Medical Research Council/United Kingdom PT - Journal Article PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Epitopes) RN - 0 (HLA Antigens) SB - IM MH - Adult MH - Aged MH - Alcohol Drinking/adverse effects MH - Arthritis, Rheumatoid/*ethnology/*genetics MH - Asian People/ethnology/genetics MH - Black People/ethnology/*genetics MH - Case-Control Studies MH - Epitopes/analysis MH - Female MH - Gene-Environment Interaction MH - Genetic Predisposition to Disease/*ethnology MH - Genotype MH - HLA Antigens/analysis MH - Haplotypes MH - Humans MH - Logistic Models MH - Male MH - Middle Aged MH - Odds Ratio MH - Risk Factors MH - Smoking/adverse effects MH - United Kingdom MH - White People/ethnology/*genetics PMC - PMC5638023 OTO - NOTNLM OT - African continental ancestry group OT - arthritis OT - genetic susceptibility OT - rheumatoid OT - smoking EDAT- 2017/04/14 06:00 MHDA- 2017/09/26 06:00 PMCR- 2017/04/12 CRDT- 2017/04/14 06:00 PHST- 2016/04/20 00:00 [received] PHST- 2017/04/14 06:00 [pubmed] PHST- 2017/09/26 06:00 [medline] PHST- 2017/04/14 06:00 [entrez] PHST- 2017/04/12 00:00 [pmc-release] AID - 3604846 [pii] AID - kex048 [pii] AID - 10.1093/rheumatology/kex048 [doi] PST - ppublish SO - Rheumatology (Oxford). 2017 Aug 1;56(8):1282-1292. doi: 10.1093/rheumatology/kex048.