The contribution of apolipoprotein E genetic variation to dementia risk in British South Asians

Abstract INTRODUCTION Understanding the genetic basis of dementia in diverse populations is essential to ensure that efforts to predict, prevent, and treat dementia are equitable. The strongest genetic risk factor for dementia - APOE genotype - has not been assessed in population-scale cohorts of South Asian ancestry. METHODS We analysed data from 51,104 volunteers in the Genes & Health study - a cohort study of British South Asians - who have undergone genotyping and consented for linkage to healthcare records. All-cause dementia was defined using electronic healthcare records. APOE genotypes were defined using phased, imputed genotype data. Cox proportional hazards models were used to assess the relationship between APOE genotype and dementia. Population attributable fractions were calculated for each APOE genotype. RESULTS APOE ε 4 was associated with all-cause dementia in a dose-dependent fashion (Case N = 614, Control N = 50,490; APOE ε 4/ ε 4: Hazard Ratio 2.7, P < 0.0001; APOE ε 4/ ε 3: Hazard Ratio 1.5, P < 0.001). The overall proportion of dementia cases attributable to this allele was 14.2% (95% CI -2.8% - 25.0%). APOE ε 4 was also associated with elevated triglycerides and Low Density Lipoprotein (LDL) cholesterol. DISCUSSION APOE ε 4 - the major genetic risk factor for sporadic dementia in European-ancestry populations - has a similar impact on dementia risk in British South Asians.