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 ε4 was associated with all-cause dementia in a dose-dependent fashion (Case N = 614, Control N = 50,490; APOE ε4/ε4: Hazard Ratio 2.7, P < 0.0001; APOE ε4/ε3: 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 ε4 was also associated with elevated triglycerides and Low Density Lipoprotein (LDL) cholesterol.

DISCUSSION APOE ε4 - the major genetic risk factor for sporadic dementia in European-ancestry populations - has a similar impact on dementia risk in British South Asians.

The authors have declared no competing interest.

BMJ is supported by a Guarantors of Brain post-doctoral fellowship award and an NIHR Clinical Lectureship. AC is funded by the National Institute for Health and Care Research (NIHR - ref: NIHR203373). This work was supported by an Alzheimers Research UK (ARUK) London Network Centre Pump Prime funding award. SW is supported by the Global Parkinsons Genetics Program (GP2). GP2 is funded by the Aligning Science Across Parkinsons (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinsons Research (https://gp2.org).

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All participants provided informed, written consent. A favourable ethical opinion for the main Genes & Health research study was granted by NRES Committee London - South East (reference 14/LO/1240) on 16 Sept 2014. Queen Mary University of London is the Sponsor, and Data Controller.

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