Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants.

Abstract

Objectives Genetic factors contribute to the risk of stroke. Whether adherence to a healthy lifestyle can attenuate this increased risk is unknown. We evaluated the associations of a polygenic risk score and healthy lifestyle with incident stroke. Design Prospective population-based cohort study Setting UK Biobank Study, United Kingdom Participants 306,473 men and women, aged 40-73 years, requited between 2006 and 2010 Main outcome measure Cox regression was used to estimate hazard ratios for a first stroke. We constructed a polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke at p<1x10-5. We tested this score for association with incident stroke. Adherence to a healthy lifestyle was determined using a score of four factors: no current smoking, healthy diet, body mass index <30 kg/m2 and regular physical exercise. Results During a median follow-up of 7.1 years (2,138,443 person-years), 2,077 incident strokes (1,541 ischaemic stroke, 287 intracerebral haemorrhage and 249 subarachnoid haemorrhage) were ascertained. Risk of incident stroke was 35% higher among individuals at high genetic risk (top tertile of polygenic score) compared with those at low genetic risk (bottom tertile) (HR 1.35, 95% CI 1.21 to 1.50, p=3.9´10-8). Unfavourable lifestyle (0-1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3-4 healthy lifestyle factors) (HR 1.66, 95% CI 1.45 to 1.89, p=1.19´10-13). The association with lifestyle was independent of genetic risk strata. Conclusions In this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasize the benefit of adhering to a healthy lifestyle for the entire population, independent of genetic risk