Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants [遗传风险、中风与坚持健康生活方式的益处：基于英国生物库306473名参与者的队列研究]

• 分享：

BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4168 (Published 24 October 2018)
Cite this as: BMJ 2018;363:k4168

Authors
Loes CA Rutten-Jacobs, Susanna C Larsson, Rainer Malik, Kristiina Rannikmäe, Cathie L Sudlow, Martin Dichgans, Hugh S Markus, Matthew Traylor

Abstract
Objective To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.

Design Prospective population based cohort study.

Setting UK Biobank Study, UK.

Participants 306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.

Main outcome measure Hazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10⁻⁵ to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, 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), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10⁻⁸. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10⁻¹³. The association with lifestyle was independent of genetic risk stratums.

Conclusion In this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.