Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants. (24th October 2018)

• Record Type: Journal Article
• Authors: Rutten-Jacobs, Loes CA; Larsson, Susanna C; Malik, Rainer; Rannikmäe, Kristiina; Sudlow, Cathie L; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew
• Is Part Of: BMJ. Volume 363(2018)
• Publication Date: 2018-10-24
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Periodicals; 610
• DOI: 10.1136/bmj.k4168
• Languages: English
• ISSNs: 0007-1447

Abstract

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/m 2, 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.