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


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.

SUBMITTER: Rutten-Jacobs LC 

PROVIDER: S-EPMC6199557 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Rutten-Jacobs Loes Ca LC   Larsson Susanna C SC   Malik Rainer R   Rannikmäe Kristiina K   Sudlow Cathie L CL   Dichgans Martin M   Markus Hugh S HS   Traylor Matthew M  

BMJ (Clinical research ed.) 20181024


<h4>Objective</h4>To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.<h4>Design</h4>Prospective population based cohort study.<h4>Setting</h4>UK Biobank Study, UK.<h4>Participants</h4>306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.<h4>Main outcome measure</h4>Hazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was co  ...[more]

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