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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

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  • MEGASTROKE Consortium
  • International Stroke Genetics Consortium
  • Loes C A Rutten-Jacobs
  • S Larsson
  • Rainer Malik
  • Kristiina Rannikmae
  • Catherine Sudlow
  • Martin Dichgans
  • Hugh S Markus
  • Matthew Traylor

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Original languageEnglish
JournalBritish Medical Journal (BMJ)
Volume363
DOIs
Publication statusPublished - 24 Oct 2018

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.

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