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. 2018 Oct 24:363:k4168.
doi: 10.1136/bmj.k4168.

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

Loes Ca Rutten-Jacobs  1   2 , Susanna C Larsson  3 , Rainer Malik  4 , Kristiina Rannikmäe  5   6 ; MEGASTROKE consortium; International Stroke Genetics Consortium; Cathie L Sudlow  5   6   7 , Martin Dichgans  4   8   9 , Hugh S Markus  2 , Matthew Traylor  2
Affiliations

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

Loes Ca Rutten-Jacobs et al. BMJ. .

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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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; HSM has been paid for delivering educational presentations for AstraZeneca; no other financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Flow of participants through study
Fig 2
Fig 2
Standardised risk of incident stroke according to genetic risk and lifestyle profile. Cox proportional hazards models were adjusted for age and sex, and the genetic risk models included additionally the first 10 principal components of ancestry and genotyping batch
See this image and copyright information in PMC

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