| Title: | Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants |
| Journal: | The BMJ |
| Published: | 24 Oct 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30355576/ |
| DOI: | https://doi.org/10.1136/bmj.k4168 |
| URL: | https://www.bmj.com/content/bmj/363/bmj.k4168.full.pdf |
| Citations: | 209 (85 in last 2 years) as of 8 Aug 2024 |
Publication 12914
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Abstract
OBJECTIVE: To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.</p>
DESIGN: Prospective population based cohort study.</p>
SETTING: UK Biobank Study, UK.</p>
PARTICIPANTS: 306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.</p>
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.</p>
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.</p>
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.</p>
20 Keywords
- Adult
- Aged
- Cerebral Hemorrhage
- Exercise
- Female
- Genetic Predisposition to Disease
- Healthy Lifestyle
- Humans
- Incidence
- Male
- Middle Aged
- Multifactorial Inheritance
- Myocardial Infarction
- Patient Compliance
- Polymorphism, Single Nucleotide
- Prospective Studies
- Risk Factors
- Stroke
- Subarachnoid Hemorrhage
- United Kingdom
10 Authors
- Loes CA Rutten-Jacobs
- Susanna C Larsson
- Rainer Malik
- Kristiina Rannikmäe
- MEGASTROKE consortium
- International Stroke Genetics Consortium
- Cathie L Sudlow
- Martin Dichgans
- Hugh S Markus
- Matthew Traylor
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