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BMJ. 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.

Author information

1
German Center for Neurodegenerative diseases (DZNE), Population Health Sciences, Sigmund-Freud-Strasse 27, 53127 Bonn, Germany.
2
Department of Clinical Neurosciences, Stroke Research Group, University of Cambridge, UK.
3
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
4
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
5
Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
6
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
7
Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
8
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
9
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

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.

PMID:
30355576
PMCID:
PMC6199557
DOI:
10.1136/bmj.k4168
[Indexed for MEDLINE]
Free PMC Article

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.

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