Genetic Risk, Incident Stroke, and the Benefits of Adhering to a Healthy Lifestyle: Cohort Study of 306 473 UK Biobank Participants

Overview

Journal BMJ

Specialty General Medicine

Date 2018 Oct 26

PMID 30355576

Citations 118

Authors

Loes Ca Rutten-Jacobs

Susanna C Larsson

Rainer Malik

Kristiina Rannikmae

Cathie L Sudlow

Martin Dichgans

Hugh S Markus

Matthew Traylor

Affiliations

Soon will be listed here.

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 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/m, 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. 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. 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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References

Touze E, Rothwell P . Sex differences in heritability of ischemic stroke: a systematic review and meta-analysis. Stroke. 2007; 39(1):16-23. DOI: 10.1161/STROKEAHA.107.484618. View

OConnell J, Sharp K, Shrine N, Wain L, Hall I, Tobin M . Haplotype estimation for biobank-scale data sets. Nat Genet. 2016; 48(7):817-20. PMC: 4926957. DOI: 10.1038/ng.3583. View

Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J . UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015; 12(3):e1001779. PMC: 4380465. DOI: 10.1371/journal.pmed.1001779. View

Brass L, Isaacsohn J, Merikangas K, ROBINETTE C . A study of twins and stroke. Stroke. 1992; 23(2):221-3. DOI: 10.1161/01.str.23.2.221. View

Abraham G, Havulinna A, Bhalala O, Byars S, De Livera A, Yetukuri L . Genomic prediction of coronary heart disease. Eur Heart J. 2016; 37(43):3267-3278. PMC: 5146693. DOI: 10.1093/eurheartj/ehw450. View

Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A . Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018; 50(4):524-537. PMC: 5968830. DOI: 10.1038/s41588-018-0058-3. View

Von Sarnowski B, Putaala J, Grittner U, Gaertner B, Schminke U, Curtze S . Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the Stroke in Young Fabry Patients study. Stroke. 2012; 44(1):119-25. DOI: 10.1161/STROKEAHA.112.665190. View

. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 385(9963):117-71. PMC: 4340604. DOI: 10.1016/S0140-6736(14)61682-2. View

Colpani V, Baena C, Jaspers L, van Dijk G, Farajzadegan Z, Dhana K . Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis. Eur J Epidemiol. 2018; 33(9):831-845. DOI: 10.1007/s10654-018-0374-z. View

10.

Andersen K, Andersen Z, Olsen T . Age- and gender-specific prevalence of cardiovascular risk factors in 40,102 patients with first-ever ischemic stroke: a Nationwide Danish Study. Stroke. 2010; 41(12):2768-74. DOI: 10.1161/STROKEAHA.110.595785. View

11.

Reeves M, Bushnell C, Howard G, Gargano J, Duncan P, Lynch G . Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol. 2008; 7(10):915-26. PMC: 2665267. DOI: 10.1016/S1474-4422(08)70193-5. View

12.

Larsson S, Akesson A, Wolk A . Primary prevention of stroke by a healthy lifestyle in a high-risk group. Neurology. 2015; 84(22):2224-8. PMC: 4456657. DOI: 10.1212/WNL.0000000000001637. View

13.

Chiuve S, Rexrode K, Spiegelman D, Logroscino G, Manson J, Rimm E . Primary prevention of stroke by healthy lifestyle. Circulation. 2008; 118(9):947-54. PMC: 2730914. DOI: 10.1161/CIRCULATIONAHA.108.781062. View

14.

Traylor M, Rutten-Jacobs L, Holliday E, Malik R, Sudlow C, Rothwell P . Differences in Common Genetic Predisposition to Ischemic Stroke by Age and Sex. Stroke. 2015; 46(11):3042-7. PMC: 4617282. DOI: 10.1161/STROKEAHA.115.009816. View

15.

Myint P, Luben R, Wareham N, Bingham S, Khaw K . Combined effect of health behaviours and risk of first ever stroke in 20,040 men and women over 11 years' follow-up in Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): prospective population study. BMJ. 2009; 338:b349. PMC: 2645849. DOI: 10.1136/bmj.b349. View

16.

Rutten-Jacobs L, Tozer D, Duering M, Malik R, Dichgans M, Markus H . Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia. Stroke. 2018; 49(6):1340-1347. PMC: 5976227. DOI: 10.1161/STROKEAHA.118.020811. View

17.

Traylor M, Rutten-Jacobs L, Thijs V, Holliday E, Levi C, Bevan S . Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke. Stroke. 2016; 47(5):1174-9. PMC: 4839546. DOI: 10.1161/STROKEAHA.115.011625. View

18.

Khera A, Emdin C, Drake I, Natarajan P, Bick A, Cook N . Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med. 2016; 375(24):2349-2358. PMC: 5338864. DOI: 10.1056/NEJMoa1605086. View

19.

Larsson S, Akesson A, Wolk A . Healthy diet and lifestyle and risk of stroke in a prospective cohort of women. Neurology. 2014; 83(19):1699-704. PMC: 4239835. DOI: 10.1212/WNL.0000000000000954. View

20.

Fava C, Sjogren M, Olsson S, Lovkvist H, Jood K, Engstrom G . A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case-control study. Eur J Hum Genet. 2014; 23(7):969-74. PMC: 4351890. DOI: 10.1038/ejhg.2014.212. View