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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.

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.

SUBMITTER: Rutten-Jacobs LC

PROVIDER: S-EPMC6199557 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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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.

Rutten-Jacobs Loes Ca LC Larsson Susanna C SC Malik Rainer R Rannikmäe Kristiina K Sudlow Cathie L CL Dichgans Martin M Markus Hugh S HS Traylor Matthew M

BMJ (Clinical research ed.) 20181024

<h4>Objective</h4>To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.<h4>Design</h4>Prospective population based cohort study.<h4>Setting</h4>UK Biobank Study, UK.<h4>Participants</h4>306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.<h4>Main outcome measure</h4>Hazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was co ...[more]

PMID: 30355576

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Project description:BackgroundWorldwide, the prevalence of dementia is increasing and diet as a modifiable factor could play a role. Meat consumption has been cross-sectionally associated with dementia risk, but specific amounts and types related to risk of incident dementia remain poorly understood.ObjectiveWe aimed to investigate associations between meat consumption and risk of incident dementia in the UK Biobank cohort.MethodsMeat consumption was estimated using a short dietary questionnaire at recruitment and repeated 24-h dietary assessments. Incident all-cause dementia comprising Alzheimer disease (AD) and vascular dementia (VD) was identified by electronic linkages to hospital and mortality records. HRs for each meat type in relation to each dementia outcome were estimated in Cox proportional hazard models. Interactions between meat consumption and the apolipoprotein E (APOE) ε4 allele were additionally explored.ResultsAmong 493,888 participants included, 2896 incident cases of all-cause dementia, 1006 cases of AD, and 490 cases of VD were identified, with mean ± SD follow-up of 8 ± 1.1 y. Each additional 25 g/day intake of processed meat was associated with increased risks of incident all-cause dementia (HR: 1.44; 95% CI: 1.24, 1.67; P-trend < 0.001) and AD (HR: 1.52; 95% CI: 1.18, 1.96; P-trend = 0.001). In contrast, a 50-g/d increment in unprocessed red meat intake was associated with reduced risks of all-cause dementia (HR: 0.81; 95% CI: 0.69, 0.95; P-trend = 0.011) and AD (HR: 0.70; 95% CI: 0.53, 0.92; P-trend = 0.009). The linear trend was not significant for unprocessed poultry and total meat. Regarding incident VD, there were no statistically significant linear trends identified, although for processed meat, higher consumption categories were associated with increased risks. The APOE ε4 allele increased dementia risk by 3 to 6 times but did not modify the associations with diet significantly.ConclusionThese findings highlight processed-meat consumption as a potential risk factor for incident dementia, independent of the APOE ε4 allele.

Project description:Background/objectivesDelirium is common in older adults, especially following hospitalization. Because low vitamin D levels may be associated with increased delirium risk, we aimed to determine the prognostic value of blood vitamin D levels, extending our previous genetic analyses of this relationship.DesignProspective cohort analysis.SettingCommunity-based cohort study of adults from 22 cities across the United Kingdom (the UK Biobank).ParticipantsAdults aged 60 and older by the end of follow-up in the linked hospital inpatient admissions data, up to 14 years after baseline (n = 351,320).MeasurementsAt baseline, serum vitamin D (25-OH-D) levels were measured. We used time-to-event models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D deficiency and incident hospital-diagnosed delirium, adjusted for age, sex, assessment month, assessment center, and ethnicity. We performed Mendelian randomization genetic analysis in European participants to further investigate vitamin D and delirium risk.ResultsA total of 3,634 (1.03%) participants had at least one incident hospital-diagnosed delirium episode. Vitamin D deficiency (<25 nmol/L) predicted a large incidence in delirium (HR = 2.49; 95% CI = 2.24-2.76; P = 3*10-68 , compared with >50 nmol/L). Increased risk was not limited to the deficient group: insufficient levels (25-50 nmol/L) were also at increased risk (HR = 1.38; 95% CI = 1.28-1.49; P = 4*10-18 ). The association was independent of calcium levels, hospital-diagnosed fractures, dementia, and other relevant cofactors. In genetic analysis, participants carrying more vitamin D-increasing variants had a reduced likelihood of incident delirium diagnosis (HR = .80 per standard deviation increase in genetically instrumented vitamin D: .73-.87; P = 2*10-7 ).ConclusionProgressively lower vitamin D levels predicted increased risks of incident hospital-diagnosed delirium, and genetic evidence supports a shared causal pathway. Because low vitamin D levels are simple to detect and inexpensive and safe to correct, an intervention trial to confirm these results is urgently needed.

Project description:ImportanceGenetic and lifestyle factors both contribute to the risk of developing cardiovascular disease, but whether poor health behaviors are associated with similar increases in risk among individuals with low, intermediate, or high genetic risk is unknown.ObjectiveTo investigate the association of combined health behaviors and factors within genetic risk groups with coronary artery disease, atrial fibrillation, stroke, hypertension, and type 2 diabetes as well as to investigate the interactions between genetic risk and lifestyle.Design, setting, and participantsThe UK Biobank cohort study includes more than 500?000 participants aged 40 to 70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. A total of 339?003 unrelated individuals of white British descent with available genotype and matching genetic data and reported sex were included in this study from the UK Biobank population-based sample. Individuals were included in the analyses of 1 or more new-onset diseases. Data were analyzed from April 2006 to March 2015.Main outcomes and measuresRisks of new-onset cardiovascular disease and diabetes associated with genetic risk and combined health behaviors and factors. Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2-4), or high (quintile 5). Within each genetic risk group, the risks of incident events associated with ideal, intermediate, or poor combined health behaviors and factors were investigated and compared with low genetic risk and ideal lifestyle.ResultsOf 339?003 individuals, 181?702 (53.6%) were female, and the mean (SD) age was 56.86 (7.99) years. During follow-up, 9771 of 325?133 participants (3.0%) developed coronary artery disease, 7095 of 333?637 (2.1%) developed atrial fibrillation, 3145 of 332?971 (0.9%) developed stroke, 11?358 of 234?651 (4.8%) developed hypertension, and 4379 of 322?014 (1.4%) developed diabetes. Genetic risk and lifestyle were independent predictors of incident events, and there were no interactions for any outcome. Compared with ideal lifestyle in the low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 4.54 (95% CI, 3.72-5.54) for coronary artery disease, 5.41 (95% CI, 4.29-6.81) for atrial fibrillation, 4.68 (95% CI, 3.85-5.69) for hypertension, 2.26 (95% CI, 1.63-3.14) for stroke, and 15.46 (95% CI, 10.82-22.08) for diabetes in the high genetic risk group.Conclusions and relevanceIn this large contemporary population, genetic composition and combined health behaviors and factors had a log-additive effect on the risk of developing cardiovascular disease. The relative effects of poor lifestyle were comparable between genetic risk groups. Behavioral lifestyle changes should be encouraged for all through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on the genetic risk.

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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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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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