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

BMJ ◽  
2018 ◽  
pp. k4168 ◽  
Author(s):  
Loes CA Rutten-Jacobs ◽  
Susanna C Larsson ◽  
Rainer Malik ◽  
Kristiina Rannikmäe ◽  
Cathie L Sudlow ◽  
...  
Keyword(s):  
Cohort Study ◽  
Risk Score ◽  
Genetic Risk ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Increased Risk

AbstractObjectiveTo evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.DesignProspective population based cohort study.SettingUK Biobank Study, UK.Participants306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.Main outcome measureHazard 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<1×10−5to 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.ResultsDuring 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.ConclusionIn 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.

Genetic Risk, a Healthy Lifestyle, and Type 2 Diabetes: the Dongfeng-Tongji Cohort Study

2020 ◽  
Vol 105 (4) ◽  
pp. 1242-1250
Author(s):  
Xu Han ◽  
Yue Wei ◽  
Hua Hu ◽  
Jing Wang ◽  
Zhaoyang Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Risk Score ◽  
Genetic Risk ◽  
Healthy Lifestyle ◽  
Genetic Risk Score ◽  
Lifestyle Factors ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Polygenic Risk Score ◽  
Weighted Genetic Risk Score

Abstract Objective The objective of this study is to examine whether healthy lifestyle could reduce diabetes risk among individuals with different genetic profiles. Design A prospective cohort study with a median follow-up of 4.6 years from the Dongfeng-Tongji cohort was performed. Participants A total of 19 005 individuals without diabetes at baseline participated in the study. Main Variable Measure A healthy lifestyle was determined based on 6 factors: nonsmoker, nondrinker, healthy diet, body mass index of 18.5 to 23.9 kg/m2, waist circumference less than 85 cm for men and less than 80 cm for women, and higher level of physical activity. Associations of combined lifestyle factors and incident diabetes were estimated using Cox proportional hazard regression. A polygenic risk score of 88 single-nucleotide polymorphisms previously associated with diabetes was constructed to test for association with diabetes risk among 7344 individuals, using logistic regression. Results A total of 1555 incident diabetes were ascertained. Per SD increment of simple and weighted genetic risk score was associated with a 1.39- and 1.34-fold higher diabetes risk, respectively. Compared with poor lifestyle, intermediate and ideal lifestyle were reduced to a 23% and 46% risk of incident diabetes, respectively. Association of lifestyle with diabetes risk was independent of genetic risk. Even among individuals with high genetic risk, intermediate and ideal lifestyle were separately associated with a 29% and 49% lower risk of diabetes. Conclusion Genetic and combined lifestyle factors were independently associated with diabetes risk. A healthy lifestyle could lower diabetes risk across different genetic risk categories, emphasizing the benefit of entire populations adhering to a healthy lifestyle.

scholarly journals Diet quality indices, genetic risk and risk of cardiovascular disease and mortality: a longitudinal analysis of 77 004 UK Biobank participants

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e045362
Author(s):  
Katherine M Livingstone ◽  
Gavin Abbott ◽  
Steven J Bowe ◽  
Joey Ward ◽  
Catherine Milte ◽  
...  
Keyword(s):  
Risk Score ◽  
Diet Quality ◽  
Genetic Risk ◽  
Lower Risk ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Quality Indices ◽  
Polygenic Risk ◽  
All Cause Mortality ◽  
Cvd Mortality

ObjectivesTo examine associations of three diet quality indices and a polygenic risk score with incidence of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke.DesignProspective cohort study.SettingUK Biobank, UK.Participants77 004 men and women (40–70 years) recruited between 2006 and 2010.Main outcome measuresA polygenic risk score was created from 300 single nucleotide polymorphisms associated with CVD. Cox proportional HRs were used to estimate independent effects of diet quality and genetic risk on all-cause mortality, CVD mortality, MI and stroke risk. Dietary intake (Oxford WebQ) was used to calculate Recommended Food Score (RFS), Healthy Diet Indicator (HDI) and Mediterranean Diet Score (MDS).ResultsNew all-cause (n=2409) and CVD (n=364) deaths and MI (n=1141) and stroke (n=748) events were identified during mean follow-ups of 7.9 and 7.8 years, respectively. The adjusted HR associated with one-point higher RFS for all-cause mortality was 0.96 (95% CI: 0.94 to 0.98), CVD mortality was 0.94 (95% CI: 0.90 to 0.98), MI was 0.97 (95% CI: 0.95 to 1.00) and stroke was 0.94 (95% CI: 0.91 to 0.98). The adjusted HR for all-cause mortality associated with one-point higher HDI and MDS was 0.97 (95% CI: 0.93 to 0.99) and 0.95 (95% CI: 0.91 to 0.98), respectively. The adjusted HR associated with one-point higher MDS for stroke was 0.93 (95% CI: 0.87 to 1.00). There was little evidence of associations between HDI and risk of CVD mortality, MI or stroke. There was evidence of an interaction between diet quality and genetic risk score for MI.ConclusionHigher diet quality predicted lower risk of all-cause mortality, independent of genetic risk. Higher RFS was also associated with lower risk of CVD mortality and MI. These findings demonstrate the benefit of following a healthy diet, regardless of genetic risk.

scholarly journals Polygenic Risk Score Prediction for Endometriosis

2021 ◽  
Vol 3 ◽  
Author(s):  
Kirstine Kloeve-Mogensen ◽  
Palle Duun Rohde ◽  
Simone Twisttmann ◽  
Marianne Nygaard ◽  
Kristina Magaard Koldby ◽  
...  
Keyword(s):  
Risk Score ◽  
Genome Wide Association Study ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Standard Deviation Increase ◽  
Polygenic Risk ◽  
Clinical Risk ◽  
Risk Variants ◽  
Increased Risk ◽  
The Uk

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment. The aim of this work was to investigate the discriminative ability of a polygenic risk score (PRS) for endometriosis using three different cohorts: surgically confirmed cases from the Western Danish endometriosis referral Center (249 cases, 348 controls), cases identified from the Danish Twin Registry (DTR) based on ICD-10 codes from the National Patient Registry (140 cases, 316 controls), and replication analysis in the UK Biobank (2,967 cases, 256,222 controls). Patients with adenomyosis from the DTR (25 cases) and from the UK Biobank (1,883 cases) were included for comparison. The PRS was derived from 14 genetic variants identified in a published genome-wide association study with more than 17,000 cases. The PRS was associated with endometriosis in surgically confirmed cases [odds ratio (OR) = 1.59, p = 2.57× 10−7] and in cases from the DTR biobank (OR = 1.50, p = 0.0001). Combining the two Danish cohorts, each standard deviation increase in PRS was associated with endometriosis (OR = 1.57, p = 2.5× 10−11), as well as the major subtypes of endometriosis; ovarian (OR = 1.72, p = 6.7× 10−5), infiltrating (OR = 1.66, p = 2.7× 10−9), and peritoneal (OR = 1.51, p = 2.6 × 10−3). These findings were replicated in the UK Biobank with a much larger sample size (OR = 1.28, p &lt; 2.2× 10−16). The PRS was not associated with adenomyosis, suggesting that adenomyosis is not driven by the same genetic risk variants as endometriosis. Our results suggest that a PRS captures an increased risk of all types of endometriosis rather than an increased risk for endometriosis in specific locations. Although the discriminative accuracy is not yet sufficient as a stand-alone clinical utility, our data demonstrate that genetics risk variants in form of a simple PRS may add significant new discriminatory value. We suggest that an endometriosis PRS in combination with classical clinical risk factors and symptoms could be an important step in developing an urgently needed endometriosis risk stratification tool.

scholarly journals Polygenic risk score, healthy lifestyles, and risk of incident depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi Cao ◽  
Hongxi Yang ◽  
Yixuan Ye ◽  
Yuan Zhang ◽  
Shu Li ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Healthy Lifestyles ◽  
Current Smoking ◽  
Polygenic Risk ◽  
High Genetic Risk ◽  
Moderate Alcohol Intake ◽  
The Uk

AbstractGenetic factors increase the risk of depression, but the extent to which this can be offset by modifiable lifestyle factors is unknown. We investigated whether a combination of healthy lifestyles is associated with lower risk of depression regardless of genetic risk. Data were obtained from the UK Biobank and consisted of 339,767 participants (37–73 years old) without depression between 2006 and 2010. Genetic risk was categorized as low, intermediate, or high according to polygenic risk score for depression. A combination of healthy lifestyles factors—including no current smoking, regular physical activity, a healthy diet, moderate alcohol intake and a body mass index <30 kg/m2—was categorized into favorable, intermediate, and unfavorable lifestyles. The risk of depression was 22% higher among those at high genetic risk compared with those at low genetic risk (HR = 1.22, 95% CI: 1.14–1.30). Participants with high genetic risk and unfavorable lifestyle had a more than two-fold risk of incident depression compared with low genetic risk and favorable lifestyle (HR = 2.18, 95% CI: 1.84–2.58). There was no significant interaction between genetic risk and lifestyle factors (P for interaction = 0.69). Among participants at high genetic risk, a favorable lifestyle was associated with nearly 50% lower relative risk of depression than an unfavorable lifestyle (HR = 0.51, 95% CI: 0.43–0.60). We concluded that genetic and lifestyle factors were independently associated with risk of incident depression. Adherence to healthy lifestyles may lower the risk of depression regardless of genetic risk.

scholarly journals Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank

2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Jennifer L. Halford ◽  
Lu-Chen Weng ◽  
Seung Hoan Choi ◽  
Sean J. Jurgens ◽  
Valerie N. Morrill ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alcohol Consumption ◽  
Risk Score ◽  
Alcohol Intake ◽  
Hazard Ratio ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Acceptable Range ◽  
Increased Risk

Background: Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We assessed the association between alcohol intake, polygenic predisposition to AF, and incident AF in the UK Biobank, a prospective cohort study. Methods: In 376 776 UK Biobank participants enrolled between 2006 and 2010, we tested alcohol consumption (stratified by the Centers of Disease Control and Prevention acceptable range of ≤98 g/wk for women or ≤196 g/wk for men; and as a continuous variable) and an AF polygenic risk score for association with incident AF. Results: Among participants (47.5% male, mean age 56.9 years), 6293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio, 1.10 [95% CI, 1.05–1.16] for intake above an acceptable range; hazard ratio, 1.04 per 100 g/wk [95% CI, 1.02–1.06]). An AF polygenic risk score was associated with AF (hazard ratio, 1.38 per SD [95% CI, 1.35–1.41]). In models including both alcohol and the AF polygenic risk score, each remained associated with AF. The 5-year cumulative risk of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI, 2.07–2.59), compared with 0.69% (95% CI, 0.58–0.80) for those with alcohol intake within an acceptable range and in the lowest decile of polygenic risk. Conclusions: Alcohol consumption is associated with increased risk of AF across a range of polygenic predisposition to AF and adds to inherited and clinical predisposition to increase AF susceptibility. Preventive efforts focused on minimizing alcohol intake may be broadly applicable.

scholarly journals Parkinson’s disease determinants, prediction and gene-environment interactions in the UK Biobank

2020 ◽  
Author(s):  
Benjamin M. Jacobs ◽  
Daniel Belete ◽  
Jonathan P Bestwick ◽  
Cornelis Blauwendraat ◽  
Sara Bandres-Ciga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Risk Score ◽  
Genetic Risk ◽  
Positive Family History ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Gene Environment ◽  
History Of

AbstractObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate existing risk prediction algorithms and the impact of including addition genetic risk on the performance of prediction.MethodsWe identified individuals with incident PD diagnoses (n=1276) and unmatched controls (n=500,406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. A polygenic risk score (PRS) was constructed and used to examine gene-environment interactions. The PRS was also incorporated into a previously-developed prediction algorithm for finding incident cases.ResultsStrong evidence of association (Pcorr<0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, and daytime somnolence, and novel associations with epilepsy and earlier menarche. Individuals with the highest 10% of PRS scores had increased risk of PD (OR=3.30, 95% CI 2.57-4.24) compared to the lowest risk decile. Higher PRS scores were associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm improved model performance (Nagelkerke pseudo-R2 0.0053, p=6.87×10−14). We found evidence of interaction between the PRS and diabetes.InterpretationHere we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity and predictive power of a polygenic risk score, and to demonstrate a novel gene-environment interaction, whereby the effect of diabetes on PD risk appears to depend on prior genetic risk for PD.

Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012263
Author(s):  
Xiangfeng Lu ◽  
Xiaoge Niu ◽  
Chong Shen ◽  
Fangchao Liu ◽  
Zhongying Liu ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Risk Score ◽  
Chinese Population ◽  
Cox Regression ◽  
Absolute Risk ◽  
Fasting Blood Glucose ◽  
Lifetime Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Increased Risk

Objective:To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.Methods:Using meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals.Results:During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age of 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (HR: 1.99, 95% CI: 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI: 22.5%-27.7%) and 13.6% (95% CI: 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed the lifetime risk as high as 41.1% (95% CI: 31.4%-49.5%). Moreover, individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of the low polygenic risk (from 34.6 % to 13.2%).Conclusions:Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH.Classification of Evidence:This study provides Class I evidence that a meta-polygenic risk score is predictive of stroke risk.

scholarly journals Association of social isolation, loneliness, and genetic risk with incidence of dementia: UK Biobank cohort study

2020 ◽  
Author(s):  
Marko Elovainio ◽  
Jari Lahti ◽  
Matti Pirinen ◽  
Laura Pulkki-Råback ◽  
Anni Malmberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Social Isolation ◽  
Genetic Risk ◽  
Significant Risk ◽  
Polygenic Risk Score ◽  
List Type ◽  
Uk Biobank ◽  
High Genetic Risk ◽  
Increased Risk ◽  
Socially Isolated

ObjectiveTo examine the associations of social isolation and loneliness with incident dementia by level of genetic risk.DesignProspective population-based cohort study.Setting and participants155 074 men and women (mean age 64.1, SD 2.9 years) from the UK Biobank Study, recruited between 2006 and 2010.Main exposuresSelf-reported social isolation and loneliness, and polygenic risk score for Alzheimer’s disease with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories.Main outcomeIncident all-cause dementia ascertained using electronic health records.ResultsOverall, 8.6% of participants reported that they were socially isolated and 5.5% were lonely. During a mean follow-up of 8.8 years (1.36 million person-years), 1444 (0.9% of the total sample) were diagnosed with dementia. Social isolation, but not loneliness, was associated with increased risk of dementia (hazard ratio 1.62, 95% confidence interval 1.38 to 1.90). Of the participants who were socially isolated and had high genetic risk, 4.2% (2.9% to 5.5%) were estimated to develop dementia compared with 3.1% (2.7% to 3.5%) in participants who were not socially isolated but had high genetic risk. The corresponding estimated incidence in the socially isolated and not isolated were 3.9% (3.1% to 4.6%) and 2.5% (2.2% to 2.6%) in participants with intermediate genetic risk.ConclusionSocially isolated individuals are at increased risk of dementia at all levels of genetic risk.What is already known on this topicSocial isolation and loneliness have been associated with increased risk of dementiaIt is not known whether this risk is modified or confounded by genetic risk of dementiaWhat this study addsThis is the first study to show that social isolation is associated with increased risk of dementia across the spectrum of genetic riskLoneliness, although considered as a significant risk for multiple health problems, seems to be associated with dementia only when combined with high genetic risk

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