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 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.

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.

Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach

2021 ◽  
pp. 109117
Author(s):  
Ellen W. Yeung ◽  
Kellyn M. Spychala ◽  
Alex P. Miller ◽  
Jacqueline M. Otto ◽  
Joseph D. Deak ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Risk Score ◽  
Genetic Risk ◽  
Polygenic Risk Score ◽  
Polygenic Risk

1134-P: Polygenic Risk Score of Type 2 Diabetes as a Predictive Factor for Macrovascular Complications: A Prospective Population-Based UK Biobank Study

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1134-P
Author(s):  
SANGHYUK JUNG ◽  
DOKYOON KIM ◽  
MANU SHIVAKUMAR ◽  
HONG-HEE WON ◽  
JAE-SEUNG YUN
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Predictive Factor ◽  
Population Based ◽  
Macrovascular Complications ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk

scholarly journals Unhealthy Lifestyle, Genetics and Risk of Cardiovascular Disease and Mortality in 76,958 Individuals from the UK Biobank Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4283
Author(s):  
Katherine M. Livingstone ◽  
Gavin Abbott ◽  
Joey Ward ◽  
Steven J. Bowe
Keyword(s):  
Cardiovascular Disease ◽  
Cohort Study ◽  
Polygenic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Uk Biobank ◽  
Unhealthy Lifestyle ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
The Uk ◽  
Cvd Mortality

To examine associations of unhealthy lifestyle and genetics with risk of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke. We used data on 76,958 adults from the UK Biobank prospective cohort study. Favourable lifestyle included no overweight/obesity, not smoking, physical activity, not sedentary, healthy diet and adequate sleep. A Polygenic Risk Score (PRS) was derived using 300 CVD-related single nucleotide polymorphisms. Cox proportional hazard ratios (HR) were used to model effects of lifestyle and PRS on risk of CVD and all-cause mortality, stroke and MI. New CVD (n = 364) and all-cause (n = 2408) deaths, and stroke (n = 748) and MI (n = 1140) events were observed during a 7.8 year mean follow-up. An unfavourable lifestyle (0–1 healthy behaviours) was associated with higher risk of all-cause mortality (HR: 2.06; 95% CI: 1.73, 2.45), CVD mortality (HR: 2.48; 95% CI: 1.64, 3.76), MI (HR: 2.12; 95% CI: 1.65, 2.72) and stroke (HR:1.74; 95% CI: 1.25, 2.43) compared to a favourable lifestyle (≥4 healthy behaviours). PRS was associated with MI (HR: 1.35; 95% CI: 1.27, 1.43). There was evidence of a lifestyle-genetics interaction for stroke (p = 0.017). Unfavourable lifestyle behaviours predicted higher risk of all-cause mortality, CVD mortality, MI and stroke, independent of genetic risk.

scholarly journals The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes

2020 ◽  
Vol 56 (6) ◽  
pp. 2001441 ◽  
Author(s):  
Tomoko Nakanishi ◽  
Vincenzo Forgetta ◽  
Tomohiro Handa ◽  
Toyohiro Hirai ◽  
Vincent Mooser ◽  
...  
Keyword(s):  
Risk Score ◽  
Disease Burden ◽  
Forced Expiratory Volume ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Alpha-1 antitrypsin deficiency (AATD), mainly due to the PI*ZZ genotype in SERPINA1, is one of the most common inherited diseases. Since it is associated with a high disease burden and partially prevented by smoking cessation, identification of PI*ZZ individuals through genotyping could improve health outcomes.We examined the frequency of the PI*ZZ genotype in individuals with and without diagnosed AATD from UK Biobank, and assessed the associations of the genotypes with clinical outcomes and mortality. A phenome-wide association study (PheWAS) was conducted to reveal disease associations with genotypes. A polygenic risk score (PRS) for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio was used to evaluate variable penetrance of PI*ZZ.Among 458 164 European-ancestry participants in UK Biobank, 140 had the PI*ZZ genotype and only nine (6.4%, 95% CI 3.4–11.7%) of them were diagnosed with AATD. Those with PI*ZZ had a substantially higher odds of COPD (OR 8.8, 95% CI 5.8–13.3), asthma (OR 2.0, 95% CI 1.4–3.0), bronchiectasis (OR 7.3, 95%CI 3.2–16.8), pneumonia (OR 2.7, 95% CI 1.5–4.9) and cirrhosis (OR 7.8, 95% CI 2.5–24.6) diagnoses and a higher hazard of mortality (2.4, 95% CI 1.2–4.6), compared to PI*MM (wildtype) (n=398 424). These associations were stronger among smokers. PheWAS demonstrated associations with increased odds of empyema, pneumothorax, cachexia, polycythaemia, aneurysm and pancreatitis. Polygenic risk score and PI*ZZ were independently associated with FEV1/FVC <0.7 (OR 1.4 per 1-sd change, 95% CI 1.4–1.5 and OR 4.5, 95% CI 3.0–6.9, respectively).The important underdiagnosis of AATD, whose outcomes are partially preventable through smoking cession, could be improved through genotype-guided diagnosis.

scholarly journals Diet-quality and its association with cardiovascular diseases and cancer incidence and all-cause mortality: a prospective cohort study from UK Biobank

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Fanny Petermann-Rocha ◽  
Stuart R. Gray ◽  
Jill Pell ◽  
Carlos Celis-Morales
Keyword(s):  
Cancer Incidence ◽  
Diet Quality ◽  
Lower Risk ◽  
Quality Score ◽  
Confounding Factors ◽  
Uk Biobank ◽  
Healthy Group ◽  
Oily Fish ◽  
All Cause Mortality ◽  
The Uk

AbstractIntroductionNewly available data from big scale studies conducted in the UK, such as the UK Biobank, offers the possibility to further explore the prospective association between a diet-quality score and health outcomes after accounting for the effect of important confounding factors. The aim of this work, therefore, was to investigate the association between a diet-quality score, with the incidence of cardiovascular diseases (CVDs), cancer and all-cause mortality.Material and methodsThis study includes 345,343 participants (age range: 39–73, 55.1% women) from the UK Biobank, a prospective population-based study. Using 21 standardised variables of diet (alcohol, bread, bread type, cereal, dried fruit, water, coffee, tea, cheese, oily fish, non-oily fish, salt added to food, spread type, fresh fruit, cooked vegetable, raw vegetables, milk type, poultry, beef, lamb, and pork) we created a diet-quality score (very healthy, healthy, unhealthy and very unhealthy) using principal-component factor analysis. Associations between the dietary-quality score (very unhealthy individuals were the reference group) and health outcomes (all-cause mortality, CVD and cancer incidence) were investigated using Cox-proportional hazard models. All analyses were performed using STATA 14 statistical software.ResultsIn comparison to individuals with a very unhealthy diet, those with a better diet-quality had a lower risk of all-cause mortality and cancer as well as incidence of CVD and cancer. For example, individuals classified in the very healthy group had a 12% lower risk of all-cause mortality (HR: 0.88 [95% CI: 0.82 to 0.95]), 12% lower risk of CVD incidence (HR: 0.88 [95% CI: 0.80 to 0.98]), 17% of all-cancer mortality (HR: 0.83 [95% CI: 0.75 to 0.93]), and 10% lower risk all-cancer incidence (HR: 0.90 [95% CI: 0.85 to 0.94]). Those in the healthy group had a 12% lower risk of all-cause (HR: 0.88 [95% CI: 0.83 to 0.93]) and 15% lower risk of all-cancer mortality (HR: 0.85 [95% CI: 0.78 to 0.93]). There was no significant association between CVD mortality and any diet-quality group. These findings were independent of major confounding factors including socio-demographic covariates, prevalent of diseases and lifestyle factors.DiscussionOur findings indicate that individuals with a healthy diet in the UK biobank cohort are associated with a lower risk of premature mortality, and incidence of CVDs and cancer independently of major confounding factors.

scholarly journals Self-reported hearing loss questions provide a good measure for genetic studies: a polygenic risk score analysis from UK Biobank

2020 ◽  
Vol 28 (8) ◽  
pp. 1056-1065
Author(s):  
Stacey S. Cherny ◽  
Gregory Livshits ◽  
Helena R. R. Wells ◽  
Maxim B. Freidin ◽  
Ida Malkin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Risk Score ◽  
Good Measure ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Genetic Studies ◽  
Polygenic Risk ◽  
Score Analysis

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.

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