scholarly journals Fitness, Physical Activity, and Cardiovascular Disease: Longitudinal and Genetic Analyses in the UK Biobank Study

2017 ◽  
Author(s):  
Emmi Tikkanen ◽  
Stefan Gustafsson ◽  
Erik Ingelsson
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Grip Strength ◽  
Cardiorespiratory Fitness ◽  
Genetic Risk ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
The Uk

AbstractBackgroundExercise is inversely related with cardiovascular disease (CVD), but large-scale studies of incident CVD events are lacking. Moreover, little is known about genetic determinants of fitness and physical activity, and modifiable effects of exercise in individuals with elevated genetic risk of CVD. Finally, causal analyses of exercise traits are limited.MethodsWe estimated associations of grip strength, physical activity, and cardiorespiratory fitness with CVD and all-cause death in up to 502,635 individuals from the UK Biobank. We also examined these associations in individuals with different genetic burden on coronary heart disease (CHD) and atrial fibrillation (AF). Finally, we performed genome-wide association study (GWAS) of grip strength and physical activity, as well as Mendelian randomization analysis to assess the causal role of grip strength in CHD.FindingsGrip strength, physical activity, and cardiorespiratory fitness showed strong inverse associations with incident cardiovascular events and all-cause death (for composite CVD; HR, 0.78, 95% CI, 0.77-0.80; HR, 0.94, 95% CI, 0.93-0.95, and HR, 0.67, 95% CI, 0.63-0.71, per SD change, respectively). We observed stronger associations of grip strength with CHD and AF for individuals in the lowest tertile of genetic risk (Pinteraction = 0.006, Pinteraction = 0.03, respectively), but the inverse associations were present in each category of genetic risk. We report 27 novel genetic loci associated with grip strength and 2 loci with physical activity, with the strongest associations in FTO (rs56094641, P=3.8×10-24) and SMIM2 (rs9316077, P=1.4×10-8), respectively. By use of Mendelian randomization, we provide evidence that grip strength is causally related to CHD.InterpretationMaintaining physical strength is likely to prevent future cardiovascular events, also in individuals with elevated genetic risk for CVD.FundingNational Institutes of Health (1 R01 HL135313-01), Knut and Alice Wallenberg Foundation (2013.0126), and the Finnish Cultural Foundation.

scholarly journals Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

scholarly journals Associations of discretionary screen time with mortality, cardiovascular disease and cancer are attenuated by strength, fitness and physical activity: findings from the UK Biobank study

BMC Medicine ◽  
2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Carlos A. Celis-Morales ◽  
Donald M. Lyall ◽  
Lewis Steell ◽  
Stuart R. Gray ◽  
Stamatina Iliodromiti ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Screen Time ◽  
Uk Biobank ◽  
The Uk

scholarly journals Using genetics to understand the causal influence of higher BMI on depression

2018 ◽  
Vol 48 (3) ◽  
pp. 834-848 ◽  
Author(s):  
Jessica Tyrrell ◽  
Anwar Mulugeta ◽  
Andrew R Wood ◽  
Ang Zhou ◽  
Robin N Beaumont ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Self Report ◽  
Uk Biobank ◽  
Men And Women ◽  
Statistical Confidence ◽  
The Uk ◽  
Genetically Determined

Abstract Background Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women. Methods We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to ‘uncouple’ the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and using subsets of BMI variants from known physiological pathways. Results Higher BMI was strongly associated with higher odds of depression, especially in women. Mendelian randomization provided evidence that higher BMI partly causes depression. Using a 73-variant BMI genetic risk score, a genetically determined one standard deviation (1 SD) higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.09, 1.28, P = 0.00007) and women only (OR: 1.24, 95% CI: 1.11, 1.39, P = 0.0001). Meta-analysis with 45 591 depression cases and 97 647 controls from the Psychiatric Genomics Consortium (PGC) strengthened the statistical confidence of the findings in all individuals. Similar effect size estimates were obtained using different Mendelian randomization methods, although not all reached P < 0.05. Using a metabolically favourable adiposity genetic risk score, and meta-analysing data from the UK biobank and PGC, a genetically determined 1 SD higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals (OR: 1.26, 95% CI: 1.06, 1.50], P = 0.010), but with weaker statistical confidence. Conclusions Higher BMI, with and without its adverse metabolic consequences, is likely to have a causal role in determining the likelihood of an individual developing depression.

scholarly journals Phenome-Wide Association Study of Actigraphy in the UK Biobank

2021 ◽  
Author(s):  
Thomas G. Brooks ◽  
Nicholas F. Lahens ◽  
Gregory R. Grant ◽  
Yvette I. Sheline ◽  
Garret A. FitzGerald ◽  
...  
Keyword(s):  
Physical Activity ◽  
Airway Obstruction ◽  
Large Scale ◽  
Diurnal Rhythms ◽  
Uk Biobank ◽  
Daily Lives ◽  
Individualized Approach ◽  
Using Data ◽  
The Uk ◽  
Chronic Airway

AbstractWrist-worn accelerometer actigraphy devices present the opportunity for large-scale data collection from people during their daily lives. Using data from approximately 100,000 participants in the UK Biobank, actigraphy-derived measures of physical activity, sleep, and diurnal rhythms were associated in exploration and validation cohorts with a full phenome-wide set of diagnoses, biomarkers and metadata. Rhythmicity was captured by two independent models based on accelerometer and skin temperature harnessing behavioral (diurnal) and molecular (circadian) components. We found that robust rhythms significantly with biomarkers, survival, and phenotypes including diabetes, hypertension, mood disorders, and chronic airway obstruction; these associations were comparable to those with physical activity and sleep. Surprisingly, associations were mostly consistent between the sexes, while modulation by age was significant. More importantly, rhythms were found to be powerful predictors of future diseases: a two standard deviation difference in wrist temperature rhythms corresponded to increases in rate of diagnosis of 61% in diabetes, 38% in chronic airway obstruction, 27% in anxiety disorders, and 22% in hypertension. Our PheWAS of actigraphy data in the UK Biobank establishes that rhythmicity is fundamental to modeling disease trajectories, as are physical activity and sleep. Integration of long-term remote biosensing into patient care could thus afford an individualized approach to risk management.

scholarly journals Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (1) ◽  
pp. e1003487
Author(s):  
Rema Ramakrishnan ◽  
Aiden Doherty ◽  
Karl Smith-Byrne ◽  
Kazem Rahimi ◽  
Derrick Bennett ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Lower Risk ◽  
Cox Regression ◽  
Moderate Intensity ◽  
Inverse Association ◽  
Uk Biobank ◽  
Reverse Causality ◽  
Vigorous Intensity ◽  
The Uk

Background Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD. Methods and findings We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013–2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose–response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies. Conclusions In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.

Abstract P879: Differences in Statistical Performance of Polygenic Risk Scores for Cardiovascular Disease Across Different Race/Ethnicities

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Julian N Acosta ◽  
Cameron Both ◽  
Natalia Szejko ◽  
Stacy Brown ◽  
Kevin N Sheth ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Logistic Regression ◽  
Genetic Risk ◽  
Regression Models ◽  
Risk Scores ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Logistic Regression Models ◽  
The Uk ◽  
Significant Health

Introduction: Genome-wide association studies have identified numerous genetic risk variants for stroke and myocardial infarction (MI) in Europeans. However, the limited applicability of these results to non-Europeans due to racial/ethnic differences in the genetic architecture of cardiovascular disease (CVD), coupled with the limited availability of genomic data in non-Europeans, may create significant health disparities now that genomic-based precision medicine is a reality. We tested the hypothesis that the performance of polygenic risk scores (PRS) for CVD differ in Europeans versus non-Europeans. Methods: We conducted a nested study within the UK Biobank, a prospective, population-based study that enrolled ~500,000 participants across the UK. For this study, we identified self-reported black participants and randomly matched them 1:1 by age and sex with white participants. We created a PRS using previously discovered loci for stroke and MI. We then tested whether this PRS representing the aggregate polygenic susceptibility to CVD yielded similar precision in black versus white participants in logistic regression models. Results: Of the 502,536 participants enrolled in the UK Biobank, 8,061 were self-reported blacks, with 7,644 having available data for our analyses. We randomly matched these participants with white individuals, leading to a total sample size of 15,288 (mean age 51.9 [SD 8.1], female 8,722 [57%]). The total number of events was 741 overall, with 363 happening in blacks and 378 happening in whites. In logistic regression models including age, sex, and 5 principal components, the statistical precision (e.g. narrower confidence intervals) for the PRS was substantially higher for whites (OR 1.22, 95%CI 1.08 - 1.37; p<0.0001) compared to blacks (OR 1.24, 95%CI 1.05-1.47; p=0.01). Secondary analyses using genetically-determined ancestry yielded similar results. Conclusion: Because CVD-related PRSs are derived mainly using genetic risk factors identified in populations of European ancestry, their statistical performance is lower in non-European populations. This asymmetry can lead to significant health disparities now that these tools are being evaluated in multiple precision medicine approaches.

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