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We proposed a statistical description of the locomotor activity tracks and transformed the provided time series into vectors representing physiological states for each participant.
The Principal Component Analysis of the transformed data revealed a winding trajectory with distinct segments corresponding to subsequent human development stages. We characterized the distance traveled along the aging trajectory as a natural measure of biological age and demonstrated its significant association with frailty and hazardous lifestyles, along with the remaining lifespan and healthspan of an individual.
The biological age explained most of the variance of the log-hazard ratio that was obtained by fitting directly to mortality and the incidence of chronic diseases. Our findings highlight the intimate relationship between the supervised and unsupervised signatures of the biological age and frailty, a consequence of the low intrinsic dimensionality of the aging dynamics.
The study designs used, however, are prone to confounding and are not able to establish the direction of causality. The current study overcomes these problems using the Mendelian randomisation design to determine the effect of alcohol consumption on the likelihood of reporting CWP. The UK Biobank recruited , participants aged between 40 and 69 years.
Data collected included questions on chronic pain and alcohol consumption, and biological samples providing genotypic information. Alcohol consumption was categorised as "weekly consumption" or "nonfrequent or infrequent. Associations between genotype, CWP, and alcohol consumption were tested by logistic regression.
Instrumental variable analysis was used to calculate the causal effect of weekly alcohol consumption on CWP. An interpretation of observational population studies as showing a protective effect of alcohol on CWP is not supported. Studies have shown that moderate alcohol consumption is strongly associated with reduced reporting of chronic widespread pain CWP.
In this study, we applied a multitrait GWAS approach to discover additional factor of the missing heritability of human anthropometric variation. Single-trait analysis identified SNPs with genome-wide significance threshold.
Multitrait meta-analysis of anthropometric variation validated 27 loci in a two-stage meta-analysis with a large British ancestry cohort, six of which are newly reported here p value threshold Conclusion Considering multiple-related genetic phenotypes improve associated genome signal detection.
These results indicate the potential value of data-driven multivariate phenotyping for genetic studies in large population-based cohorts to contribute to knowledge of complex traits. Background Heritability estimates have revealed an important contribution of SNP variants for most common traits; however, SNP analysis by single-trait genome-wide association studies GWAS has failed to uncover their impact.
Conclusion Considering multiple-related genetic phenotypes improve associated genome signal detection. If it were possible to unpick the association between personality and smoking, it may be possible to develop tailored smoking interventions that could lead to both improved uptake and efficacy.
Methods Recent genome-wide association studies GWAS have identified variants robustly associated with both smoking phenotypes and personality traits. Here we use publicly available GWAS summary statistics in addition to individual-level data from UK Biobank to investigate the link between smoking and personality. We first estimate genetic overlap between traits using LD score regression and then use bidirectional Mendelian randomisation methods to unpick the nature of this relationship.
Results We found clear evidence of a modest genetic correlation between smoking behaviours and both neuroticism and extraversion. We found some evidence that personality traits are causally linked to certain smoking phenotypes: among current smokers each additional neuroticism risk allele was associated with smoking an additional 0.
Background Despite the well-documented association between smoking and personality traits such as neuroticism and extraversion, little is known about the potential causal nature of these findings. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms.
METHODS: We examined the associations for adult height using logistic regression adjusted for potential confounders and genetically determined height using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables in , individuals of white ethnic background participating in the UK Biobank.
We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases.
Pathway analysis showed multiple height-associated pathways associating with individual diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis.
Multiple biological mechanisms affecting height may affect the risks of these diseases. Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear.
Sex stratification supported the causal role of higher BMI increasing bladder cancer mortality risk males but decreasing respiratory disease mortality risk males. Objective The aim of this study was to obtain estimates of the causal relationship between BMI and mortality. Design Prospective population based cohort study. 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 Results During a median follow-up of 7.
Objective To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke. Results During a median follow-up of 7. Large study populations with sufficient statistical power are required to detect the small effect sizes of the yet unidentified genetic variants.
However, the analysis of huge cohorts, like UK Biobank, is challenging. Here, we present an atlas of genetic associations for non-binary and binary traits of , UK Biobank participants of European ancestry. Genome-wide association studies GWAS have identified many loci contributing to variation in complex traits, yet the majority of loci that contribute to the heritability of complex traits remain elusive. The UK Biobank allows us to study the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.
Methods We analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes comparisons.
Results and conclusions Many of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV—phenotype associations were significant at a false discovery rate threshold of 0. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs.
Our work should inform clinicians in planning and managing the medical care of CNV carriers. Background Genomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits.
Conclusions: AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and alcohol use disorders. Alcohol use disorders are common conditions that have enormous social and economic consequences. Our objective was to examine the independent and combined association of maternal and own smoking with adult lung function and COPD. We calculated the additive interaction between maternal and own smoking on the outcomes of interest, and estimated the association with maternal smoking within categories of own smoking.
Results There was no strong evidence that maternal smoking influenced adult lung health among never smokers. The association between maternal smoking and COPD also varied by pack-years of own smoking, with a hazard ratio of 2. Limited evidence suggests that exposure to maternal smoking in utero or early life might be associated with chronic obstructive pulmonary disease COPD , but whether this is independent of later own smoking remains unclear.
However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes. Objectives This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.
Methods Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD metaGRS consisting of 1. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22, CAD cases and , noncases from the UK Biobank.
The corresponding HR was 2. Conclusions The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.
Background Coronary artery disease CAD has substantial heritability and a polygenic architecture. Using participants from the UK Biobank prospective cohort study, we evaluated whether the addition of a genetic risk score GRS could improve the performance of two previously validated models.
Inclusion of the GRS did not appreciably improve discrimination of either model, and led to substantial miscalibration. Following recalibration the discrimination did not change, but good calibration for models incorporating the GRS was recovered.
Colorectal cancer CRC risk prediction models could be used to risk-stratify the population to provide individually tailored screening provision. At present, provision of genetic information is not useful for risk stratification for CRC. Low statistical power and endogenous measures of environment have been obstacles to the credible estimation of such gene-by-environment interactions.
We overcome these obstacles by combining a natural experiment that generated variation in secondary education with polygenic scores for a quarter-million individuals. The additional schooling affected body size, lung function, and blood pressure in middle age. The improvements in body size and lung function were larger for individuals with high genetic predisposition to obesity.
As a result, education reduced the gap in unhealthy body size between those in the top and bottom terciles of genetic risk of obesity from 20 to 6 percentage points.
This work investigates whether genetic makeup moderates the effects of education on health. Here, we select 25 single nucleotide polymorphisms SNPs linked through genome-wide association studies GWAS to 19 candidate drug targets for common disease indications.
Phenome-wide association studies PheWAS have been proposed as a possible aid in drug development through elucidating mechanisms of action, identifying alternative indications, or predicting adverse drug events ADEs.
We describe associations that may predict ADEs, e. Our results demonstrate PheWAS as a powerful addition to the toolkit for drug discovery. Our study demonstrates that, as previously predicted, increasing GWAS sample sizes continues to deliver, by the discovery of new loci, increasing prediction accuracy and providing additional data to achieve deeper insight into complex trait biology. All summary statistics are made available for follow-up studies. We propose a two-degree-of-freedom test for jointly testing mean and variance effects to identify such variants.
We implement the test in a linear mixed model, for which we provide an efficient algorithm and software. To focus on biologically interesting settings, we develop a test for dispersion effects, that is, variance effects not driven solely by mean effects when the trait distribution is non-normal.
We identify and replicate novel associations with significant variance effects that cannot be explained by the non-normality of body mass index, and we provide suggestive evidence for a connection between leptin levels and body mass index variability. Identification of genetic variants with effects on trait variability can provide insights into the biological mechanisms that control variation and can identify potential interactions. The open resource is unique in its size and scope.
A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits.
Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million.
Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases. The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately , individuals from across the United Kingdom, aged between 40 and 69 at recruitment.
The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort UK Biobank who underwent keratometry and autorefraction at an assessment centre.
Genetic correlation between the two traits was calculated using LD Score regression. Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The genetic correlation between corneal and refractive astigmatism was 0. Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism.
The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism. To investigate this, we carried out genome-wide association studies of 3, functional and structural brain imaging phenotypes from UK Biobank discovery dataset 8, subjects.
Here we show that many of these phenotypes are heritable. The genetic architecture of brain structure and function is largely unknown.
Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and overall 17 genes involved in development, pathway signalling and plasticity.
Our results provide insights into the genetic architecture of the brain that are relevant to neurological and psychiatric disorders, brain development and ageing. The effect of ready-to-eat food environments that sell food for instant consumption on the risk of type 2 diabetes has received scant attention.
We therefore aimed to examine the association between exposure to ready-to-eat food environments and type 2 diabetes in a large and diverse population sample. Methods We conducted a cross-sectional study of adult male and female participants from the baseline phase of the UK Biobank cohort. Participants in this cohort were aged 37—73 years and resided in one of 21 cities in the UK.
Ready-to-eat food environments, which we determined from a modelled and linked built environment database, were objectively measured within 1-km catchment areas of the residential streets of participants and were expressed as metrics of density and proximity to the participants' homes. We used logistic regression models to examine the associations between exposure to ready-to-eat food environments and the odds of type 2 diabetes, adjusting for individual covariates such as physical activity.
As sensitivity analyses, we investigated the associations between the street distance to the nearest ready-to-eat food outlet and type 2 diabetes.
We also tested post hoc for effect modification by sex, income, body-mass index, and location of the UK Biobank collection centre. Top-down policies aimed at minimising unhealthy food access could potentially reduce unhealthy consumption and risks of chronic diseases. Further long-term studies are needed to effectively guide such interventions. Rapid urbanisation and associated socioeconomic transformations have modified current lifestyles, shifting dietary preferences towards ready-to-eat, calorie-dense food of poor nutritional quality.
Interpretation Access to ready-to-eat food environments was positively associated with type 2 diabetes. Whether this association extends to other health outcomes and whether it is independent of total amount of time walked are currently unknown. Therefore, the aim of this study was to investigate whether usual walking pace is associated with a range of health outcomes. Walking pace and total walking time were self-reported. The outcomes comprised: all-cause mortality as well as incidence and mortality from cardiovascular disease CVD , respiratory disease and cancer.
The associations were investigated using Cox proportional hazard models. Results Over a mean of 5. In a fully adjusted model, compared to slow pace walkers, men and women, respectively, with a brisk pace having lower risk of mortality from all-causes HR0. No associations were found for all-cause cancer, colorectal, breast cancer. However, brisk walking was associated with a higher risk of prostate cancer.
Conclusions Walking pace is associated with lower risk of a wide range of important health conditions, independently of overall time spent walking. Purpose Walking pace is associated with all-cause and cardiovascular disease CVD mortality. We evaluated 27 common SNPs in candidate genes previously reported to be associated with other sleep variables for association with self-reported habitual sleep duration in the UK Biobank in , individuals of European ancestry.
We also replicated a previously reported association in DRD2. Independent replication of these associations and a second signal in DRD2 rs was observed in an additional , participants of European ancestry from the UK Biobank. Short sleep duration has been linked to negative health effects, but is a complex phenotype with many contributing factors, including genetic.
We partitioned the heritability of both low-frequency 0. Common variant heritability has been widely reported to be concentrated in variants within cell-type-specific non-coding functional annotations, but little is known about low-frequency variant functional architectures.
Cell-type-specific non-coding annotations that were significantly enriched for h2c of corresponding traits were similarly enriched for h2lf for most traits, but more enriched for brain-related annotations and traits. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36, men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort.
We also undertook replication analyses in , men from the UK Biobank. The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rsT risk allele showed differential enhancer activity.
SIM1 is part of the leptin—melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function. Erectile dysfunction affects millions of men worldwide. Objective This prospective cohort study aimed to assess the association between physical activity and risk of oesophageal or gastric cancer.
Methods A cohort of , adults aged 40—69 years were identified from the UK Biobank, which recruited participants between and Physical activity and screen-based sedentary behaviour levels were not associated with overall oesophago-gastric cancer risk.
However, when compared with low levels, high physical activity levels were associated with a significantly reduced risk of gastric non-cardia cancer HR 0. Conclusion Moderate, rather than high, physical activity levels were associated with the strongest reductions in oesophageal adenocarcinoma risk in this large UK prospective cohort. Few observational studies have assessed the role of physical activity in oesophago-gastric cancer risk. The aim of the current study was to explore the associations of protein intake with bone mineral density BMD.
This indicates that higher protein intakes may be beneficial for both men and women. PURPOSE: Adequate dietary protein intake is important for the maintenance of bone health; however, data in this area is ambiguous with some suggestion that high protein intake can have deleterious effects on bone health. However, the impact, interplay, and underlying biological mechanisms among BMI, environment, genetics, and ancestry are not completely understood.
We observed substantial independent ancestry and nationality differences, including ancestry principal component interactions and nonlinear effects.
We then assessed the proportion of BMI variance explained by sex in the UKB using previously identified loci compared to previously and newly identified loci and found slight increases: from 3. Further, the variance explained by previously and newly identified variants decreased with increasing age in the GERA and UKB cohorts, echoed in the variance explained by the entire genome, which also showed gene—age interaction effects.
Finally, we conducted a tissue expression QTL enrichment analysis, which revealed that GWAS BMI-associated variants were enriched in the cerebellum, consistent with prior work in humans and mice. Previous studies have found common genetic factors that influence educational achievement, cognitive performance and total brain volume i. Here, in a large sample of participants from the UK Biobank, we investigate the shared genetic basis between educational attainment and fine-grained cerebral cortical morphological features, and associate this genetic variation with a related aspect of cognitive ability.
Importantly, we execute novel statistical methods that enable high-dimensional genetic correlation analysis, and compute high-resolution surface maps for the genetic correlations between educational attainment and vertex-wise morphological measurements.
We conduct secondary analyses, using the UK Biobank verbal—numerical reasoning score, to confirm that variation in educational attainment that is genetically correlated with cortical morphology is related to differences in cognitive performance. Our analyses relate the genetic overlap between cognitive ability and cortical thickness measurements to bilateral primary motor cortex as well as predominantly left superior temporal cortex and proximal regions.
These findings extend our understanding of the neurobiology that connects genetic variation to individual differences in educational attainment and cognitive performance. Individual differences in educational attainment are linked to differences in intelligence, and predict important social, economic, and health outcomes.
We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity, but a favourable metabolic profile. These individuals also had higher subcutaneous fat, but lower liver fat and lower visceral-to-subcutaneous adipose tissue ratio.
Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. Avery and Laurent Tellier and Ana I.
Vazquez and Gustavo de los Campos and Stephen D. The proportion of variance explained for height is comparable to the estimated common SNP heritability from genome-wide complex trait analysis GCTA , and seems to be close to its asymptotic value i. Thus, our results close the gap between prediction R-squared and common SNP heritability. Our primary dataset is the UK Biobank cohort, comprised of almost k individual genotypes with multiple phenotypes.
We construct genomic predictors for heritable but extremely complex human quantitative traits height, heel bone density, and educational attainment using modern methods in high dimensional statistics i.
A better understanding of the genetic background of CAD in this population has the potential to suggest novel molecular targets for screening, risk assessment and drug development. Our results were compared with results from participants without diabetes.
Moreover, other variants previously associated with CAD showed similar effects in the participants with and without diabetes, indicating that the genetic architecture of CAD is largely the same.
Larger studies are needed to establish whether there are important diabetes-specific CAD loci. The effect of feedback was found to be strongly moderated by household income, with those in higher income households accounting for seemingly all of the estimated effect due, in part, to increased physical activity.
They do however also highlight that the differential response to the provision of health information may be a driver of health inequalities and that the provision of feedback may bias longitudinal health studies. Each cohort conducted genotyping using commercially available arrays followed by imputation.
GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure.
Back pain is the 1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. The discovery sample comprised , individuals, including 29, CBP cases. GlnTer rs risk allele in the myocilin gene MYOC was initially reported to have high penetrance in glaucoma registry-based studies, but much lower estimates were recently obtained from population-based studies.
We investigated this disparity using data from Australia and the United Kingdom. GlnTer variant with glaucoma and ocular hypertension OHT. Carriers of the MYOC p. GlnTer variant were identified using genotype imputation from arrays. In contrast, 2 Australian registry-based studies, the Australian and New Zealand Registry of Advanced Glaucoma and the Glaucoma Inheritance Study in Tasmania, ascertained glaucoma cases referred by eye care clinicians, with historic control participants recruited from other Australian studies.
Samples were either directly sequenced or had genotypes determined by imputation for the Australian registry and historic control participants. GlnTer variants in participants with glaucoma and OHT. GlnTer variant was 1 in individuals 0. The odds ratio of p. The penetrance of the MYOC p. GlnTer variant was 7. GlnTer variant were GlnTer variant confers a very high-risk effect size for advanced glaucoma; the risk is lower in nonadvanced glaucoma and OHT.
GlnTer carriers 65 years and older had glaucoma or OHT, with higher prevalence in the Australian registry studies.
Importance The p. Design Two sample, bidirectional mendelian randomisation study. Setting Genetic data taken from various cohorts comprised of the general population mostly individuals of European ancestry, plus a small proportion of other ancestries ; follow-up analysis included individuals from the United Kingdom.
Main outcome measures Subjective wellbeing and 11 measures of cardiometabolic health coronary artery disease; myocardial infarction; total, high density lipoprotein, and low density lipoprotein cholesterol; diastolic and systolic blood pressure; body fat; waist to hip ratio; waist circumference; and body mass index. Objectives To investigate whether the association between subjective wellbeing subjective happiness and life satisfaction and cardiometabolic health is causal. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation.
Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. Predictors were further studied with univariable and multivariable Cox regression analyses incident events. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. Results: Machine learning confirmed several known age, sex, obesity, pregnancy, history of deep vein thrombosis and identified several new risk factors for varicose vein disease, including height.
After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins hazard ratio for upper versus lower quartile, 1. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
Varicose veins are a common problem with no approved medical therapies. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins inverse-variance weighted: odds ratio, 1. Conclusions: Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins.
Unlike other biomarkers, germline genetic markers do not change with disease progression or treatment. In this paper, we test whether a germline genetic approach informed by physiology can be used to deconstruct T2D heterogeneity. First, we aimed to categorize genetic loci into groups representing likely disease mechanistic pathways. Second, we asked whether the novel clusters of genetic loci we identified have any broad clinical consequence, as assessed in four separate subsets of individuals with T2D.
We identified five robust clusters of T2D loci and traits, each with distinct tissue-specific enhancer enrichment based on analysis of epigenomic data from 28 cell types. Two clusters contained variant-trait associations indicative of reduced beta cell function, differing from each other by high versus low proinsulin levels.
The three other clusters displayed features of insulin resistance: obesity mediated high body mass index [BMI] and waist circumference [WC] , "lipodystrophy-like" fat distribution low BMI, adiponectin, and high-density lipoprotein [HDL] cholesterol, and high triglycerides , and disrupted liver lipid metabolism low triglycerides. Increased cluster genetic risk scores were associated with distinct clinical outcomes, including increased blood pressure, coronary artery disease CAD , and stroke.
Limitations of this study include that the genetic variants used in the cluster analysis were restricted to those associated with T2D in populations of European ancestry. Classification of patients by these genetic pathways may offer a step toward genetically informed T2D patient management. Additionally, we investigated the molecular differences between hypothyroidism and hyperthyroidism using genome-wide data. LMS IDEAL has been designed to use image acquisition protocols that can be installed on most MRI scanners and cloud-based image processing to provide fast, standardized clinical results.
The study explores whether driving is also associated with other unhealthy lifestyle factors. The associations were explored using chi-square tests for trend and binary logistic regression.
Results Of the participants who drove, It may have additional impact mediated through its effect on other aspects of lifestyle. Driving is a common type of sedentary behaviour; an independent risk factor for poor health. Conclusions Sedentary behaviour, such as driving, is known to have an independent association with adverse health outcomes. People with long driving times are at higher risk and might benefit from targeted interventions. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, is most informative for predicting risk of obesity sequellae, including cardiometabolic disease and cancer.
We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio adjusted for BMI WHRadjBMI , and identified signals in loci.
Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease. One in four adults worldwide are either overweight or obese.
But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant.
To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.
Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype.
CMR enables accurate quantification of the cardiac chamber volume, ejection fraction and myocardial mass, providing information for diagnosis and monitoring of CVDs. However, for years, clinicians have been relying on manual approaches for CMR image analysis, which is time consuming and prone to subjective errors.
It is a major clinical challenge to automatically derive quantitative and clinically relevant information from CMR images. The network is trained and evaluated on a large-scale dataset from the UK Biobank, consisting of 4, subjects with 93, pixelwise annotated images. On a short-axis image test set of subjects, it achieves an average Dice metric of 0. The mean absolute difference between automated measurement and manual measurement is 6.
On long-axis image test sets, the average Dice metric is 0. The performance is comparable to human inter-observer variability. We aimed to determine the shorter and longer term associations between RDW and incident common conditions in participants free of baseline disease, followed for 9 years. Participants were free of anemia, CAD, type-2 diabetes, stroke, hypertension, COPD, and any cancer except non-melanoma skin cancer at baseline. Survival models with competing Hazards tested associations with outcomes from hospital admission records and death certificates.
Higher Red Blood Cell Distribution Width RDW or anisocytosis predicts incident coronary artery disease CAD plus all-cause and cardiovascular mortality, but its predictive value for other common diseases in healthy volunteers is less clear. However, whether pathways leading to albuminuria are causal for cardiometabolic diseases is unclear.
We addressed this question using a Mendelian randomization framework in the UK Biobank, a large population-based cohort. We first performed a genome-wide association study for albuminuria in , individuals and identified 32 new albuminuria loci. We constructed albuminuria genetic risk scores and tested for association with cardiometabolic diseases. Genetically elevated albuminuria was strongly associated with increased risk of hypertension 1. Excretion of albumin in urine, or albuminuria, is associated with the development of multiple cardiovascular and metabolic diseases.
We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women 16, cases and , controls , uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors rs in TP53, rs in TERT, rs and rs in ATM, and rs at OBFC1 and four signals are located at established risk loci for hormone-related traits endometriosis and breast cancer at 1q Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population.
Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.
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Bennett for a collection of heels perfect for the fashion-forward bride. The high- and fine-jewelry collection, entitled Paper Moon, includes petal-inspired pendants, ear r ings, bracelets and rings in highly polished platinum, adorned with tanzanite or Tiffany yellow diamonds. Oliver Cabell CEO Scott Gabrielson previously worked with British designer Cole Buxton for a limited-edition shoe that sold out in less than two minutes and had a person wait list.
Should you not make it to the top of the queue for this collaboration, Oliver Cabell regularly drops other low top sneakers and super soft Chelsea boots in limitedquantities. Featuring vegetable-tanned leathers, the line is designed in New York and crafted in Italy. Now, Jang is introducing his first ready-to-wear collection featur ing t-shir ts, sweaters, jackets, and other outer wear, all designed and made in New York City.
A highlight of the collection: The buttery soft Owen suede jacket, perfect for early summer nights. Elegant or playful, these summer accessories for day or night are sure to make a splash this summer. From Nantucket to St. Tropez, nautical stripes and sea-inspired accessories are a classic summer must-have. The newest collaboration, announced in Los Angeles at a large-scale celebration, is with the highly renowned Shepard Fairey whose works are in the collections of such prestigious museums as Los Angeles County Museum of Art and the Museum of Modern Art in New York.
Fairey is not only a contemporary street artist, but also a graphic designer, illustrator and activist. The concept for the watch was inspired by the classic Meccano mechanical construction toys, and the watch movement has a geardriven mechanical aesthetic. The bold architectural design of the skeletonized manually-wound movement, with a 10day cogwheel power reserve indicator, is comprised of components. The HUB movement is designed to offer 10 days of power reserve, hence the name Meca For the Big Bang Meca Shepard Fairy series there are two timepieces being offered, one in gray with bold red accents, and one in blue.
Each version boasts several features designed by Fairey. Could customized shampoos, conditioners and other hair-care treatments spell the end of bad hair days forever? I felt like I was ordering a salad when, in fact, I was picking out my shampoo from Prose, a new customized hair-care line that lets devotees build natural, eco-certified products from scratch. In five days, I would receive my kit, complete with a gentle cleansing shampoo no silicone, please , a color-protective conditioner hold the heavy oils and a volumizing mask, all tailored to my exact hair type and climate conditions, infused with my preferred violet scent and stamped with my name on the bottles.
Welcome to the world of personalized hair-care, a rapidly expanding market filled with smart-tech brands that want to radically transform the traditional one-size-fits-all approach. In the era of customized everything sneakers, vitamins, lipstick , one could argue that hair-care has lagged sorely behind. Whether in the drugstore or at the salon, the range of formulas only speaks to pre-determined hair types and needs, the ingredients may contain outdated chemicals or animal by-products, and the search for a suitable match usually involves a lot of time, trial-and-error and half-empty bottles in your bathroom.
And frankly, women—and men—are over it. That team devised a proprietary algorithm that delves into strand structure, scalp moisture and 17 different hair goals from fixing split ends to de-. Getting this personal allows brands to directly zero in on those whose hair needs have been largely ignored or underserved until now. Form, for example, speaks to women from all different ethnic backgrounds who have a variety of textures.
After probing this data, Form gives you a cu-. More inclusive hair-care means rarely talked-about issues— like hair loss—are now part of the customization conversation. Danish clinic Harklinikken, for instance, now offers online assessments to diagnose hair loss and thinning an issue that affects 45 percent of women and men in the U.
Beyond the convenience factor, the results are impressive. German dermatologist Timm Golueke, M. For some, though, thinking about your mane on such a micro level can be overwhelming. In that case, having an expert weigh in can be hugely helpful. Prose, for example, partners with salon stylists who can guide you through their online assessment, and Beauty of Function opened a lab in New York City this spring where you can work out your formula with a pro and see it made on the spot.
In true Jetsons-style, a Customizer machine takes all that data and mixes up personalized products, dispensed in bottles while you wait. With zero guesswork involved, consider this the wave of the future. A look at other beauty goods that let you get up close and personalized.
Fragrance: Hawthorne taps into your body chemistry and lifestyle habits to identify your ideal scent preferences, which it translates into bespoke colognes. Skincare: LOLI Beauty lets you blend your own formulas in minutes: just take the powdered base and spike it with nutrientrich mix-ins, like hydrating prickly pear seed extract or firming red maca root, to form everything from cleansers to scrubs to face oils, suited to your needs.
Perfumery for men is evolving, just as fashion is. Belletrud, who also created such iconic scents as Jean Paul Gaultier Classique and Opium Pour Homme by Yves Saint Laurent, began studying fragrance under the tutelage of his father, a perfumer, at age 8.
For me, this is the definition of luxury. Remember, your microbiome that six pounds of bacteria living in your gut is dictating almost everything about your health—from your mood, ability to lose or gain weight, energy levels, sex drive and skin clarity.
These beauty-boosting superfoods pay-it-forward to girls in need. Each meal replacement Kalumi bar is fortified with beautyboosting super foods including marine collagen peptides, vitamin-rich sweet potatoes and organic yacon syrup. These nutritious ingestibles are designed to keep you fit, full and gorgeous. The dynamic duo behind Sakara Life launch a day customizable cleanse that begins in your own kitchen. The entrepreneur saw the superfood being used by women in East Africa to heal wounds, soothe scars and as a plant-based medicine for various ailments.
I finish off with a Lepaar Skin lip balm on my lips and a touch on the highs of my cheekbones. A f ter a lot of brainstorming and sourcing, we decided that pearls were our key ingredient.
Our skincare and makeup products are all about making your skin radiant and luminous, as well as looking healthy and natural. The main ingredient, pearls, reportedly offer light reflecting properties that instantly even the appearance of your complexion, heal imperfections, reduce redness, and assist regenerating anti-aging collagen.
Pearls are also rich in amino acids and minerals for intense hydration. The line, which includes both skincare as well as cosmetics, contains no parabens or sulfates and does not test on animals. Hart herself uses much of the line in her own beauty regimen. I also like to use vitamin mists and sprays to help keep my skin supple and radiant throughout the day. Why sit in hours of traffic when you can start enjoying your weekend NOW?
FOXTROT is the first aviation experience brand to operate its own fleet allowing us to control your entire flight from the website booking to the helipad and everything in between. We never use outside vendors, so the experience you have in New York is the same experience you will have in Miami and Los Angeles. Let our experienced pilots and team of professionals expedite your weekend.
Pat Day and his team leverage over 88 years of combined experience to deliver best-in-class flights every time. A luxurious, stress-free ride above the crowds or sit on a congested highway? You decide. In a townhouse in SoHo, Arthur Becker lives the loft life surrounded by the things he loves. Becker and Dankner met at a showhouse event in the Hamptons, and they agreed to meet again in Manhattan to discuss using the new townhouse.
I love sitting in the parlor surrounded by the things I love. Antiquities have a deep resonance. Although he took a long and successful detour into the business world, he majored in ceramics and photography in college. His artwork Money Mandalas and Moneyflies merge both of those worlds. The Mandalas series is inspired by the geometric shapes of Tibetan thangkas, and Money Flies questions our perceptions of value, vanity and ego.
He is currently at work on a large-scale installation for the St. James Building in Boston. Having already installed Money Mandala and Money Flies in the space, he is expanding that project with a set of dining tables and chairs that are created from coins and primitive objects. The chair backs are scaled-up Qin Dynasty coins shaped like a truncated man with f lared pants.
The seats will be made of plexiglass, so that they disappear, and it will just look like a row of coins. With the use of technology I am trying to make them part of modern life. Cash Crush, , by Arthur Becker, is made from digital printed currency and money bands. Over the fireplace, Money Flies by Becker. The dining room table by Restoration Hardware is illuminated by a chandelier by Reagan Hayes. Arthur Becker at home. This theory was solidified in New York City this past winter; Whispering Angel was nowhere to be found on store shelves—it was so popular during summer, the island of Manhattan nearly ran out of it.
Uncover the beauty of your home with a stylish Clopay garage door. With so many distinctive choices, you can rejuvenate your home with a dramatic entrance that makes a bold statement. Imagine what you can do with Clopay!
Owned and made in the U. Father-and-son team Juan Manuel and Lino Vicente Fayen were faced with the same predicament, and in response, they developed Collec tion Suites, an exclusive complex opening this summer where car aficionados can create a personal retreat among their prized passions.
Each unit—there are 38 in total, ranging from 2, to 2, square feet in size—features upscale amenities such as Italian tiles, Swiss wood floors, wet bar with wine fridge, Sonos entertainment system, bathroom with luxury finishes, integrated security system and automated LED lights.
Owners can also store wine, art and other collectibles. More importantly, Collection Suites offers complete anonymity. But for high-net-worth collectors, price seldom plays a main role in decision-making. Juan Manuel with a replica of the Shelby Cobra, made by Kirkham, that Carol Shelby himself says might be even better than the original. Spring will bring a new name to the fold—textile artist Kelly Hoppen. I wanted to make sure that my designs complimented the existing collections perfectly and would encompass both a masculine and feminine feel.
Since launching in , One Kings Lane has proven itself to be a design mecca for shoppers. Though the 3,square-foot Southampton store opened originally as a seasonal pop-up shop, ahead of its two-year anniversary it has become a successful brick-and-morter addition to the local scene.
This summer there is a full slate of special appearances and in-store events planned. To set themselves apart from the rest of the East End home boutiques, One Kings Lane also features an eclectic selection of one-ofa-kind vintage pieces ranging from furniture to accessories. For inspiration, check out the colorful surfboards hanging on the walls or the ornate bubble and rope artwork adorning the ceiling. As the brand continues to grow, they are gearing up for the fall opening of their New York City flagship store in SoHo.
Housed in a yearold Federal-style building that was originally built as a residence, it now boasts a glass addition and 3,square-feet of retail space. Two years after a devastating cyclone, Fiji has rebounded as a culturally immersive destination, particularly for jetsetters attracted to both luxury and ecotourism.
I checked my inbox and found an urgent email asking to reschedule my call with Andrew Griffiths, owner of the new Six Senses Fiji: Tropical Cyclone Keni, a category 3 storm with projected mile-per-hour winds, was due to make landfall on Fiji in less than 24 hours. As I sat safely at home some 8, miles away, I frantically checked the news, worried that history was about to repeat itself. As unpredictable natural disasters become more commonplace consider the U.
In the last two years, there have been a bevy of new resort developments and increased flight service including a direct route on Fijian Airways from San Francisco to Nadi International Airport. And travelers have taken note: Last year, Fiji saw more than double the annual visitors of similarly castaway-chic destinations, like French Polynesia and the Seychelles, plus a 17 percent increase in U.
At Nanuku Auberge Resort, for example, one of the hallmark experiences is the. Endeliquid utesequ iature es acerrum nulparinetur sequaes torerferum idellia eprovid quis quam quid eaque posant mollupt assunt, nestrum quia audi conectam con eriorat as prectec tatur, quas sum qui dolore volorerum dolore offic te as inus sdf apeliquo beatin con re conse omnihilique sdf cus maxim quod que repu dip idigenit velignmus, et dolores doloreris mos.
At Kokomo Private Island—on the southern fringes of the archipelago, in the Kadavu island group—guests have access to plus dive sites on the Great Astrolabe Reef. This scuba-diving pinnacle is filled with kaleidoscopic soft corals, underwater caverns and all kinds of aquatic life—from manta rays to green turtles and spinner dolphins.
This sustainable ethos has become central to the guest experience: You can tour the organic gardens, participate in beach clean-up and even assist with coral planting just off the shore a marine biologist was enlisted to introduce coral gardens years before the resort even opened.
This remote paradise is inextricably linked to foreign visitors, but its emphasis on the local culture and the environment are essential. The Hilltop Estate Villa is just one of the 25 villas available at Laucala.
At least it used to be; enter, the chopper. Rush-hour traff ic, which prevents you from arriving at your summer house until half the weekend is gone, is suddenly no longer a cause of anxiety as you blade over the traffic quells and land in mere minutes at your destination, sans road rage. Patrick Day, CEO of private air charter company Foxtrot, says helicopter travel has evolved the way that people vacation these days, allowing customers to seamlessly arrive at their destination without waiting in crowded airport lines, or dealing with rush hour traffic.
They make sure the entire experience is safe, and headache-free. Passport to Well-Being Health-minded jetsetters are finding more and more high-end resorts creating unparalleled packages that offer rejuvenation and transformation.
Wellness is the new wealthy and discerning jetsetters are looking for higher level spa services—and are willing to spend to get exclusive access. That has bred a new trend-within-a-trend where luxury hotels are offering elevated and exclusive wellness experiences only available at their properties.
Some destinations are setting a higher bar by welcoming just a limited number of guests at any one time. For example, the Golden Door in Escondido, California only allows 40 guests per week to attend, The Ranch Malibu hosts just 18 guests at a time for their wellness retreats, and COMO Shambhala in Bali has under 50 rooms available, all of which are privately perched in the jungle. Another method of appealing to clients is by offering access to big names in the wellness industry who host retreats, create classes, or develop spa treatments, allowing visitors to become immersed in their teachings.
All unique sessions provide a one-of-a-kind experience that creates a sense of balance and understanding. The Mandrake Hotel in London enlisted celeb-favorite practitioner Louka Leppard to create a Tulayoga program for the property that combines massage, inverted yoga, meditation and the use of breath to release withheld emotion, physical tension, and stress.
But more than just having big names in the wellness industry attached to big names in the luxury hospitality industr y, high-end properties across the globe are going out of their way to be the star attraction for people who travel to cater to their wellness fantasies.
Inkaterra Hacienda Urubamba, a contemporary hotel located in the heart of Urubamba Valley, offers many authentic Andean. For example, guests can partake in the Payment to the Earth ceremony—an ancient ritual for giving thanks to the Andean gods, performed by a local shaman—and a unique Pachamanca dining experience when a traditional Peruvian dish is cooked underneath the ground.
Rosewood Mayakoba just introduced the Marry Oneself Journey. The four-day personal retreat focuses on self-love, was inspired by ancient Mayan traditions, and is designed to re-connect guests with their inner selves. And Taj Hotels offers locally-inspired services at their signature Jiva Spas, like the saffron-infused bath at Taj Usha Kiran Palace, which is accompanied by live classical music akin to ancient royal traditions undertaken before an important coronation or wedding ceremony.
Even Las Vegas, the City of Sin, is jumping on the wellness wagon. Fit for a McQueen A new documentary gives a revealing insight into the avant garde designer through exclusive interviews and a deep dive into his runway collections.
Now, his rags-to-riches ascent to fashion royalty will be canonized in three upcoming films, including McQueen, a documentary arriving in theaters July After leaving high school, he found refuge in making clothes.
What followed is fashion history. McQueen, both at his own house and eventually as creative director at Givenchy, repeatedly set the industry ablaze—sometimes literally. W hen Gra nd ma Ellen, not the milk-and-cookies type, pa sses away, it unlea shes a n ev il, seemingly genetically linked, force upon mom Annie Toni Collette , dad Steve Gabriel Byrne and their two kids, Peter and Charlie.
Jonathan Safran Foer continues his crusade against factory farming with a new documentary produced by Natalie Portman. These facts now form the basis of the timely-asever documentary version of Eating Animals, coproduced by Foer w ith Oscar-w inning actress and longtime friend Natalie Portman, whom he credits with conceiving the adaptation early on.