Genome-wide association studies in economics and entrepreneurship research: promises and limitations

The recently developed genome-wide association study (GWAS) design enables the identification of genes specifically associated with economic outcomes such as occupational and other choices. This is a promising new approach for economics research which we aim to apply to the choice for entrepreneurship. However, due to multiple testing issues, very large sample sizes are needed to differentiate between true and false positives. For a GWAS on entrepreneurship, we expect that a sample size of at least 30,000 observations is required

Serum uric acid and chronic kidney disease: The role of hypertension

Background: There are inconsistent findings on the role of hyperuricemia as an independent risk factor for chronic kidney disease (CKD). Hypertension has been implicated as a factor influencing the association between serum uric acid and CKD. In this population-based study we investigated the association between serum uric acid and decline in renal function and tested whether hypertension moderates this association. Methods: We included 2601 subjects aged 55 years and over from the Rotterdam Study. Serum uric acid and estimated glomerular filtration rate (eGFR) were assessed at baseline. After average 6.5 years of follow-up, second eGFR was assessed. CKD was defined as eGFR<60 ml/min/1.73 m2. All associations were corrected for socio-demographic and cardiovascular factors. Results: Each unit (mg/dL) increase in serum uric acid was associated with 0.19 ml/min per 1.73 m2 faster annual decline in eGFR. While the association between serum uric acid and incidence of CKD was not significant in our study population (Hazard Ratio: 1.12, 95% confidence interval [CI]: 0.98-1.28), incorporating our results in a meta-analysis with eleven published studies revealed a significant association (Relative Risk: 1.18, 95%CI: 1.15-1.22). In the stratified analyses, we observed that the associations of serum uric acid with eGFR decline and incident CKD were stronger in hypertensive subjects (P for interaction = 0.046 and 0.024, respectively). Conclusions: Our findings suggest that hyperuricemia is independently associated with a decline in renal function. Stronger association in hypertensive individuals may indicate that hypertension mediates the association between serum uric acid and CKD

Alcohol consumption and risk of peripheral arterial disease: the Rotterdam study

Moderate alcohol consumption is associated with a reduced risk of cardiovascular disease. Data on alcohol consumption and atherosclerosis are scarce. To determine the association between alcohol consumption and risk of peripheral arterial disease, the authors carried out a cross-sectional study (1990-1993) in the population-based Rotterdam Study among men and women aged 55 years or over. Data on alcohol consumption and peripheral arterial disease, as measured by the ankle/brachial blood pressure index, were available for 3,975 participants without symptomatic cardiovascular disease. Male

Physical activity types and atrial fibrillation risk in the middle-aged and elderly: The Rotterdam Study

Background: The association between physical activity and atrial fibrillation remains controversial. Physical activity has been associated with a higher and lower atrial fibrillation risk. These inconsistent results might be related to the type of physical activity. We aimed to investigate the association of total and types of physical activity, including walking, cycling, domestic work, gardening and sports, with atrial fibrillation. Design: Prospective cohort study. Methods: Our study was performed in the Rotterdam Study, a prospective population-based cohort. We included 7018 participants aged 55 years and older with information on physical activity between 1997–2001. Cox proportional hazards models were used to examine the association of physical activity with atrial fibrillation risk. Models were adjusted for biological and behavioural risk factors and the remaining physical activity types. Physical activity was categorised in te

Reduced penetrance of pathogenic ACMG variants in a deeply phenotyped cohort study and evaluation of ClinVar classification over time

Purpose: We studied the penetrance of pathogenically classified variants in an elderly Dutch population from the Rotterdam Study, for which deep phenotyping is available. We screened the 59 actionable genes for which reporting of known pathogenic variants was recommended by the American College of Medical Genetics and Genomics (ACMG), and demonstrate that determining what constitutes a known pathogenic variant can be quite challenging. Methods: We defined “known pathogenic” as classified pathogenic by both ClinVar and the Human Gene Mutation Database (HGMD). In 2628 individuals, we performed exome sequencing and identified known pathogenic variants. We investigated the clinical records of carriers and evaluated clinical events during 25 years of follow-up for evidence of variant pathogenicity. Results: Of 3815 variants detected in the 59 ACMG genes, 17 variants were considered known pathogenic. For 14/17 variants the ClinVar classification had changed over time. Of 24 confirmed carriers of these variants, we observed at least one clinical event possibly caused by the variant in only three participants (13%). Conclusion: We show that the definition of “known pathogenic” is often uncle

De genetica van ondernemerschap

genetiGenoombreed associatieonderzoek is een moderne onderzoeksmethode die het mogelijk maakt genen te vinden die geassocieerd zijn met allerlei ziekten en menselijke eigenschappen. Een samenwerkingsverband tussen de Erasmus School of Economics en het Erasmus Medisch Centrum probeert deze veelbelovende methode toe te passen op de keuze voor ondernemerschap

Physical activity derived from questionnaires and wrist-worn accelerometers

_Background:_ Agreement between questionnaires and accelerometers to measure physical activity (PA) differs between studies and might be related to demographic, lifestyle, and health characteristics, including disability and depressive symptoms. _Methods:_ We included 1,410 individuals aged 51–94 years from the population-based Rotterdam Study. Participants completed the LASA Physical Activity Questionnaire and wore a wrist-worn accelerometer on the nondominant wrist for 1 week thereafter. We compared the Spearman correlation and disagreement (level and direction) for total PA across levels of demographic, lifestyle, and health variables. The level of disagreement was defined as the absolute difference between questionnaire- and accelerometer-derived PA, whereas the direction of disagreement was defined as

Methods of data collection and definitions of cardiac outcomes in the Rotterdam Study

The prevalence of cardiovascular diseases is rising. Therefore, adequate risk prediction and identification of its determinants is increasingly important. The Rotterdam Study is a prospective population-based cohort study ongoing since 1990 in the city of Rotterdam, The Netherlands. One of the main targets of the Rotterdam Study is to identify the determinants and prognosis of cardiovascular diseases. Case finding in epidemiological studies is strongly depending on various sources of followup and clear outcome definitions. The sources used for collection of data in the Rotterdam Study are diverse and the definitions of outcomes in the Rotterdam Study have changed due to the introduction of novel diagnostics and therapeutic interventions. This article gives the methods for data collection and the up-to-date definitions of the cardiac outcomes based on international guidelines, including the recently adopted cardiovascular disease mortality definitions. In all, detailed description of cardiac outcome definitions enhances the possibility to make comparisons with other studies in the field of cardiovascular research and may increase the strength of collaborations

Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies

Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called ‘missing heritability’. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51–62% in the number of genome-wide significant loci and a relative loss in polygenic score R2of 36–38%). Hence, cross-study heterogeneity contributes to the missing heritability

Associations of Activity and Sleep With Quality of Life: A Compositional Data Analysis

Introduction: Associations between time spent on physical activity, sedentary behavior, and sleep and quality of life are usually studied without considering that their combined time is fixed. This study investigates the reallocation of time spent on physical activity, sedentary behavior, and sleep during the 24-hour day and their associations with quality of life. Methods: Data from the 2011–2016 Rotterdam Study were used to perform this cross-sectional analysis among 1,934 participants aged 51–94 years. Time spent in activity levels (sedentary, light-intensity physical activity, moderate-to-vigorous physical activity, and sleep) were objectively measured with a wrist-worn accelerometer combined with a sleep diary. Quality of life was measured using the EuroQoL 5D-3L questionnaire. The compositional isotemporal substitution method was used in 2018 to examine the association between the distribution of time spent in different activity behaviors and quality of life. Results: Reallocation of 30 minutes from sedentary behavior, light-intensity physical activity, or sleep to moderate-to-vigorous physical activity was associated with a higher quality of life, whereas reallocation from moderate-to-vigorous physical activity to sedentary behavior, light-intensity physical activity, or sleep was associated with lower quality of life. To illustrate this, a reallocation of 30 minutes from sedentary behavior to moderate-to-vigorous physical activity was associated with a 3% (95% CI=2, 4) higher quality of life score. By contrast, a reallocation of 30 minutes from moderate-to-vigorous physical activity to sedentary behavior was associated with a 4% (95% CI=2, 6) lower quality of life score. Conclusions: Moderate-to-vigorous physical activity is important with regard to the quality of life of middle-aged and elderly individuals. The benefits of preventing less time spent in moderate-to-vigorous physical activity were greater than the benefits of more time spent in moderate-to-vigorous physical activity. These results could shift the attention to interventions focused on preventing reductions in moderate-to-vigorous physical activity levels. Further longitudinal studies are needed to confirm these findings and explore causality