Relation Between Leisure Time, Commuting, and Occupational Physical Activity With Blood Pressure in 125 402 Adults:The Lifelines Cohort

Background Whether all domains of daily-life moderate-to-vigorous physical activity (MVPA) are associated with lower blood pressure (BP) and how this association depends on age and body mass index remains unclear. Methods and Results In the population-based Lifelines cohort (N=125 402), MVPA was assessed by the Short Questionnaire to Assess Health-Enhancing Physical Activity, a validated questionnaire in different domains such as commuting, leisure-time, and occupational PA. BP was assessed using the last 3 of 10 measurements after 10 minutes' rest in the supine position. Hypertension was defined as systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or use of antihypertensives. In regression analysis, higher commuting and leisure-time but not occupational MVPA related to lower BP and lower hypertension risk. Commuting-and-leisure-time MVPA was associated with BP in a dose-dependent manner. β Coefficients (95% CI) from linear regression analyses were -1.64 (-2.03 to -1.24), -2.29 (-2.68 to -1.90), and finally -2.90 (-3.29 to -2.50) mm Hg systolic BP for the low, middle, and highest tertile of MVPA compared with "No MVPA" as the reference group after adjusting for age, sex, education, smoking and alcohol use. Further adjustment for body mass index attenuated the associations by 30% to 50%, but more MVPA remained significantly associated with lower BP and lower risk of hypertension. This association was age dependent. β Coefficients (95% CI) for the highest tertiles of commuting-and-leisure-time MVPA were -1.67 (-2.20 to -1.15), -3.39 (-3.94 to -2.82) and -4.64 (-6.15 to -3.14) mm Hg systolic BP in adults 60 years, respectively. Conclusions Higher commuting and leisure-time but not occupational MVPA were significantly associated with lower BP and lower hypertension risk at all ages, but these associations were stronger in older adults

Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety

It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a variety of stress-related exposures on depression and anxiety. We included 41,810 participants with both genome-wide genetic data and measurements of depression and anxiety in the Lifelines Cohort Study. Current depression and anxiety were measured by the MINI International Neuropsychiatric Interview. Stress-related exposures included long-term difficulties, stressful life events, reduced social support, childhood trauma, and loneliness, which were measured by self-report questionnaires. PRSs were calculated based on recent large genome-wide association studies for depression and anxiety. We used linear mixed models adjusting for family relationships to estimate the interactions between PRSs and stress-related exposures. Nine of the ten investigated interactions between the five stress-related exposures and the two PRSs for depression and anxiety were significant (Ps &lt; 0.001). Reduced social support, and higher exposure to long-term difficulties, stressful life events, and loneliness amplified the genetic effects on both depression and anxiety. As for childhood trauma exposure, its interaction with the PRS was significant for depression (P = 1.78 × 10 -05) but not for anxiety (P = 0.32). Higher levels of stress-related exposures significantly amplify the effects of genetic susceptibility on depression and anxiety. With a large sample size and a comprehensive set of stress-related exposures, our study provides powerful evidence on the presence of polygenic risk-by-environment interactions in relation to depression and anxiety. </p

Three facets of planning and postponement of parenthood in the Netherlands

BACKGROUND The age at parenthood has risen by about five years in the last decades in the Netherlands. Previous studies typically focused on the age at which people have their first child, but little is known about desired timing of parenthood and how this desire changes. OBJECTIVE In this study, we examined three facets of postponement: (1) desired age to have a first child, (2) changes in this desired age, and (3) whether the desires are met. METHODS We use data from the Longitudinal Internet Studies for the Social Sciences (N = 2,296), which is a representative sample of men and women in the Netherlands who have been followed for up to ten years. RESULTS Men and women desire to have children at relatively high ages, i.e., around age 30. About half of the respondents update these desires by increasing the desired age as they get older. Half of respondents do not become a parent at their desired time. CONCLUSIONS The high ages at first birth observed are due to a combination of the three facets of postponement. CONTRIBUTION This study contributes to the literature by showing that the high observed age at which people have children nowadays is due to high desired ages, updating these desires upwards, and not achieving their desired timing

Glaucoma in large-scale population-based epidemiology:a questionnaire-based proxy

Purpose: To improve upon self-reported glaucoma status in population-based cohorts by developing a questionnaire-based proxy incorporating self-reported status in conjunction with glaucoma-specific visual complaints. Methods: A vision specific questionnaire, including questions from the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) was administered to 79,866 Lifelines participants, a population-based cohort study in the Northern Netherlands. We compared NEI-VFQ-25 responses between ‘definite’ glaucoma cases (n = 90; self-reported surgical cases) and an age- and gender-matched subset of controls (n = 1,800) to uncover glaucoma-specific visual complaints, using a case–control logistic regression. We defined ‘probable glaucoma’ as both self-reported disease status and visual complaints, and ‘possible glaucoma’ as either. To evaluate the resulting proxy, we determined age-stratified glaucoma prevalences in the remaining cohort and compared the result to the literature. Results: Per unit increase in the vision subscales (range 0–100) distance, peripheral and low luminance, we observed significantly increased odds of definite glaucoma (2% [P = 0.03], 4% [P = 1.2 × 10−8] and 2% [P = 0.02], respectively); the associated area under the curve was 0.73. We identified 300 probable and 3,015 (1,434 by self-report) possible glaucoma cases. Standardised prevalences of definite, probable and possible glaucoma for 55+ were 0.4%, 1.1% and 7.3%, respectively. For self-reported glaucoma (combining definite, probable and possible by self-report), this was 5.2%. Conclusions: The combination of self-reported glaucoma status and visual complaints can be used to capture glaucoma cases in population-based settings. The resulting prevalence of combined definite and probable glaucoma (1.5%) appears to be more consistent with previous reports than the prevalence estimate of 5.2% based only on self-report

Correction:Glaucoma in large-scale population-based epidemiology: a questionnaire-based proxy (Eye, (2021), 35, 2, (508-516), 10.1038/s41433-020-0882-4)

The original version of this article unfortunately contained a mistake. The Acknowledgements section was incorrect. The corrected Acknowledgements section is given below. The original article has been corrected. Acknowledgements This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement EGRET No 661883. The funding organisation had no role in the design, conduct, analysis, or publication of this research. The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University of Groningen and the Northern Provinces of the Netherlands

Prevalence and risk factors of dry eye in 79,866 participants of the population-based Lifelines cohort study in the Netherlands

Purpose: To investigate the prevalence of dry eye among all adult age categories and to discover independent risk factors by investigating a wide range of etiological categories. Methods: A cross-sectional association study including 79,866 voluntary participants aged 20-94 years of the population-based Lifelines Cohort Study in the Netherlands. Results: Overall, 9.1% of participants had dry eye disease as measured by the Women's Health Study dry eye questionnaire. Prevalence of dry eye symptoms were particularly prevalent in 20-30 years olds. Dry eye was associated with comorbidities in almost all body systems, including musculoskeletal, gastro-intestinal, ophthalmic, autoimmune, psychiatric, pain, functional, dermatological and atopic disorders. Numerous independent risk factors were discovered or confirmed, with strong associations for female sex, contact lens use, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, eye surgery including cataract and laser refractive surgery, keratoconus, osteoarthritis, connective tissue diseases, atherosclerosis, Graves' disease, autistic disorder, depression, 'burnout', Crohn's disease, sarcoid, lichen planus, rosacea, liver cirrhosis, sleep apnea, sinusitis, thyroid function, and air pollution (NO2). High blood pressure and high BMI were strongly associated with less dry eye, as was current smoking, while ex-smokers had more dry eye. No clear link between dry eye and lipid or blood glucose levels was found. Conclusions: This study on dry eye confirmed but also refuted many risk factors from smaller epidemiological studies, and discovered numerous new risk factors in multiple etiological categories. The finding that dry eye symptoms are particularly common in young adults is concerning, and warrants further study

Genetic pre-screening for glaucoma in population-based epidemiology:protocol for a double-blind prospective screening study within Lifelines (EyeLife)

BACKGROUND: Early detection of glaucoma is paramount to maintain patients' eyesight, however glaucomatous vision loss tends to begin in the periphery with up to 50% of patients unaware they are affected. Because glaucomatous vision loss is permanent, screening appears attractive, but currently is not cost-effective. Therefore we aim to investigate the utility of genetic pre-screening for glaucoma in a population-based setting, called EyeLife. METHODS: EyeLife adopts a double blind prospective design with contrasting groups. Selected participants (n = 1600) from the Lifelines cohort are 55 years of age or older, and of either the highest or lowest 20% of the genetic risk distribution for glaucoma. We obtained a highly curated list of genetic variants from the literature to obtain each participants' genetic risk for glaucoma. Participants will undergo comprehensive ophthalmic screening. The primary outcome is the relative risk of glaucoma given a high genetic risk compared to a low genetic risk. DISCUSSION: If genetic pre-screening is successful, it will increase the yield of a glaucoma screening program by focusing on high-risk individuals. This, in turn, may improve long-term visual health of middle-aged and elderly people. TRIAL REGISTRATION: Ethics approval was obtained on January 31, 2019, and the study was retrospectively registered with the Netherlands Trial Register ( NL8718 ) on the 17th of June, 2020

Novel genes for QTc interval. How much heritability is explained, and how much is left to find?

The corrected QT (QTc) interval is a complex quantitative trait, believed to be influenced by several genetic and environmental factors. It is a strong prognostic indicator of cardiovascular mortality in patients with and without cardiac disease. More than 700 mutations have been described in 12 genes (LQT1-LQT12) involved in congenital long QT syndrome. However, the heritability (genetic contribution) of QTc interval in the general population cannot be adequately explained by these long QT syndrome genes. In order to further investigate the genetic architecture underlying QTc interval in the general population, genome-wide association studies, in which up to one million single nucleotide polymorphisms are assayed in thousands of individuals, are now being employed and have already led to the discovery of variants in seven novel loci and five loci that are known to cause congenital long or short QT syndrome. Here we show that a combined risk score using 11 of these loci explains about 10% of the heritability of QTc. Additional discovery of both common and rare variants will yield further etiological insight and accelerate clinical applications

Heritability of glaucoma and glaucoma-related endophenotypes:Systematic review and meta-analysis

We have systematically extracted all available heritability (h2) estimates of glaucoma and related endophenotypes from the literature and summarized the evidence by meta-analysis. Glaucoma endophenotypes were classified into 10 clusters: intraocular pressure, anterior chamber size, central corneal thickness, cup-to-disc ratio, disc size, cup size, corneal hysteresis, retinal nerve fiber layer thickness, cup shape, and peripapillary atrophy. Random-effects meta-analyses were performed for each cluster. For clusters with n ≥ 10 h2 estimates, we also performed subgroup and meta-regression analyses. The literature search yielded 53 studies. The h2 of primary open-angle glaucoma ranged from 0.17 to 0.81, and was 0.65 for primary angle-closure glaucoma in a single study. The pooled endophenotype h2 estimates were intraocular pressure, 0.43 (0.38-0.48); anterior chamber size, 0.67 (0.60-0.74); central corneal thickness, 0.81 (0.73-0.87); cup-to-disc ratio, 0.56 (0.44-0.68); disc size, 0.61 (0.37-0.81); cup size, 0.58 (0.35-0.78); corneal hysteresis, 0.40 (0.29-0.51); retinal nerve fiber layer thickness, 0.73 (0.42-0.91); cup shape, 0.62 (0.22-0.90); and peripapillary atrophy, 0.73 (0.70-0.75). We identified mean age, ethnicity, and study design as major sources of heterogeneity. Our results confirm the strong influence of genetic factors on glaucoma and its endophenotypes. These pooled h2 estimates provide the most accurate assessment to date of the total genetic variation that can ultimately be explained by gene-finding studies