Overcoming attenuation bias in regressions using polygenic indices.

Measurement error in polygenic indices (PGIs) attenuates the estimation of their effects in regression models. We analyze and compare two approaches addressing this attenuation bias: Obviously Related Instrumental Variables (ORIV) and the PGI Repository Correction (PGI-RC). Through simulations, we show that the PGI-RC performs slightly better than ORIV, unless the prediction sample is very small (N < 1000) or when there is considerable assortative mating. Within families, ORIV is the best choice since the PGI-RC correction factor is generally not available. We verify the empirical validity of the simulations by predicting educational attainment and height in a sample of siblings from the UK Biobank. We show that applying ORIV between families increases the standardized effect of the PGI by 12% (height) and by 22% (educational attainment) compared to a meta-analysis-based PGI, yet estimates remain slightly below the PGI-RC estimates. Furthermore, within-family ORIV regression provides the tightest lower bound for the direct genetic effect, increasing the lower bound for the standardized direct genetic effect on educational attainment from 0.14 to 0.18 (+29%), and for height from 0.54 to 0.61 (+13%) compared to a meta-analysis-based PGI.

Examining neighborhood effects on mental health utilizing a novel two-stage modeling approach.

PURPOSE: Neighborhood conditions may affect health, but health may also determine a preference for where to live. This study estimates the effect of neighborhood characteristics on mental health while aiming to adjust for this residential self-selection. METHODS: A two-step method was implemented using register data from Statistics Netherlands from all residents of the city of Rotterdam relocating within the city in 2013 (N = 12,456). First, using a conditional logit model, we estimated for each individual the probability of relocating to a neighborhood over all other neighborhoods in Rotterdam, based on personal and neighborhood characteristics in 2013. Second, we corrected this selection process in a model investigating the effects of neighborhood characteristics in 2014 on reimbursed anti-depressant or anti-psychotic medication in 2016. RESULTS: Personal and neighborhood characteristics predicted neighborhood choice, indicating strong patterns of selection into neighborhoods. Unadjusted for selection log neighborhood income was associated with reimbursed medication (ß = -0.040, 95% CI = -0.060, -0.020), but the association strongly attenuated after controlling for self-selection into neighborhoods (ß = -0.010, 95% CI = -0.030, 0.011). The opposite was observed for contact with neighbors; unadjusted for self-selection there was no association (ß = -0.020, 95% CI = -0.073, 0.033), but after adjustment increased neighborhood contact was associated with an 8.5% relative reduction in reimbursed medication (ß = -0.075, 95% CI = -0.126, -0.025). CONCLUSIONS: The method illustrated in this study offers new opportunities to disentangle selection from causation in neighborhood health research.

Rank concordance of polygenic indices.

Polygenic indices (PGIs) are increasingly used to identify individuals at risk of developing disease and are advocated as screening tools for personalized medicine and education. Here we empirically assess rank concordance between PGIs created with different construction methods and discovery samples, focusing on cardiovascular disease and educational attainment. We find Spearman rank correlations between 0.17 and 0.93 for cardiovascular disease, and 0.40 and 0.83 for educational attainment, indicating highly unstable rankings across different PGIs for the same trait. Potential consequences for personalized medicine and gene-environment (G × E) interplay are illustrated using data from the UK Biobank. Simulations show how rank discordance mainly derives from a limited discovery sample size and reveal a tight link between the explained variance of a PGI and its ranking precision. We conclude that PGI-based ranking is highly dependent on PGI choice, such that current PGIs do not have the desired precision to be used routinely for personalized intervention.

Needs and preferences of women with prior severe preeclampsia regarding app-based cardiovascular health promotion.

BACKGROUND: Women with prior severe preeclampsia are at an increased risk for cardiovascular diseases later in life compared to women who had a normotensive pregnancy. The objective of this study was to assess their needs and preferences regarding app-based cardiovascular health promotion. METHODS: Patients (n = 35) of the Follow-Up PreEClampsia Outpatient Clinic (FUPEC), Erasmus MC, the Netherlands, participated in an anonymous online survey. The main outcomes under study were women's needs for health behavior promotion, and their preferences with respect to intervention delivery. Descriptive statistics were used to evaluate needs, and thematic analysis was used to analyze preferences. RESULTS: Women's primary need for health behavior promotion pertained to their fat and sugar intake and physical activity; for some, to their mental health (practices), fruit and vegetable intake, salt intake, and water intake; and for a few, to their alcohol and tobacco use. Most women preferred an app-based intervention to include, in descending order: the tracking of health-related metrics, an interactive platform, the use of behavior change strategies, the provision of information, and personalization. CONCLUSION: Cardiovascular health promotion targeting women with prior severe preeclampsia should feel relevant to its audience. App-based interventions are likely to be well received if they target fat and sugar intake and physical activity. These interventions should preferably track health-related metrics, be interactive, contain behavior change strategies, provide information, and be personalized. Adopting these findings during intervention design could potentially increase uptake, behavior change, and behavior change maintenance in this population.

Perceived determinants of physical activity among women with prior severe preeclampsia: a qualitative assessment.

BACKGROUND: The objective of this study was to (1) qualitatively identify the perceived determinants of physical activity among women who have experienced severe preeclampsia, and (2) examine whether these determinants are consistent with the overarching processes outlined in the integrated behavior change (IBC) model, a novel model that describes physical activity as being a result of motivational, volitional, and automatic processes. METHODS: Patients (n = 35) of the Follow-Up PreEClampsia (FUPEC) Outpatient Clinic, Erasmus MC, the Netherlands, participated in an anonymous online survey. The main outcomes under study were their perceived determinants of physical activity. Responses were analyzed using thematic analysis. RESULTS: Thirteen themes emerged from the analysis. Six themes corresponded with motivational processes (future health, perceived ability, attitude, future reward or regret, physical appearance, and doing it for others), two with volitional processes (scheduling and planning), and two with automatic processes (affect and stress). Three themes were classified as environmental factors (time constraint, social support, and physical environment). CONCLUSIONS: A range of facilitating and hindering factors were described by women with prior severe preeclampsia as the determinants of their physical activity. These factors corresponded well with the overarching motivational, volitional, and automatic processes described in the IBC model. In addition, motivational and environmental factors beyond the IBC model were described. Addressing these perceived determinants could enhance the efficacy of physical activity interventions in this population. TWEETABLE ABSTRACT: Motivational, volitional, automatic, and environmental factors drive physical activity in women with prior severe preeclampsia.

Moving from intention to behaviour: a randomised controlled trial protocol for an app-based physical activity intervention (i2be).

INTRODUCTION: Efficacy tests of physical activity interventions indicate that many have limited or short-term efficacy, principally because they do not sufficiently build on theory-based processes that determine behaviour. The current study aims to address this limitation. METHODS AND ANALYSIS: The efficacy of the 8-week intervention will be tested using a three-condition randomised controlled trial delivered through an app, in women with a prior hypertensive pregnancy disorder. The intervention is based on the integrated behaviour change model, which outlines the motivational, volitional and automatic processes that lead to physical activity. The mechanisms by which the behaviour change techniques lead to physical activity will be tested.Following stratification on baseline factors, participants will be randomly allocated in-app to one of three conditions (1:1:1). The information condition will receive information, replicating usual care. Additionally to what the information condition receives, the motivation condition will receive content targeting motivational processes. Additionally to what the motivation condition receives, the action condition will receive content targeting volitional and automatic processes.The primary outcome is weekly minutes of moderate-to-vigorous physical activity, as measured by an activity tracker (Fitbit Inspire 2). Secondary outcomes include weekly average of Fitbit-measured daily resting heart rate, and self-reported body mass index, waist-hip ratio, cardiorespiratory fitness and subjective well-being. Tertiary outcomes include self-reported variables representing motivational, volitional, and automatic processes. Outcome measures will be assessed at baseline, immediately post-intervention, and at 3 and 12 months post-intervention. Physical activity will also be investigated at intervention midpoint. Efficacy will be determined by available case analysis. A process evaluation will be performed based on programme fidelity and acceptability measures. ETHICS AND DISSEMINATION: The Medical Ethics Committee of the Erasmus MC has approved this study (MEC-2020-0981). Results will be published in peer reviewed scientific journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: Netherlands trial register, NL9329.

The Interplay between Maternal Smoking and Genes in Offspring Birth Weight.

It is well-established that both the child's genetic endowments as well as maternal smoking during pregnancy impact offspring birth weight. In this paper we move beyond the nature versus nurture debate by investigating the interaction between genetic endowments and this critical prenatal environmental exposure - maternal smoking - in determining birth weight. We draw on longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) study and replicate our results using data from the UK Biobank. Genetic endowments of the children are proxied with a polygenic score that is constructed based on the results of the most recent genome-wide association study of birth weight. We instrument the maternal decision to smoke during pregnancy with a genetic variant (rs1051730) located in the nicotine receptor gene CHRNA3. This genetic variant is associated with the number of cigarettes consumed daily, and we present evidence that this is plausibly the only channel through which the maternal genetic variant affects the child's birth weight. Additionally, we deal with the misreporting of maternal smoking by using measures of cotinine, a biomarker of nicotine, collected from the mother's urine during their pregnancy. We confirm earlier findings that genetic endowments as well as maternal smoking during pregnancy significantly affects the child's birth weight. However, we do not find evidence of meaningful interactions between genetic endowments and an adverse fetal environment, suggesting that the child's genetic predisposition cannot cushion the damaging effects of maternal smoking.

A Theory of Socio-economic Disparities in Health over the Life Cycle.

Motivated by the observation that medical care explains only a relatively small part of the SES-health gradient, we present a life-cycle model that incorporates several additional behaviours that potentially explain (jointly) a large part of observed disparities. As a result, the model provides not only a conceptual framework for the SES-health gradient but more generally an improved framework for the production of health. We derive novel predictions from the theory by performing comparative dynamic analyses. More generally, our comparative dynamic method can be applied to models of similar form, e.g., human capital, health deficits, firm investment, to name a few.

Consumer Preferences and Demand for Annuities: Evidence From Hong Kong.

Retirees without annuities in Hong Kong confront longevity and investment risks. Despite these risks, there is very limited uptake of annuities. This study identifies product and consumer characteristics that are associated with the demand for annuities in Hong Kong. We conduct a discrete choice experiment and distribute a consumer survey among two independent representative samples of workers aged between 40 and 64. Results suggest that a fixed monthly income and a 10-year guarantee period are two significant product characteristics, while a bequest motive, being married, and an understanding of the annuity are consumer characteristics that are associated with the demand for annuities. Being presented the optimal hypothetical annuity product, approximately one-third of middle-aged workers choose to annuitize their retirement savings. The findings and methods of this study can be applied for designing annuity products in other contexts.

Pleiotropy-robust Mendelian randomization.

Background: The potential of Mendelian randomization studies is rapidly expanding due to: (i) the growing power of genome-wide association study (GWAS) meta-analyses to detect genetic variants associated with several exposures; and (ii) the increasing availability of these genetic variants in large-scale surveys. However, without a proper biological understanding of the pleiotropic working of genetic variants, a fundamental assumption of Mendelian randomization (the exclusion restriction) can always be contested. Methods: We build upon and synthesize recent advances in the literature on instrumental variables (IVs) estimation that test and relax the exclusion restriction. Our pleiotropy-robust Mendelian randomization (PRMR) method first estimates the degree of pleiotropy, and in turn corrects for it. If (i) a subsample exists for which the genetic variants do not affect the exposure; (ii) the selection into this subsample is not a joint consequence of the IV and the outcome; (iii) pleiotropic effects are homogeneous, PRMR obtains unbiased estimates of causal effects. Results: Simulations show that existing MR methods produce biased estimators for realistic forms of pleiotropy. Under the aforementioned assumptions, PRMR produces unbiased estimators. We illustrate the practical use of PRMR by estimating the causal effect of: (i) tobacco exposure on body mass index (BMI); (ii) prostate cancer on self-reported health; and (iii) educational attainment on BMI in the UK Biobank data. Conclusions: PRMR allows for instrumental variables that violate the exclusion restriction due to pleiotropy, and it corrects for pleiotropy in the estimation of the causal effect. If the degree of pleiotropy is unknown, PRMR can still be used as a sensitivity analysis.

Efficiency of Health Investment: Education or Intelligence?

In this paper, we hypothesize that education is associated with a higher efficiency of health investment, yet that this efficiency advantage is solely driven by intelligence. We operationalize efficiency of health investment as the probability of dying conditional on a certain hospital diagnosis and estimate a multistate structural equation model with three states: (i) healthy, (ii) hospitalized, and (iii) death. We use data from a Dutch cohort born around 1940 that links intelligence tests at age 12 years to later-life hospitalization and mortality records. The results indicate that intelligent individuals have a clear survival advantage for most hospital diagnoses, while the remaining disparities across education groups are small and not statistically significant. © 2016 The Authors. Health Economics Published by John Wiley & Sons Ltd.

Education and health: The role of cognitive ability.

We aim to disentangle the relative impact of (i) cognitive ability and (ii) education on health and mortality using a structural equation model suggested by Conti et al. (2010). We extend their model by allowing for a duration dependent variable (mortality), and an ordinal educational variable. Data come from a Dutch cohort born between 1937 and 1941, including detailed measures of cognitive ability and family background in the final grade of primary school. The data are linked to the mortality register 1995-2011, such that we observe mortality between ages 55 and 75. The results suggest that at least half of the unconditional survival differences between educational groups are due to a 'selection effect', primarily on the basis of cognitive ability. Conditional survival differences across those having finished just primary school and those entering secondary education are still substantial, and amount to a 4 years gain in life expectancy, on average.

Self-Employment and Health: Barriers or Benefits?

The self-employed are often reported to be healthier than wageworkers; however, the cause of this health difference is largely unknown. The longitudinal nature of the US Health and Retirement Study allows us to gauge the plausibility of two competing explanations for this difference: a contextual effect of self-employment on health (benefit effect), or a health-related selection of individuals into self-employment (barrier effect). Our main finding is that the selection of comparatively healthier individuals into self-employment accounts for the positive cross-sectional difference. The results rule out a positive contextual effect of self-employment on health, and we present tentative evidence that, if anything, engaging in self-employment is bad for one's health. Given the importance of the self-employed in the economy, these findings contribute to our understanding of the vitality of the labor force. Copyright © 2014 John Wiley & Sons, Ltd.

Wealth and Health Behavior: Testing the Concept of a Health Cost.

Wealthier individuals engage in healthier behavior. This paper seeks to explain this phenomenon by exploiting both inheritances and lottery winnings to test a theory of health behavior. We distinguish between the direct monetary cost and the indirect health cost (value of health lost) of unhealthy consumption. The health cost increases with wealth and the degree of unhealthiness, leading wealthier individuals to consume more healthy and moderately unhealthy, but fewer severely unhealthy goods. The empirical evidence presented suggests that differences in health costs may indeed partially explain behavioral differences, and ultimately health outcomes, between wealth groups.

The contribution of occupation to health inequality.

Health is distributed unequally by occupation. Workers on a lower rung of the occupational ladder report worse health, have a higher probability of disability and die earlier than workers higher up the occupational hierarchy. Using a theoretical framework that unveils some of the potential mechanisms underlying these disparities, three core insights emerge: (i) there is selection into occupation on the basis of initial wealth, education, and health, (ii) there will be behavioural responses to adverse working conditions, which can have compensating or reinforcing effects on health, and (iii) workplace conditions increase health inequalities if workers with initially low socioeconomic status choose harmful occupations and don't offset detrimental health effects. We provide empirical illustrations of these insights using data for the Netherlands and assess the evidence available in the economics literature.

Long Term and Spillover Effects of Health Shocks on Employment and Income.

We use matching combined with difference-in-differences to identify the causal effects of sudden illness, represented by acute hospitalizations, on employment and income up to six years after the health shock using linked Dutch hospital and tax register data. An acute hospital admission lowers the employment probability by seven percentage points and results in a five percent loss of personal income two years after the shock. There is no subsequent recovery in either employment or income. There are large spillover effects: household income falls by 50 percent more than the income of the disabled person.

Health Inequalities through the Lens of Health Capital Theory: Issues, Solutions, and Future Directions.

We explore what health-capital theory has to offer in terms of informing and directing research into health inequality. We argue that economic theory can help in identifying mechanisms through which specific socioeconomic indicators and health interact. Our reading of the literature, and our own work, leads us to conclude that non-degenerate versions of the Grossman model (1972a;b) and its extensions can explain many salient stylized facts on health inequalities. Yet, further development is required in at least two directions. First, a childhood phase needs to be incorporated, in recognition of the importance of childhood endowments and investments in the determination of later-life socioeconomic and health outcomes. Second, a unified theory of joint investment in skill (or human) capital and in health capital could provide a basis for a theory of the relationship between education and health.

Socioeconomic differences in health over the life cycle in an Egalitarian country.

A strong cross-sectional relationship between health and socioeconomic status is firmly established. This paper adopts a life cycle perspective to investigate whether the socioeconomically disadvantaged, on top of a lower health level, experience a sharper deterioration of health over time. Data are drawn from the Dutch Central Bureau of Statistics (CBS) Health Interview Surveys covering the period 1983-2000. The analysis focuses on the self-rated health and disability of persons aged 16-80. We show that in the Netherlands, as in the US, the socioeconomic gradient in health widens until late-middle age and narrows thereafter. The analysis and the available evidence suggests that the widening gradient is attributable both to health-related withdrawal from the labor force, resulting in lower incomes, and the cumulative protective effect of education on health outcomes. The less educated appear to suffer a double health penalty in that they begin adult life with a slightly lower health level, which subsequently declines at a faster rate.

Health and income across the life cycle and generations in Europe.

An age-cohort decomposition applied to panel data identifies how the mean, overall inequality and income-related inequality of self-assessed health evolve over the life cycle and differ across generations in 11 EU countries. There is a moderate and steady decline in mean health until the age of 70 or so and a steep acceleration in the rate of deterioration thereafter. In southern Europe and Ireland, where development has been most rapid, the average health of generations born in more recent decades is significantly better than that of older generations. This is not observed in the northern European countries. In almost all countries, health is more dispersed among older generations indicating that Europe has experienced a reduction in overall health inequality over time. Although there is no consistent evidence that health inequality increases as a given cohort ages, this is true in the three largest countries--UK, France and Germany. In the former two countries and the Netherlands, at least for males, the income gradient in health peaks around retirement age, as in the US. In most European countries, unlike the US, there is no evidence that income-related health inequality is greater among younger than older generations.