Effect of weight on depression using multiple genetic instruments.

A striking global health development over the past few decades has been the increasing prevalence of overweight and obesity. At the same time, depression has become increasingly common in almost all high-income countries. We investigated whether body weight, measured by body mass index (BMI), has a causal effect on depression symptoms in Finland. Using data drawn from the Cardiovascular Risk in Young Finns Study (N = 1,523, mean age 41.9, SD 5), we used linear regression to establish the relationship between BMI and depression symptoms measured by 21-item Beck's Depression Inventory. To identify causal relationships, we used the Mendelian randomization (MR) method with weighted sums of genetic markers (single nucleotide polymorphisms, SNPs) as instruments for BMI. We employ instruments (polygenic risk scores, PGSs) with varying number of SNPs that are associated with BMI to evaluate the sensitivity of our results to instrument strength. Based on linear regressions, higher BMI was associated with a higher prevalence of depression symptoms among females (b = 0.238, p = 0.000) and males (b = 0.117, p = 0.019). However, the MR results imply that the positive link applies only to females (b = 0.302, p = 0.007) but not to males (b = -0.070, p = 0.520). Poor instrument strength may explain why many previous studies that have utilized genetic instruments have been unable to identify a statistically significant link between BMI and depression-related traits. Although the number of genetic markers in the instrument had only a minor effect on the point estimates, the standard errors were much smaller when more powerful instruments were employed.

Effect of Information Intervention on Prescribing Practice for Neuropathic Pain in Older Patients: A Nationwide Register-Based Study.

INTRODUCTION: Management of prescription medicines is challenging for older patients due to frail health and the prevalence of multiple chronic conditions. A salient policy challenge of prescribing practices is that all physicians are not well informed about the national clinical guidelines. A feasible policy intervention to mitigate the harms caused by Potentially Inappropriate Medications is to influence the frequency of prescribing and other prescribing attributes of the drugs by providing accurate and up-to-date information about the national clinical guidelines. OBJECTIVES: The objective of this study was to examine the effect of a nationwide information intervention on physicians' prescribing practices and patients' healthcare utilization. METHODS: We used a quasi-experimental research design based on difference-in-differences variation and nationwide register data on prescribers and purchasers of pregabalin, nortriptyline, and amitriptyline combinations in Finland between January 2018 and May 2019. The study included 68,914 patients and 11,432 physicians. RESULTS: We found that the information letter sent to all prescribers of pregabalin, nortriptyline, or amitriptyline combinations to patients aged 75 years or older decreased the probability of prescribing of these medications. The estimated effect of - 3.3 percentage points (95% confidence interval [- 0.041, - 0.024]) corresponds to a 29% reduction compared to the baseline mean of the outcome. The filled quantity, measured in Defined Daily Doses, of pregabalin, nortriptyline, and amitriptyline combinations per month was reduced by 11.7% [- 14.5% to - 8.9%] among patients aged 75 years or older. No effect on patients' healthcare utilization was observed. CONCLUSIONS: Findings of the study suggest that personal information intervention was an effective policy tool for nudging physicians to reduce prescribing of potentially inappropriate medicines, whereas the reduction in prescribing was not accompanied by improvements or adverse effects in patients' health.

The Time-Varying Effect of Participatory Shift Scheduling on Working Hour Characteristics and Sickness Absence: Evidence from a Quasi-Experiment in Hospitals.

Participatory shift scheduling for irregular working hours can influence shift schedules and sickness absence. We investigated the effects of using participatory shift scheduling and shift schedule evaluation tools on working hour characteristics and sickness absence. We utilized a panel data for 2015-2019 with 16,557 hospital employees (6143 in the intervention and 10,345 in the control group). Difference-in-differences regression with ward-level clustered standard errors was used to estimate the average treatment effect on the treated coefficients relative to timing of the intervention with 95% confidence intervals (CI). Using participatory scheduling tool increased long working hours and weekend work and had delayed effects on the short (1-3 days) sickness absences. Increased effects were observed: 0.2 [95% CI 0.0-0.4] days for the second, and 0.8 [95% CI 0.5-1.0] for the third year after the onset of intervention. An average increase of 0.5 [95% CI 0.1-0.9] episodes on all sickness absence episodes was observed for the third year. Using the shift schedule evaluation tool with the participatory shift scheduling tool attenuated the adverse effects. To conclude, participatory shift scheduling increased some potentially harmful working hour characteristics but its effects on sickness absence were negligible, and further attenuated by using the shift schedule evaluation tool.

Schizophrenia polygenic risk score and long-term success in the labour market: A cohort study.

Employment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our results indicate that individuals with schizophrenia or schizophrenia-related traits have a weakened ability to fully participate in the labour market, potentially reinforcing social exclusion.

Economic burden of low physical activity and high sedentary behaviour in Finland.

BACKGROUND: Low physical activity and high sedentary behaviour are unquestionably relevant for public health while also increasing direct and indirect costs. METHODS: The authors examined the direct and indirect costs attributable to low physical activity and high sedentary behaviour in Finland in 2017. Costs related to major non-communicable diseases drawn from Finnish registries covered direct costs (outpatient visits, days of inpatient care, medication and institutional eldercare) and indirect costs (sickness-related absences, disability pensions, unemployment benefits, all-cause mortality and losses of income tax revenue). Prevalences of low physical activity and high sedentary behaviour (≥8 hours per 16 waking hours) were based on self-reports among adolescents or accelerometer data among adults and the elderly from three Finnish population studies: FINFIT 2017, Health 2011 and the Cardiovascular Risk in Young Finns Study. Cost calculations used adjusted population attributable fractions (PAF) and regression models. Total annual costs were obtained by multiplying PAF by the total costs of the given disease. RESULTS: The total costs of low physical activity in Finland in 2017 came to approximately €3.2 billion, of which direct costs accounted for €683 million and indirect ones for €2.5 billion. Costs attributable to high sedentary behaviour totalled roughly €1.5 billion. CONCLUSION: The findings suggest that low physical activity and high sedentary behaviour levels create substantial societal costs. Therefore, actions intended to increase physical activity and reduce excessive sedentary behaviour throughout life may yield not only better health but also considerable savings to society.

Does better education mitigate risky health behavior? A mendelian randomization study.

Education and risky health behaviors are strongly negatively correlated. Education may affect health behaviors by enabling healthier choices through higher disposable income, increasing information about the harmful effects of risky health behaviors, or altering time preferences. Alternatively, the observed negative correlation may stem from reverse causality or unobserved confounders. Based on the data from the Cardiovascular Risk in Young Finns Study linked to register-based information on educational attainment and family background, this paper identifies the causal effect of education on risky health behaviors. To examine causal effects, we used a genetic score as an instrument for years of education. We found that individuals with higher education allocated more attention to healthy habits. In terms of health behaviors, highly educated people were less likely to smoke. Some model specifications also indicated that the highly educated consumed more fruit and vegetables, but the results were imprecise in this regard. No causal effect was found between education and abusive drinking. In brief, inference based on genetic instruments showed that higher education leads to better choices in some but not all dimensions of health behaviors.

Birth weight, adult weight, and cardiovascular biomarkers: Evidence from the Cardiovascular Young Finns Study.

This study quantifies the causal effect of birth weight on cardiovascular biomarkers in adulthood using the Cardiovascular Risk in Young Finns Study (YFS). We apply a multivariable Mendelian randomization (MVMR) method that provides a novel approach to improve inference in causal analysis based on a mediation framework. The results show that birth weight is linked to triglyceride levels (ß = -0.294; 95% CI [-0.591, 0.003]) but not to low-density lipoprotein (LDL) cholesterol levels (ß = 0.007; 95% CI [-0.168, 0.183]). The total effect of birth weight on triglyceride levels is partly offset by a mediation pathway linking birth weight to adult BMI (ß = 0.111; 95% CI [-0.013, 0.234]). The negative total effect is consistent with the fetal programming hypothesis. The positive indirect effect via adult BMI highlights the persistence of body weight throughout a person's life and the adverse effects of high BMI on health. The results are consistent with previous findings that both low birth weight and weight gain increase health risks in adulthood.

Birth weight and adult income: An examination of mediation through adult height and body mass.

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%.

Childhood physical activity as a labor market investment.

This study examined the role of physical activity and changes in physical activity levels during childhood in long-term labor market outcomes. To address this important but under-researched theme, the study utilized data drawn from longitudinal research, the Cardiovascular Risk in Young Finns Study (YFS), and from registries compiled by Statistics Finland. The study consisted of children aged 9 (n = 1565) and 15 (n = 2445) at the time their physical activity was measured. Labor market outcomes, including employment status, average employment months, and average unemployment months, were calculated from 1997 to 2010, when the participants were aged 20 to 48 years. Regression models were used to assess the relationship between physical activity and labor market outcomes. The results show that the consequences of childhood physical activity may be far-reaching, as higher childhood physical activity was positively related to the probability of being employed and employment months and was negatively related to unemployment months. On average, a one-unit increase in physical activity index was related to a 1% higher probability of being employed, 0.10 more months of yearly employment, and 0.05 fewer months of yearly unemployment. The results also imply that persistently active individuals had the highest level of employment and the lowest level of unemployment compared with other activity groups. In conclusion, investments in childhood physical activity may not only promote health and well-being but may also correlate with better labor market outcomes later in life, providing both personal and societal benefits.

The effects of using participatory working time scheduling software on sickness absence: A difference-in-differences study.

BACKGROUND: Participatory working time scheduling is a collaborative approach to scheduling shift work. As a potential way of improving work time control, it may provide a means to reducing sickness absence in shift work. So far, experimental and quasi-experimental studies on the effects of increased work time control on sickness absence are lacking. OBJECTIVE: To investigate the effects of using digital participatory working time scheduling software on ward-level sickness absence among Finnish hospital employees. PARTICIPANTS AND METHODS: This quasi-experimental study compared the amount of sickness absence in hospital wards using a participatory working time scheduling software (n=121 wards) and those continuing with traditional working time scheduling (n=117 wards) between 2014 and 2017. We used continuous panel data from 238 hospital wards with a total number of 9000 hospital employees (89% of women, primarily nursing staff). The ward-level measures consisted of number of employees, working hours, sickness absence spells per employee, and short (1-3) sickness absence days per employee. Two-way fixed effects and event study regressions with clustered standard errors were used to estimate the effect of using participatory scheduling software on sickness absence. RESULTS: Sickness absence spells and short (1-3) sickness absence days decreased by 6% and 7%, respectively in the wards using participatory scheduling compared to those using traditional scheduling. The effect became stronger as the time measured in quarters of using the participatory working time scheduling software increased. CONCLUSIONS: The effects of using participatory working time scheduling software indicated less ward-level sickness absence measured as spells and days in comparison to continuing with traditional scheduling. The encouraging findings are relevant not only to the health care sector but also to other sectors in which irregular shift work is a necessity. This study was registered with ClinicalTrials.gov (NCT02775331) before starting the intervention phase.

Education leads to a more physically active lifestyle: Evidence based on Mendelian randomization.

Physical inactivity is a major health risk worldwide. Observational studies suggest that higher education is positively related to physical activity, but it is not clear whether this relationship constitutes a causal effect. Using participants (N = 1651) drawn from the Cardiovascular Risk in Young Finns Study linked to nationwide administrative data from Statistics Finland, this study examined whether educational attainment, measured by years of education, is related to adulthood physical activity in terms of overall physical activity, weekly hours of intensive activity, total steps per day, and aerobic steps per day. We employed ordinary least squares (OLS) models and extended the analysis using an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. Based on the MR results, it was found that years of education is positively related to physical activity. On average, one additional year of education leads to a 0.62-unit higher overall physical activity (P < .01), 0.26 more hours of weekly intensive activity (P < .05), 560 more steps per day (P < .10), and 390 more aerobic steps per day (P < .09). The findings indicate that education may be a factor leading to higher leisure-time physical activity and thus promoting global health.

Do childhood infections affect labour market outcomes in adulthood and, if so, how?

A burgeoning body of literature suggests that poor childhood health leads to adverse health outcomes, lower educational attainment and weaker labour market outcomes in adulthood. We focus on an important but under-researched topic, which is the role played by infection-related hospitalization (IRH) in childhood and its links to labour market outcomes later in life. The participants aged 24-30 years in 2001 N = 1706 were drawn from the Young Finns Study, which includes comprehensive registry data on IRHs in childhood at ages 0-18 years. These data are linked to longitudinal registry information on labour market outcomes (2001-2012) and parental background (1980). The estimations were performed using ordinary least squares (OLS). The results showed that having an additional IRH is associated with lower log earnings (b = -0.110, 95 % confidence interval (CI): -0.193; -0.026), fewer years of being employed (b = -0.018, 95 % CI: -0.031; -0.005), a higher probability of receiving any social income transfers (b = 0.012, 95 % CI: -0.002; 0.026) and larger social income transfers, conditional on receiving any (b = 0.085, 95 % CI: 0.025; 0.145). IRHs are negatively linked to human capital accumulation, which explains a considerable part of the observed associations between IRHs and labour market outcomes. We did not find support for the hypothesis that adult health mediates the link.

Health endowment and later-life outcomes in the labour market: Evidence using genetic risk scores and reduced-form models.

This paper examines the relationship between health endowment and later-life outcomes in the labour market. The analysis is based on reduced-form models in which labour market outcomes are regressed on genetic variants related to the increased risk of cardiovascular diseases. We use linked Finnish data that have many strengths. Genetic risk scores constitute exogenous measures for health endowment, and accurate administrative tax records on earnings, employment and social income transfers provide a comprehensive account of an individual's long-term performance in the labour market. The results show that although the direction of an effect is generally consistent with theoretical reasoning, the effects of health endowment on outcomes are statistically weak, and the hypothesis of no effect can be rejected only in one case: genetic endowment related to obesity influences male earnings and employment in prime age. Due to the sample size (N = 1651), the results should be interpreted with caution and should be confirmed in larger samples and in other institutional settings.

The effect of weight on labor market outcomes: An application of genetic instrumental variables.

This paper contributes to the literature on the labor market consequences of obesity by using a novel instrument: genetic risk score, which reflects the predisposition to higher body mass index (BMI) across many genetic loci. We estimate instrumental variable models of the effect of BMI on labor market outcomes using Finnish data that have many strengths, for example, BMI that is measured rather than self-reported, and data on earnings and social income transfers that are from administrative tax records and are thus free of the problems associated with nonresponse, reporting error or top coding. The empirical results are sensitive to whether we use a narrower or broader genetic risk score, and to model specification. For example, models using the narrower genetic risk score as an instrument imply that a one-unit increase in BMI is associated with 6.9% lower wages, 1.8% fewer years employed, and a 3 percentage point higher probability of receiving any social income transfers. However, when we use a newer, broader genetic risk score, we cannot reject the null hypothesis of no effect. Future research using genetic risk scores should examine the sensitivity of their results to the risk score used.

Does education protect against depression? Evidence from the Young Finns Study using Mendelian randomization.

Using participants (N = 1733) drawn from the nationally representative longitudinal Young Finns Study (YFS) we estimate the effect of education on depressive symptoms. In 2007, when the participants were between 30 and 45 years old, they reported their depressive symptoms using a revised version of Beck's Depression Inventory. Education was measured using register information on the highest completed level of education in 2007, which was converted to years of education. To identify a causal relationship between education and depressive symptoms we use an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. The genetic risk score was based on 74 genetic variants, which were associated with years of education in a genome-wide association study (GWAS). Because the genetic variants are randomly assigned at conception, they induce exogenous variation in years of education and thus identify a causal effect if the assumptions of the MR approach are met. In Ordinary Least Squares (OLS) estimation years of education in 2007 were negatively associated with depressive symptoms in 2007 (b = -0.027, 95% Confidence Interval (CI) = -0.040, -0.015). However, the results based on Mendelian randomization suggested that the effect is not causal (b = 0.017; 95% CI = -0.144, 0.178). This indicates that omitted variables correlated with education and depression may bias the linear regression coefficients and exogenous variation in education caused by differences in genetic make-up does not seem to protect against depressive symptoms.

Gene-environment interactions between education and body mass: Evidence from the UK and Finland.

More education is associated with a lower body mass index (BMI) and likelihood of being overweight. However, since a large proportion of the variation in body mass is due to genetic makeup, it has been hypothesized that education may moderate the genetic risk. We estimate main associations between (i) education, (ii) genetic risk, and (iii) interactions between education and genetic risk on BMI and the probability of being overweight in the UK and Finland. The estimates show that education is negatively associated with BMI and overweightness, and genetic risk is positively associated. However, the interactions between education and genetic risk are small and statistically insignificant.

Longitudinal Associations between Physical Activity and Educational Outcomes.

PURPOSE: This longitudinal study examined the role of leisure-time physical activity in academic achievement at the end of compulsory basic education and educational attainment in adulthood. METHODS: The data were drawn from the ongoing longitudinal Cardiovascular Risk in Young Finns Study, which was combined with register-based data from Statistics Finland. The study consisted of children who were 12 yr (n = 1723, 49% boys) and 15 yr (n = 2445, 48% boys) of age at the time when physical activity was measured. The children were followed up until 2010, when their mean age was 40 yr. Physical activity was self-reported and included several measurements: overall leisure-time physical activity outside school hours, participation in sports club training sessions, and participation in sports competitions. Individuals' educational outcomes were measured with the self-reported grade point average at age 15 yr and register-based information on the years of completed postcompulsory education in adulthood. Ordinary least squares models and the instrumental variable approach were used to analyze the relationship between physical activity and educational outcomes. RESULTS: Physical activity in adolescence was positively associated with educational outcomes. Both the physical activity level at age 15 yr and an increase in the physical activity level between the ages of 12 and 15 yr were positively related to the grade point average at age 15 yr and the years of postcompulsory education in adulthood. The results were robust to the inclusion of several individual and family background factors, including health endowments, family income, and parents' education. CONCLUSION: The results provide evidence that physical activity in adolescence may not only predict academic success during compulsory basic education but also boost educational outcomes later in life.

The biometric antecedents to happiness.

It has been suggested that biological markers are associated with human happiness. We contribute to the empirical literature by examining the independent association between various aspects of biometric wellbeing measured in childhood and happiness in adulthood. Using Young Finns Study data (n = 1905) and nationally representative linked data we examine whether eight biomarkers measured in childhood (1980) are associated with happiness in adulthood (2001). Using linked data we account for a very rich set of confounders including age, sex, body size, family background, nutritional intake, physical activity, income, education and labour market experiences. We find that there is a negative relationship between triglycerides and subjective well-being but it is both gender- and age-specific and the relationship does not prevail using the later measurements (1983/1986) on triglycerides. In summary, we conclude that none of the eight biomarkers measured in childhood predict happiness robustly in adulthood.

Does higher education protect against obesity? Evidence using Mendelian randomization.

OBJECTIVES: The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. METHODS: Participants (N=2011) were from the on-going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m2) measurements in 2007 and 2011 and genetic information were linked to comprehensive register-based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome-wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects. RESULTS: The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b)=-0.22; 95% Confidence Intervals [CI]=-0.29, -0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b=-0.84; 95% CI=-1.77, 0.09). CONCLUSION: The findings indicate that education could be a protective factor against obesity in advanced countries.