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.

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.

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%.

Body weight and premature retirement: population-based evidence from Finland.

BACKGROUND: Health status is a principal determinant of labour market participation. In this study, we examined whether excess weight is associated with withdrawal from the labour market owing to premature retirement. METHODS: The analyses were based on nationally representative data from Finland over the period 2001-15 (N ∼ 2500). The longitudinal data included objective measures of body weight (i.e. body mass index and waist circumference) linked to register-based information on actual retirement age. The association between the body weight measures and premature retirement was modelled using cubic b-splines via logistic regression. The models accounted for other possible risk factors and potential confounders, such as smoking and education. RESULTS: Excess weight was associated with an increased risk of premature retirement for both men and women. A closer examination revealed that the probability of retirement varied across the weight distribution and the results differed between sexes and weight measures. CONCLUSION: Body weight outside a recommended range elevates the risk of premature retirement.

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.

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.

Genetic endowments, parental resources and adult health: Evidence from the Young Finns Study.

This paper uses longitudinal survey data linked to administrative registers to examine socioeconomic gradients in health, particularly whether the effects of genetic endowments interact with the socioeconomic resources of the parental household. We find that genetic risk scores contribute to adult health measured by biomarkers. This result is consistent with the findings from genome-wide association studies. Socioeconomic gradients in health differ based on biomarker and resource measures. Family education is negatively related to obesity and the waist-hip ratio, and family income is negatively related to low-density lipoprotein cholesterol and triglyceride levels. Parental resources do not modify the effects of genetic endowment on adult health. However, there is evidence for gene-family income interactions for triglyceride levels, particularly among women.

Stature and long-term labor market outcomes: Evidence using Mendelian randomization.

We use the Young Finns Study (N=∼2000) on the measured height linked to register-based long-term labor market outcomes. The data contain six age cohorts (ages 3, 6, 9, 12, 15 and 18, in 1980) with the average age of 31.7, in 2001, and with the female share of 54.7. We find that taller people earn higher earnings according to the ordinary least squares (OLS) estimation. The OLS models show that 10cm of extra height is associated with 13% higher earnings. We use Mendelian randomization, with the genetic score as an instrumental variable (IV) for height to account for potential confounders that are related to socioeconomic background, early life conditions and parental investments, which are otherwise very difficult to fully account for when using covariates in observational studies. The IV point estimate is much lower and not statistically significant, suggesting that the OLS estimation provides an upward biased estimate for the height premium. Our results show the potential value of using genetic information to gain new insights into the determinants of long-term labor market success.

Depressive symptoms and long-term income: The Young Finns Study.

BACKGROUND: Higher depressive symptoms have been associated with lower future income. However, studies examining this issue have had limited follow-up times and have used self-reported measures of income. Also, possible confounders or mediators have not been accounted. METHODS: 971 women and 738 men were selected from the ongoing prospective Young Finns Study (YFS) that began in 1980. Depressive symptoms were measured in 1992 when participants were from 15 to 30 years old. Information on annual income and earnings from 1993 to 2010 were obtained from the Finnish Longitudinal Employer-Employee Data (FLEED) of Statistics Finland and linked to the YFS. RESULTS: Higher depressive symptoms were associated with lower future income and earnings. For men, the associations were robust for controlling childhood parental socioeconomic status, history of unemployment, and adulthood health behavior, but attenuated circa 35% when three major temperament traits were taken into account. For women, similar pattern was found, however, in the models adjusted for temperament traits the associations did not remain statistically significant. The association between depressive symptoms and earnings was three times stronger for men than women. LIMITATIONS: Previous depressive episodes could have influenced on some participants' economic and educational choices. CONCLUSIONS: Higher depressive symptoms in adolescence and early adulthood lead to significant future losses of total income and earnings, and this association is particularly strong for men.

Childhood Physical Activity and Adulthood Earnings.

PURPOSE: This study examined the associations between childhood physical activity level and adulthood earnings. METHODS: The data were drawn from the ongoing longitudinal Young Finns Study, which was combined with register-based Finnish Longitudinal Employer-Employee Data and register-based parents' background information from the Longitudinal Population Census of Statistics Finland. The study consisted of children who were 9 yr (n = 1257, 52% boys), 12 yr (n = 1662, 51% boys), and 15 yr (n = 1969, 49% boys) of age at the time when physical activity was measured. The children were followed until 2010, when they were between 33 and 45 yr old. Leisure-time physical activity in childhood was self-reported, whereas earnings in adulthood were register based and covered over a 10-yr period from 2000 to 2010. Ordinary least squares models were used to analyze the relationship between physical activity and earnings. RESULTS: Childhood physical activity level was positively associated with long-term earnings among men (P < 0.001). In more detail, a higher level of leisure-time physical activity at the age of 9, 12, and 15 yr was associated with an approximate 12%-25% increase in average annual earnings over a 10-yr period. The results were robust to controlling, e.g., an individual's chronic conditions and body fat, parents' education and physical activity, and family income. Among women, no relation was observed. CONCLUSIONS: The findings provide evidence that childhood physical activity can have far-reaching positive effects on adulthood earnings. Possibilities for improving physical activity during childhood may not only promote health but also affect long-term labor market outcomes.