Genetic basis of STEM occupational choice and regional economic performance: a UK biobank genome-wide association study.

BACKGROUND: Science, technology, engineering, and mathematics (STEM) professionals are regarded as the highly skilled labor force that fosters economic productivity, enterprise innovation, and international competitiveness of a country. This study aims to understand the genetic predisposition to STEM occupations and investigate its associations with regional economic performance. We conducted a genome-wide association study on the occupational choice of STEM jobs based on a sample of 178,976 participants from the UK Biobank database. RESULTS: We identified two genetic loci significantly associated with participants' STEM job choices: rs10048736 on chromosome 2 and rs12903858 on chromosome 15. The SNP heritability of STEM occupations was estimated to be 4.2%. We also found phenotypic and genetic evidence of assortative mating in STEM occupations. At the local authority level, we found that the average polygenic score of STEM is significantly and robustly associated with several metrics of regional economic performance. CONCLUSIONS: The current study expands our knowledge of the genetic basis of occupational choice and potential regional disparities in socioeconomic developments.

School achievement in adolescence and the risk of mental disorders in early adulthood: a Finnish nationwide register study.

School grades in adolescence have been linked to later psychiatric outcomes, but large-scale nationwide studies across the spectrum of mental disorders are scarce. In the present study, we examined the risk of a wide array of mental disorders in adulthood, as well as the risk of comorbidity, associated with school achievement in adolescence. We used population-based cohort data comprising all individuals born in Finland over the period 1980-2000 (N = 1,070,880) who were followed from age 15 or 16 until a diagnosis of mental disorder, emigration, death, or December 2017, whichever came first. Final grade average from comprehensive school was the exposure, and the first diagnosed mental disorder in a secondary healthcare setting was the outcome. The risks were assessed with Cox proportional hazards models, stratified Cox proportional hazard models within strata of full-siblings, and multinomial regression models. The cumulative incidence of mental disorders was estimated using competing risks regression. Better school achievement was associated with a smaller risk of all subsequent mental disorders and comorbidity, except for eating disorders, where better school achievement was associated with a higher risk. The largest associations were observed between school achievement and substance use disorders. Overall, individuals with school achievement more than two standard deviations below average had an absolute risk of 39.6% of a later mental disorder diagnosis. By contrast, for individuals with school achievement more than two standard deviations above average, the absolute risk of a later mental disorder diagnosis was 15.7%. The results show that the largest mental health burden accumulates among those with the poorest school achievement in adolescence.

The rare disease neurofibromatosis 1 as a source of hereditary economic inequality: Evidence from Finland.

PURPOSE: This study investigated whether individuals with neurofibromatosis 1 (NF1) fare worse than individuals without NF1 in terms of economic well-being. NF1 is relatively common in the population and provides an informative case of a rare hereditary disease. METHODS: We examined a subset of 692 individuals with verified NF1 from the Finnish total population-based NF1 cohort and compared that with 7407 control individuals matched for age, sex, and municipality during 1997-2014. Economic well-being was operationalized with annual work earnings and total income, including social income transfers. RESULTS: NF1 significantly worsened economic well-being. Low education, increased morbidity, and reduced labor market participation partly explained the effect of NF1. Yet, NF1 was independently associated with lower income even after adjusting for these factors. Furthermore, NF1 had a larger negative effect on income from work than it had on total income, which indicated that the Finnish social security system partly compensated the labor market losses suffered by individuals with NF1. NF1 had a larger impact on economic inequality for men than for women. CONCLUSION: NF1 contributes to economic inequality. A hereditary disease may convey worse economic well-being over several generations.

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.

A rare disease and education: Neurofibromatosis type 1 decreases educational attainment.

Rare heritable syndromes may affect educational attainment. Here, we study education in neurofibromatosis 1 (NF1) that is associated with multifaceted medical, social and cognitive consequences. Educational attainment in the Finnish population-based cohort of 1408 individuals with verified NF1 was compared with matched controls using Cox proportional hazards model with delayed entry and competing risk for death. Moreover, models accounting for the effects of cancer at age 15-30 years, parental NF1 and developmental disorders were constructed. Overall, the attainment of secondary education was reduced in individuals with NF1 compared to controls (hazard ratio 0.83, 95%CI 0.74-0.92). History of cancer and developmental disorders were major predictors of lack of secondary education. Individuals with NF1 obtained vocational secondary education more often than general upper secondary education. Consequently, NF1 decreased the attainment of Bachelor's and Master's degrees by 46%-49% and 64%-74%, respectively. Surprisingly, the non-NF1 siblings of individuals with NF1 also had lower educational attainment than controls, irrespective of parental NF1. In conclusion, NF1 is associated with reduced educational attainment and tendency for affected individuals to obtain vocational instead of academic education. Individuals living with NF1, especially those with cancer, developmental disorders or familial NF1, need effective student counseling and learning assistance.

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.

Employment and earnings trajectories before and after sickness absence due to major depressive disorder: a nationwide case-control study.

OBJECTIVES: To examine employment and earnings trajectories before and after the first sickness absence period due to major depressive disorder (MDD). METHODS: All individuals (n=158 813) in Finland who had a first sickness absence period (lasting longer than 9 days) due to MDD between 2005 and 2015 were matched with one randomly selected individual of the same age and gender with no history of MDD. Employment status and earnings were measured using register-based data annually from 2005 to 2015. Generalised estimating equations were used to examine the trajectories of employment and earnings before and after MDD diagnosis in men and women separately. RESULTS: Sickness absence due to MDD was associated with increased probability of non-employment during and after the year of the first sickness absence period. In men, but not in women, the probability of being employed was lower 5 years before the sickness absence period due to MDD. When compared with the individuals in the control group, men had around 34% and women 15% lower earnings 1 year, and 40% and 23%, respectively, 5 years, after the first sickness absence period due to MDD. More severe MDD and longer duration of sickness absence period were associated with lower probability of being employed. CONCLUSIONS: Sickness absence due to MDD was associated with considerable reduction in employment and earnings losses. For men and individuals with more severe MDD, this reduction was before the first sickness period. This supports a reciprocal association between employment and earnings with MDD.

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.

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.

Unfit for work: Health and labour-market prospects.

AIM: The aim of this study was to examine whether health status (number of chronic diseases, health shock and use of tranquilizers/sleeping pills) is related to labour-market outcomes later in life. METHODS: Twin data for Finnish men and women who were at least 33 years old in 1990 were linked to comprehensive register-based information on unemployment and the incidence of disability pension. We used the within-twin dimension of the data to account for shared family and genetic factors. Self-reported information on the number of diagnosed chronic diseases, health shock and drug use were obtained from the 1975 and 1981 twin surveys, when the twins were at least 18 years old. Unemployment months and the incidence of disability pension were measured during prime working age over the 1990-2004/2009 period. RESULTS: Poor health status is significantly positively related to unemployment and the incidence of disability pension. The results are robust to controlling for shared family and genetic factors and the key measures of risky health behaviours (alcohol use, lifetime smoking and body mass index). CONCLUSIONS: Health status is a fundamental determinant of long-term labour-market outcomes.

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.

Alcohol Consumption and Long-Term Labor Market Outcomes.

This paper examines whether alcohol consumption is related to long-term labor market outcomes. We use twin data for Finnish men and women matched to register-based individual information on employment and earnings. The twin data allow us to account for the shared environmental and genetic factors. The quantity of alcohol consumption was measured by weekly average consumption using self-reported data from three surveys (1975, 1981 and 1990). The average of an individual's employment months and earnings were measured in adulthood over the period 1990-2009. The models that account for the shared environmental and genetic factors reveal that former drinkers and heavy drinkers both have almost 20% lower earnings compared with moderate drinkers. On average, former drinkers work annually approx. 1 month less over the 20-year observation period. These associations are robust to the use of covariates, such as education, pre-existing health endowment and smoking. Copyright © 2015 John Wiley & Sons, Ltd.

Devil in disguise: Does drinking lead to a disability pension?

OBJECTIVES: To examine whether alcohol consumption in adulthood is related to the incidence of receiving a disability pension later in life. METHODS: Twin data for Finnish men and women born before 1958 were matched to register-based individual information on disability pensions. Twin differences were used to eliminate both shared environmental and genetic factors. The quantity of alcohol consumption was measured as the weekly average consumption using self-reported data from three surveys (1975, 1981 and 1990). The disability pension data were evaluated from 1990-2004. RESULTS: The models that account for shared environmental and genetic factors reveal that heavy drinkers are significantly more likely to receive a disability pension than moderate drinkers or constant abstainers. Heavy drinking that leads to passing out is also positively related to receiving a disability pension. The results were robust to the use of potential confounders that twins do not share, such as education years, the number of chronic diseases, physical activity at work and leisure, and stressful life events. CONCLUSION: Drinking profiles in early adulthood are an important predictor of receiving a disability pension later in life.

Smoking and long-term labour market outcomes.

OBJECTIVE: To examine the long-term effects of smoking on labour market outcomes using twin data matched to register-based individual information on earnings. METHOD: Twin data for Finnish men born 1945-1957 was used to remove the shared environmental and genetic factors. The results were subjected to extensive robustness testing. Lifetime cigarette consumption was measured by (cumulative) cigarette pack-years in early adulthood. The average of an individual's earnings (and, alternatively, taxable income) was measured over a subsequent 15-year period in later adulthood. RESULTS: Smokers have lower long-term income and earnings. For example, controlling for the shared environmental and genetic factors using the data on genetically identical twins, smoking is negatively associated with lifetime income (p=0.015). The negative association was also robust to the use of various covariates, such as education, health indicators and extraversion. CONCLUSIONS: Smoking is negatively related to long-term labour market outcomes. The provision of information about the indirect monetary costs of smoking may thus complement the policy efforts that aim at educating consumers about the health costs of smoking.

Effects of nurse visit copayment on primary care use: Do low-income households pay the price?

Nurses are increasingly providing primary care, yet the literature on cost-sharing has paid little attention to nurse visits. We employ a staggered difference-in-differences design to examine the effects of adopting a 10-euro copayment for nurse visits on the use of public primary care among Finnish adults. We find that the copayment reduced nurse visits by 9%-10% during a one-year follow-up. There is heterogeneity by income in absolute terms, but not in relative terms. The spillover effects on general practitioner (GP) use are negative but small, with varying statistical significance. We also analyze the subsequent nationwide abolition of the copayment. However, we refrain from drawing causal conclusions from this due to the lack of credibility in the parallel trends assumption. Overall, our analysis suggests that moderate copayments can create a greater barrier to access for low-income individuals. We also provide an example of using a pre-analysis plan for retrospective observational data.

The contribution of morbidity and unemployment for the reduced labor market participation of individuals with neurofibromatosis 1 in Finland.

Neurofibromatosis 1 (NF1) is a multisystem disorder associated with, for example, a high risk for cancer, a variety of behavioral and cognitive deficits, low educational attainment and decreased income. We now examined the labor market participation of individuals with NF1. We analyzed the numbers of days of work, unemployment, and sickness allowance among 742 Finnish individuals with NF1 aged 20-59 years using nationwide register data from Statistics Finland and the Social Insurance Institution of Finland. The individuals with NF1 were compared with a control cohort of 8716 individuals matched with age, sex, and the area of residence. Individuals with NF1 had a significantly lower number of working days per year than the controls (rate ratio [RR] 0.93, 95% CI 0.91-0.95). Unemployment (RR 1.79, 95% CI 1.58-2.02), and sickness absence (RR 1.44, 95% CI 1.25-1.67) were more frequent in the NF1 than in the control group. The causes of sickness allowances were highly concordant with the previously reported morbidity profile of NF1 including neoplasms, cardiovascular disease, mental and behavioral diseases, and neurological diseases. In conclusion, NF1 significantly interferes with labor market participation via both unemployment and morbidity. Unemployment seems to cause more days of not working than sickness absence.

Transmission of Mental Disorders in Adolescent Peer Networks.

Importance: Previous research indicates that mental disorders may be transmitted from one individual to another within social networks. However, there is a lack of population-based epidemiologic evidence that pertains to the full range of mental disorders. Objective: To examine whether having classmates with a mental disorder diagnosis in the ninth grade of comprehensive school is associated with later risk of being diagnosed with a mental disorder. Design, Setting, and Participants: In a population-based registry study, data on all Finnish citizens born between January 1, 1985, and December 31, 1997, whose demographic, health, and school information were linked from nationwide registers were included. Cohort members were followed up from August 1 in the year they completed ninth grade (approximately aged 16 years) until a diagnosis of mental disorder, emigration, death, or December 31, 2019, whichever occurred first. Data analysis was performed from May 15, 2023, to February 8, 2024. Exposure: The exposure was 1 or more individuals diagnosed with a mental disorder in the same school class in the ninth grade. Main Outcomes and Measures: Being diagnosed with a mental disorder during follow-up. Results: Among the 713 809 cohort members (median age at the start of follow-up, 16.1 [IQR, 15.9-16.4] years; 50.4% were males), 47 433 had a mental disorder diagnosis by the ninth grade. Of the remaining 666 376 cohort members, 167 227 persons (25.1%) received a mental disorder diagnosis during follow-up (7.3 million person-years). A dose-response association was found, with no significant increase in later risk of 1 diagnosed classmate (HR, 1.01; 95% CI, 1.00-1.02), but a 5% increase with more than 1 diagnosed classmate (HR, 1.05; 95% CI, 1.04-1.06). The risk was not proportional over time but was highest during the first year of follow-up, showing a 9% increase for 1 diagnosed classmate (HR, 1.09; 95% CI, 1.04-1.14), and an 18% increase for more than 1 diagnosed classmate (HR, 1.18; 95% CI, 1.13-1.24). Of the examined mental disorders, the risk was greatest for mood, anxiety, and eating disorders. Increased risk was observed after adjusting for an array of parental, school-level, and area-level confounders. Conclusions and Relevance: The findings of this study suggest that mental disorders might be transmitted within adolescent peer networks. More research is required to elucidate the mechanisms underlying the possible transmission of mental disorders.

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.