C-reactive Protein and Temperament: An Instrumental Variable Analysis

BACKGROUND: Temperament is associated with circulating inflammatory biomarkers, such as C-reactive protein (CRP), which has been associated with various health conditions, including depression. This study aims to investigate whether genetic disposition for increased circulating CRP concentration may influence temperament over the life-course. METHODS: Using a longitudinal cohort that began in 1980—the Cardiovascular Risk in Young Finns Study (YFS)—we included 920 participants (59.8% female) aged 3–12 years old at baseline (childhood), and the same participants again at ages 30–39 years old (adulthood) in this study. We used both ordinary least-squares regression (OLS linear regression) and instrumental variable (IV) regression to assess associations between CRP concentration and temperament dimensions (negative emotionality, activity, and sociability). To represent genetically determined risk for increase in circulating CRP concentration, we calculated a weighted genetic risk score (GRS) which reflects risk for increased circulating CRP concentration. RESULTS: In OLS linear regression analyses, we found that increased circulating CRP concentration in childhood was associated with slightly higher scores for sociability in childhood (19% increase, CI ​= ​7–32%) and adulthood (13% increase, CI ​= ​2–27%), and lower activity scores in adulthood (15% decrease, CI ​= ​3–25%). For all IV regressions, there were no apparent associations between GRS and temperament in either childhood or adulthood (all p>0.3). The Durbin-Wu-Hausman test for endogeneity produced p-values (all>0.05) that suggest there is no evidence for disagreement between the OLS and IV estimates. CONCLUSIONS: We found no clear evidence for an association of GRS for elevated CRP with childhood or adulthood emotionality, activity, or sociability, although circulating CRP was associated with some of these traits

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, inferences based on genetic instruments showed that higher education leads to better choices in some but not all dimensions of health behaviors

Response by Hakala et al to Letter Regarding Article, "Cardiovascular Risk Factor Trajectories Since Childhood and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study"

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The serum copper/zinc ratio in childhood and educational attainment: a population-based study

BACKGROUND: Micronutrients are potentially important determinants of adult outcomes such as educational attainment. Copper and zinc have known effects on several medical conditions and cognitive development. Elevated copper and depressed zinc is a common trace metal imbalance. METHODS: We estimate the correlation between the copper/zinc ratio (Cu/Zn) in childhood (year 1980) and educational attainment in adulthood (year 2010). We use the Young Finns Study (YFS) combined with the Finnish Linked Employer-Employee Data (FLEED). The regression models account for confounders such as other biomarkers and parental observables. RESULTS: We report a sizeable, negative correlation between Cu/Zn and educational attainment as measured by education in years, grades as well as the likelihood of completing university education. For example, a one standard deviation increase in Cu/Zn decreases the probability of university education by ∼4%. CONCLUSIONS: The findings are consistent with a Cu/Zn effect influencing cognitive functioning early in life. Future research should explore more deeply the precise mechanisms by which Cu/Zn affects educational attainment

Changes in BMI and physical activity from youth to adulthood distinguish normal-weight, metabolically obese adults from those who remain healthy

Highlights: Adults with MONW have a lower BMI during youth until young adulthood, but higher BMI after this than adults with metabolically healthy normal weight. Adults with MONW have a greater decrease in physical activity from youth to adulthood than other adults. Healthy lifestyle is important in the prevention of metabolic disorders, particularly in individuals who are slim in childhood. Background: Individuals with metabolically obese normal-weight (MONW) have higher risk of cardiovascular events than those with obesity but a metabolically healthy status. Etiological factors leading to MONW are not well known. We hypothesized distinct trajectories of changes in BMI and physical activity may modify metabolic risk and distinguish individuals with MONW from those who remain healthy. Methods: We compared the mean levels of BMI and physical activity at eight time points (1980, 1983, 1986, 1989, 1992, 2001, 2007, 2011) between MONW and healthy normal-weight adults using linear mixed-model analysis. The analyses included 1180 participants of the Cardiovascular Risk in Young Finns study, a population-based study that represents six different age cohorts 3, 6, 9, 12, 15 and 18 years of age at baseline. Results: Individuals with adult MONW had significantly lower BMI in childhood and young adulthood, but their BMI increased more than in other adults after this age (p<0.001for interaction between time and MONW status). Physical activity decreased relatively more since youth in individuals with adult MONW (p<0.001). Conclusions: Relative leanness in youth and subsequent weight gain in young adulthood, and a gradual decrease in physical activity levels from youth to adulthood, predispose normal-weight individuals to metabolic impairments. The results highlight the importance of a healthy lifestyle in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.publishedVersionPeer reviewe

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.</p

Increase in adiposity from childhood to adulthood predicts a metabolically obese phenotype in normal-weight adults

Normal weight is associated with a favorable cardiometabolic risk profile and low risk of type 2 diabetes and cardiovascular disease. However, some normal-weight individuals—the “metabolically obese normal weight” (MONW)—show a cardiometabolic risk profile similar to the obese. Previous studies have shown that older age, central body fat distribution, and unfavorable lifestyle increase the risk of MONW. However, the role of early-life factors in MONW remains unknown. We examined the associations of early-life factors with adult MONW in 1178 individuals from the Cardiovascular Risk in Young Finns study who were followed up from childhood to adulthood. The strongest early predictor for adult MONW was an increase in BMI from childhood to adulthood (p = 3.1 × 10−11); each 1 SD increase in BMI z-score from childhood to adulthood led to a 2.56-fold increase in the risk of adult MONW (CI 95% = 1.94–3.38). Other significant predictors of adult MONW were male sex (OR = 2.38, 95% = 1.63–3.47, p = 7.0 × 10−6), higher childhood LDL cholesterol (OR = 1.41 per 1 SD increase in LDL cholesterol, CI 95% = 1.14–1.73, p = 0.001), and lower HDL cholesterol (OR = 1.51 per 1 SD decrease in HDL cholesterol, CI 95% = 1.23–1.85, p = 5.4 × 10−5). Our results suggest that an increase in adiposity from childhood to adulthood is detrimental to cardiometabolic health, even among individuals remaining normal weight.</p

Geographic origin as a determinant of left ventricular mass and diastolic function - the Cardiovascular Risk in Young Finns Study

Aims: Eastern Finns have higher risk of coronary heart disease (CHD) and carotid intima-media thickness than western Finns although current differences in CHD risk factors are minimal. Left ventricular (LV) mass and diastolic function predict future cardiovascular events but their east-west differences are unknown. We examined the association of eastern/western baseline origin with LV mass and diastolic function. Methods : The study population included 2045 subjects of the Cardiovascular Risk in Young Finns Study with data from the baseline survey (1980) and the latest follow-up (2011) when echocardiography was performed at the age of 34-49 years. Results: Subjects with eastern baseline origin had in 2011 higher LV mass (139 +/- 1.0 vs. 135 +/- 1.0 g, p=0.006) and E/e-ratio indicating weaker LV diastolic function (4.86 +/- 0.03 vs. 4.74 +/- 0.03, p=0.02) than western subjects. Results were independent of age, sex, area of examination and CHD risk factors such as blood pressure and BMI (LV mass indexed with height: pPeer reviewe

Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study

Alms Mendelian randomization uses genetic variants related to environmentally modifiable risk factors in an attempt to improve causal inference from observational data. We examined the effect of lifetime body mass index (BMI) on adult carotid intima-media thickness (CIMT) and various atherosclerotic risk factors by using both Mendelian randomization and conventional analyses.Methods and results A total of 2230 individuals (1218 women), aged 3-18 at study induction, took part in clinical examinations in 1980, 1983, 1986, and, most recently, 2001 when they were aged 24-39. In these analyses we utilized the known relation between FTO polymorphism rs9939609 and BMI. The dose-response association between the number of A alleles in FTO and higher mean BMI from childhood to adulthood was confirmed, but no associations with potential confounding factors were observed. In standard regression models, lifetime BMI was associated with adult CIMT, lifetime systolic blood pressure, adult fasting glucose, and adult HOMA-index. When variation in FTO was used as an instrument for unconfounded BMI levels, similar or larger effects of lifetime BMI on all these phenotypes were found, although with wider confidence intervals.Conclusion Mutually supportive results from Mendelian randomization and standard regression models strengthen the evidence of the effect of lifetime BMI on atherosclerosis risk in young adults

Changes in BMI and physical activity from youth to adulthood distinguish normal-weight, metabolically obese adults from those who remain healthy

HighlightsAdults with MONW have a lower BMI during youth until young adulthood, but higher BMI after this than adults with metabolically healthy normal weight. Adults with MONW have a greater decrease in physical activity from youth to adulthood than other adults. Healthy lifestyle is important in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.BackroundIndividuals with metabolically obese normal-weight (MONW) have higher risk of cardiovascular events than those with obesity but a metabolically healthy status. Etiological factors leading to MONW are not well known. We hypothesized distinct trajectories of changes in BMI and physical activity may modify metabolic risk and distinguish individuals with MONW from those who remain healthy.MethodsWe compared the mean levels of BMI and physical activity at eight time points (1980, 1983, 1986, 1989, 1992, 2001, 2007, 2011) between MONW and healthy normal-weight adults using linear mixed-model analysis. The analyses included 1180 participants of the Cardiovascular Risk in Young Finns study, a population-based study that represents six different age cohorts 3, 6, 9, 12, 15 and 18 years of age at baseline.ResultsIndividuals with adult MONW had significantly lower BMI in childhood and young adulthood, but their BMI increased more than in other adults after this age (pConclusionsRelative leanness in youth and subsequent weight gain in young adulthood, and a gradual decrease in physical activity levels from youth to adulthood, predispose normal-weight individuals to metabolic impairments. The results highlight the importance of a healthy lifestyle in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.</p