Education as a moderator of genetic risk for higher body mass index: prospective cohort study from childhood to adulthood.

OBJECTIVES: The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI. SUBJECTS/METHODS: The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood. RESULTS: Mean BMI increased from 22.6 to 26.6 kg/m2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P<0.001)). The association between the genetic risk score and BMI was more pronounced among those with lower educational level in adulthood (b=-0.12 (95% CI, -0.23-0.01); P=0.036)). No interaction effect was observed between the genetic risk score and parental education (b=0.05 (95% CI, -0.09-0.18; P=0.51)). Diet and physical activity explained little of the interaction effect between the genetic risk score and adulthood education. CONCLUSIONS: In this prospective study, the association of a risk score of 97 genetic variants with BMI was stronger among those with low compared with high education. This suggests lower education in adulthood accentuates the risk of higher BMI in people at genetic risk.

Associations of temporal and energetic characteristics of behavior with depressive symptoms: A population-based longitudinal study within Strelau's Regulative Theory of Temperament.

BACKGROUND: Individual dispositions have previously been associated with increased risk for depressive symptoms. The direction of the association has been found to be sometimes reciprocal. We examined whether temperament traits are associated with depressive symptoms and whether depressive symptoms contribute to changes in temperament. METHODS: Participants (n=674-811) were from a population-based Young Finns Study. Temperament was assessed by a Finnish version of the Formal Characteristics of Behavior - Temperament Inventory. Depressive symptoms were assessed with modified BDI (mBDI) in 1997, 2001, 2007 and 2012, and BDI-II in 2012. RESULTS: Higher perseveration and emotional reactivity were associated with higher level of depressive symptoms, and higher endurance was associated with lower level of depressive symptoms in 2007 and 2012. These associations were independent of several potential confounders and baseline depressive symptoms. The results of cross-lagged structural equation modeling showed that the associations between temperament and depressive symptoms were reciprocal: briskness, endurance and activity decreased the risk for depressive symptoms while depressive symptoms decreased the level of these characteristics. Perseveration, emotional reactivity and depressive symptoms reinforced each other over time. LIMITATIONS: The depressive symptoms scales we used are not meant for measuring clinically diagnosed depression. The relationships between temperament traits and depressive symptoms were not strong enough to provide a clinical basis for guiding treatment. CONCLUSIONS: Lower perseveration, lower emotional reactivity and higher endurance seem to be health protective temperament characteristics that reduce the risk for depressive symptoms. The reciprocal associations between temperament and depressive symptoms imply mutual health protective and health declining effects. Clinical relevance of the study is that enhancing positive loops and self-concept, and supporting individual stress management might be helpful in prevention of depressive symptoms.

Depressive symptoms are associated with lower bone mineral density in young adults with high job strain. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Job strain has been associated with depressive symptoms, and depression has been associated with low bone mineral density (BMD). PURPOSE: The associations between BMD and job strain have not been studied. We examined the relations between BMD, job strain, and depressive symptoms in a population-based group of young adults in Finland. METHOD: Ultrasonic measurement of BMD at the calcaneus was performed on 777 participants (men 45 %, aged 30-45) drawn from the Cardiovascular Risk in Young Finns Study. Job strain was assessed by self-administered questionnaires by the combination of job demands and job control. Depressive symptoms were assessed with a modified Beck Depression Inventory. The effects of job strain on BMD were studied with multivariable analyses with age, sex, BMI, vitamin D, and calcium intake, physical activity, cigarette smoking, alcohol use, and depressive symptoms as covariates. RESULTS: Depressive symptoms were independently associated with lower BMD T score in participants with high job strain (ß = -0.241, p = 0.02), but depressive symptoms were not significantly associated with BMD in the low (ß = -0.160, p = 0.26) and intermediate (ß = -0.042, p = 0.66) job strain categories. CONCLUSION: The results suggest that job strain modifies the association between depressive symptoms and BMD. Depressed individuals with high work-related stress might be in increased risk of lower bone mineral density.

Childhood family factors predict developmental trajectories of hostility and anger: a prospective study from childhood into middle adulthood.

BACKGROUND: Low socio-economic status (SES), and a conflictive, cold and unsupportive family environment in childhood have been associated with early adulthood hostility. However, it is unknown whether this association changes in magnitude with age from childhood to adulthood. We investigated whether childhood family factors (SES and parental child-rearing style) predicted differential development of offspring hostility and anger from early to middle adulthood. METHOD: Between 2041 and 2316 participants (age range 3-18 years at baseline) were selected from the longitudinal Young Finns study. The participants were followed for 27 years between 1980 and 2007. Childhood SES and parent's self-reported child-rearing style were measured twice: at baseline and 3 years after baseline. Hostility and anger were assessed with self-report questionnaires at 12, 17, 21 and 27 years after baseline. RESULTS: Low parental SES and hostile child-rearing style at baseline predicted higher mean levels of offspring anger and hostility. Low parental SES and one of the hostile child-rearing style components (strict disciplinary style) became more strongly associated with offspring hostility with age, suggesting an accumulating effect. CONCLUSIONS: Childhood family factors predict the development of hostility and anger over 27 years and some of these family factors have a long-term accumulating effect on the development of hostility.

Longitudinal course of depressive symptoms in adulthood: linear stochastic differential equation modeling.

BACKGROUND: Although many studies have addressed the topic of stability versus change in depressive symptoms, few have further decomposed the change to continuous accumulation versus non-systematic state fluctuations or measurement errors. This further step requires a longitudinal follow-up and an appropriate stochastic model; it would, for example, evaluate the hypothesis that women accumulate more susceptibility events than men. Method A linear stochastic differential equation model was estimated for a 16-year longitudinal course of depressive symptoms in the Young Finns community sample of 3596 participants (1832 women, 1764 men). This model enabled us to decompose the variance in depression symptoms into a stable trait, cumulative effects and state/error fluctuations. RESULTS: Women showed higher mean levels and higher variance of depressive symptoms than men. In men, the stable trait accounted for the majority [61%, 90% confidence interval (CI) 48.9-69.2] of the total variance, followed by cumulative effects (23%, 90% CI 9.9-41.7) and state/error fluctuations (16%, 90% CI 5.6-23.2). In women, the cumulative sources were more important than among men and accounted for 44% (90% CI 23.6-58.9) of the variance, followed by stable individual differences (32%, 90% CI 18.5-54.2) and state fluctuations (24%, 90% CI 19.1-27.3). CONCLUSIONS: The results are consistent with previous observations that women suffer more depression than men, and have more variance in depressive symptoms. We also found that continuously accumulating effects are a significant contributor to between-individual differences in depression, especially for women. Although the accumulating effects are often confounded with non-systematic state fluctuations, the latter are unlikely to exceed 27% of the total variance of depressive symptoms.

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phase 1 and 30-45 years at phase 4) in 982-1780 participants depending on the hostility measure. Few promising areas from chromosome 14 at 99 cM (top SNPs rs3783337, rs7158754, rs3783332, rs2181102, rs7159195, rs11160570, rs941898, P values <3.9 × 10(-8) with nearest gene Enah/Vasp-like (EVL)) were found suggestively to be related to paranoia and from chromosome 7 at 86 cM (top SNPs rs802047, rs802028, rs802030, rs802026, rs802036, rs802025, rs802024, rs802032, rs802049, rs802051, P values <6.9 × 10(-7) with nearest gene CROT (carnitine O-octanoyltransferase)) to cynicism, respectively. Some shared suggestive genetic influence for both paranoia and cynicism was also found from chromosome 17 at 2.8 cM (SNPs rs12936442, rs894664, rs6502671, rs7216028) and chromosome 22 at 43 cM (SNPs rs7510759, rs7510924, rs7290560), with nearest genes RAP1 GTPase activating protein 2 (RAP1GAP2) and KIAA1644, respectively. These suggestive associations did not replicate across all measurement times, which warrants further study on these SNPs in other populations.

Sustained involvement in youth sports activities predicts reduced chronic job strain in early midlife.

OBJECTIVE: We examined the long-term effects of youth leisure time physical activity (LTPA) and sports participation on the prevalence of chronic work stress in adulthood. METHODS: Participants (326 men and 338 women) aged 9 to 18 years were initially enrolled in 1980 and followed until 2007. Data were collected using questionnaires and bicycle ergometry in a subgroup. RESULTS: High youth LTPA and sports participation predicted lower chronic job strain in both sexes. The association was mediated by type A leadership. Participation and persistence in organized youth sports followed a similar pattern. In the subgroup, adult physical fitness only partly accounted for the association. CONCLUSIONS: Sustained involvement in youth physical activity and sport lasting at least 3 years is associated with reduced chronic job strain in adulthood. The association was partially explained by type A leadership and physical fitness.

The benefits of sustained leisure-time physical activity on job strain.

BACKGROUND: The long-term effects of leisure-time physical activity (LTPA) on job strain have not been assessed in a large prospective population-based cohort study. AIMS: To examine the relationship between the LTPA and the prevalence of job strain. METHODS: The participants were 861 full-time employees (406 men and 455 women), aged 24-39 years in 2001, from the ongoing Cardiovascular Risk in Young Finns Study. LTPA was assessed using a self-report questionnaire in 1992 and in 2001. The participants were grouped into four categories according to tertiles of LTPA index at two time points: persistently active, increasingly active, decreasingly active and persistently inactive. Job strain was measured in 2001 by indicators of job demands and job control. RESULTS: Baseline LTPA was inversely associated with job strain (P < 0.001) and job demands (P < 0.05) and directly associated with job control (P < 0.05) in both sexes in a model adjusted for the change in 9-year LTPA, age, educational level, occupational status and smoking. Compared with persistently active participants, persistently inactive participants had a 4.0-fold higher job strain after adjustment for the confounders. Similarly, persistently inactive participants had a 2.7-fold higher job demands and a 1.8-fold lower job control. Decreasing physical activity was independently associated with high job strain (P < 0.01) and with low job control (P < 0.01). CONCLUSIONS: Participation in regular LTPA during leisure may help young adults to cope with job strain. A long-term benefit of LTPA may play a role in the development of mental well-being.

Serotonin receptor genes 5HT1A and 5HT2A modify the relation between childhood temperament and adulthood hostility.

We examined a modifying role of 5HT1A and 5HT2A receptors in the relation between childhood difficult temperament and adulthood hostility in 729 subjects derived from a population-based sample. Subjects were 3-12 years when their childhood temperaments consisting of hyperactivity, low sociability and negative emotionality (i.e. the difficult temperament), were assessed by their mothers. Their adulthood hostility comprising anger, cynicism and paranoia, was measured twice, 17 and 21 years later. It was found that the 5HT1A and 5HT2A receptors were not related to childhood temperament or to adult hostility, but they modified the association between childhood hyperactivity and adult hostility in men. Male carriers of T/T genotype of 5HTR2A who were rated hyperactive by their mothers expressed a high level of hostility, especially that of cynicism, in adulthood. For men with other genetic variants, such an association was not seen. This finding was consistent across the two follow-ups 4 years apart. Further research is needed to clarify whether mother-related hyperactivity adequately describes the temperament of the child or is a reflection of mother's hostile child-rearing attitudes.

When do social inequalities in C-reactive protein start? A life course perspective from conception to adulthood in the Cardiovascular Risk in Young Finns Study.

BACKGROUND: It is unclear when in the life course do social inequalities in inflammation emerge. We examined whether the association between socioeconomic position (SEP) and C-reactive protein (CRP) is determined at conception, in childhood, adolescence or adulthood in 1484 participants from the population-based Cardiovascular Risk in Young Finns Study. METHODS: Five variants of the CRP gene were used to investigate whether SEP differences in CRP levels are determined at conception. SEP and serum CRP were assessed in childhood (age 3-9), adolescence (age 12-18) and in adulthood (age 24-39). SEP was measured using parental education and occupational status in childhood and adolescence, and participants' own education and occupational status in adulthood. Participants with CRP > 10 mg/l were excluded. RESULTS: All CRP gene variants were associated with circulating CRP concentrations in childhood, but there were no differences in the distribution of these variants by SEP. No strong evidence was found of associations between parental SEP and CRP. A graded association between higher SEP and lower CRP was observed in adulthood for education (P = 0.0005) but not for occupational status. Trajectories that led to high educational achievement both in the participants and their parents were associated with lower (P

Socioeconomic position in childhood and adult cardiovascular risk factors, vascular structure, and function: cardiovascular risk in young Finns study.

OBJECTIVE: To examine the association of childhood socioeconomic position (SEP) with adult cardiovascular risk factors, vascular structure, and vascular function in a contemporary population of young adults. DESIGN: Population based prospective cohort study with baseline assessment in 1980. SETTING: Finland. PARTICIPANTS: 856 men and 1066 women whose childhood SEP was determined by parental occupational status (manual, lower non-manual, upper non-manual) at age 3-18 years. MAIN OUTCOME MEASURES: Cardiovascular risk factors, carotid artery intima-media thickness, and brachial artery flow mediated vasodilatation, assessed at age 24-39 years. RESULTS: After adjustment for age and adult SEP, systolic pressure was 2.3 mm Hg higher (p = 0.0002), high density lipoprotein (HDL) cholesterol 0.03 mmol/l lower (p = 0.02), and insulin resistance score (homeostasis model assessment index) 0.12 units greater (p = 0.05) among men; and systolic pressure was 1.3 mm Hg higher (p = 0.02), diastolic pressure 1.1 mm Hg higher (p = 0.01), and height 1.1 cm lower (p < 0.0001) among women for each step down the childhood SEP hierarchy. Lower childhood SEP was associated with a 20% increase in the odds of having a waist circumference > 102 cm in men and > 88 cm in women (overall p = 0.05). Childhood SEP was not associated with intima-media thickness, flow mediated vasodilatation, the metabolic syndrome, low density lipoprotein cholesterol, triglycerides, body mass index, alcohol consumption, or smoking. CONCLUSIONS: Among adults under 40, low childhood SEP predicted higher blood pressure and central obesity and, among men, unfavourable HDL cholesterol and insulin resistance, independent of current SEP. No independent effects were found on adult vascular structure, vascular function, or health related behaviours at this life stage.