A Longitudinal Multilevel Study of the “Social” Genotype and Diversity of the Phenotype

Sociability and social domain-related behaviors have been associated with better well-being and endogenous oxytocin levels. Inspection of the literature, however, reveals that the effects between sociability and health outcomes, or between sociability and genotype, are often weak or inconsistent. In the field of personality psychology, the social phenotype is often measured by error-prone assessments based on different theoretical frameworks, which can partly explain the inconsistency of the previous findings. In this study, we evaluated the generalizability of “sociability” measures by partitioning the population variance in adulthood sociability using five indicators from three personality inventories and assessed in two to four follow-ups over a 15-year period (n = 1,573 participants, 28,323 person-observations; age range 20–50 years). Furthermore, we tested whether this variance partition would shed more light to the inconsistencies surrounding the “social” genotype, by using four genetic variants (rs1042778, rs2254298, rs53576, rs3796863) previously associated with a wide range of human social functions. Based on our results, trait (between-individual) variance explained 23% of the variance in overall sociability, differences between sociability indicators explained 41%, state (within-individual) variance explained 5% and measurement errors explained 32%. The genotype was associated only with the sociability indicator variance, suggesting it has specific effects on sentimentality and emotional sharing instead of reflecting general sociability

Pravastatin-induced improvement in coronary reactivity and circulating ATP and ADP levels in young adults with type 1 diabetes

Aims: Extracellular ATP and ADP regulate diverse inflammatory, prothrombotic and vasoactive responses in the vasculature. Statins have been shown to modulate their signaling pathways in vitro. We hypothesized that altered intravascular nucleotide turnover modulates vasodilation in patients with type 1 diabetes (T1DM), and this can be partly restored with pravastatin therapy. Methods: In this randomized double blind study, plasma ATP and ADP levels and echocardiography-derived coronary flow velocity response to cold pressor test (CPT) were concurrently assessed in 42 normocholesterolemic patients with T1DM (age 30 +/- 6 years, LDL cholesterol 2.5 +/- 0.6 mmol/L) before and after four-month treatment with pravastatin 40 mg/day or placebo (n = 22 and n = 20, respectively), and in 41 healthy control subjects. Results: Compared to controls, T1DM patients had significantly higher concentrations of ATP (p <0.01) and ADP (p <0.01) and these levels were partly restored after treatment with pravastatin (p = 0.002 and p = 0.007, respectively), but not after placebo (p = 0.06 and p = 0.14, respectively). Coronary flow velocity acceleration was significantly lower in T1DM patients compared to control subjects, and it increased from pre- to post-intervention in the pravastatin (p = 0.02), but not in placebo group (p = 0.15). Conclusions: Pravastatin treatment significantly reduces circulating ATP and ADP levels of T1DM patients, and concurrently improves coronary flow response to CPT. This study provides a novel insight in purinergic mechanisms involved in pleiotropic effects of pravastatin.Peer reviewe

Associations of parental physical activity trajectories with offspring's physical activity patterns from childhood to middle adulthood : The Young Finns Study

Peer reviewe

Associations Between Early Childcare Environment and Different Aspects of Adulthood Sociability: The 32-Year Prospective Young Finns Study

Sociability is a widely studied trait that has been linked both with individual well-and ill-being. Although early childcare has been shown to affect social competence in children, its role in the development of different aspects of adulthood sociability is poorly understood. Using a longitudinal population-based sample (N = 464), this study investigated whether childcare arrangements at ages 3 or 6 are associated with self-reported adulthood sociability at ages 20 to 35 years. A total of five aspects of sociability were measured using three well-established personality inventories (EAS, NEO-FFI, and TCI). Multilevel modeling was applied to examine the association between early care and adulthood sociability, adjusting for several sources of random variation (between-individual variance, within-individual variance between measurement times, variance between used sociability indicators, and error variance that cannot be attributed to the previously mentioned) and potential confounders (disruptive behavior in childhood, parental socio-economic status, parent-child relationship quality, maternal age, and the number of children in the family). Based on our results, in comparison to home care, family daycare and center-based daycare at age 3 and center-based daycare at age 6 were associated with higher sociability later in life. The association was strongest for aspects of sociability that emphasize the willingness to be surrounded by other people and to be attached to them. In other words, characteristics of early care may contribute uniquely to the development of these aspects of sociability with effects that persist into adult life

Associations Between Early Childcare Environment and Different Aspects of Adulthood Sociability : The 32-Year Prospective Young Finns Study

Sociability is a widely studied trait that has been linked both with individual well-and ill-being. Although early childcare has been shown to affect social competence in children, its role in the development of different aspects of adulthood sociability is poorly understood. Using a longitudinal population-based sample (N = 464), this study investigated whether childcare arrangements at ages 3 or 6 are associated with self-reported adulthood sociability at ages 20 to 35 years. A total of five aspects of sociability were measured using three well-established personality inventories (EAS, NEO-FFI, and TCI). Multilevel modeling was applied to examine the association between early care and adulthood sociability, adjusting for several sources of random variation (between-individual variance, within-individual variance between measurement times, variance between used sociability indicators, and error variance that cannot be attributed to the previously mentioned) and potential confounders (disruptive behavior in childhood, parental socio-economic status, parent-child relationship quality, maternal age, and the number of children in the family). Based on our results, in comparison to home care, family daycare and center-based daycare at age 3 and center-based daycare at age 6 were associated with higher sociability later in life. The association was strongest for aspects of sociability that emphasize the willingness to be surrounded by other people and to be attached to them. In other words, characteristics of early care may contribute uniquely to the development of these aspects of sociability with effects that persist into adult lifePeer reviewe

Associations of parental physical activity trajectories with offspring's physical activity patterns from childhood to middle adulthood: The Young Finns Study

We investigated the association of parental physical activity (PA) trajectories with offspring's youth and adult PA. Self-reported PA data were extracted from the Young Finns Study with three follow-ups for parents between 1980 and 1986 and nine follow-ups for their offspring in youth between 1980 and 2011 (aged 9-39 years, n = 2402) and in adulthood in 2018. Accelerometer-derived PA was quantified in 2018-2020 (aged 43-58 years, n = 1134). Data were analyzed using mixture models and conducted in 2022. We identified three trajectories for fathers and mothers (high-stable activity, 20.2%/16.6%; moderate-stable activity, 50.5%/49.6%; and low-stable activity, 29.4%/33.7%) and four for youth male and female offspring (persistently active, 13.4%/5.1%; increasingly active, 32.1%/43.1%; decreasingly active, 14.4%/12.6%; and persistently low-active, 40.1%/39.1%). Compared to low-stable active parents, high-stable active fathers had a higher probability of having their sons and daughters classified as persistently active, increasingly active, and decreasingly active in youth (Brange = 0.50-1.79, all p range = 0.63-1.16, all p < 0.009). Fathers' and mothers' high-stable activity was associated with higher self-reported PA of adult offspring than parental low-stable activity. Persistently active and increasingly active offspring in youth accumulated more adult total PA, moderate-to-vigorous PA, step counts, and self-reported PA than persistently low-active ones (all p < 0.036). Parental persistent PA, particularly paternal persistent PA, predicts offspring's PA concurrently and prospectively. Increasing and maintaining PA in youth predicts higher PA levels in midlife

Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality

Aims The purpose of this study was to identify novel genetic variants influencing circulating asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and to evaluate whether they have a prognostic value on cardiovascular mortality. Methods and results We conducted a genome-wide association study on the methylarginine traits and investigated the predictive value of the new discovered variants on mortality. Our meta-analyses replicated the previously known locus for ADMA levels in DDAH1 (rs997251; P = 1.4 × 10−40), identified two non-synomyous polymorphisms for SDMA levels in AGXT2 (rs37369; P = 1.4 × 10−40 and rs16899974; P = 1.5 × 10−38) and one in SLC25A45 (rs34400381; P = 2.5 × 10−10). We also fine-mapped the AGXT2 locus for further independent association signals. The two non-synonymous AGXT2 variants independently associated with SDMA levels were also significantly related with short-term heart rate variability (HRV) indices in young adults. The major allele (C) of the novel non-synonymous rs16899974 (V498L) variant associated with decreased SDMA levels and an increase in the ratio between the low- and high-frequency spectral components of HRV (P = 0.00047). Furthermore, the SDMA decreasing allele (G) of the non-synomyous SLC25A45 (R285C) variant was associated with a lower resting mean heart rate during the HRV measurements (P = 0.0046), but not with the HRV indices. None of the studied genome-wide significant variants had any major effect on cardiovascular or total mortality in patients referred for coronary angiography. Conclusions AGXT2 has an important role in SDMA metabolism in humans. AGXT2 may additionally have an unanticipated role in the autonomic nervous system regulation of cardiac functio

Effects of cognac on coronary flow reserve and plasma antioxidant status in healthy young men

<p>Abstract</p> <p>Background</p> <p>The cardioprotective effects of certain alcoholic beverages are partly related to their polyphenol content, which may improve the vasodilatory reactivity of arteries. Effect of cognac on coronary circulation, however, remains unknown. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of cognac improve coronary reactivity as assessed with cold pressor testing (CPT) and coronary flow reserve (CFR) measument.</p> <p>Methods</p> <p>Study group consisted of 23 subjects. Coronary flow velocity and epicardial diameter was assessed using transthoracic echocardiography at rest, during CPT and adenosine infusion-derived CFR measurements before drinking, after a moderate (1.2 ± 0.1 dl) and an escalating high dose (total amount 2.4 ± 0.3 dl) of cognac. To explore the bioavailability of antioxidants, the antioxidant contents of cognac was measured and the absorption from the digestive tract was verified by plasma antioxidant capacity determination.</p> <p>Results</p> <p>Serum alcohol levels increased to 1.2 ± 0.2‰ and plasma antioxidant capacity from 301 ± 43.9 μmol/l to 320 ± 25.0 μmol/l by 7.6 ± 11.8%, (p = 0.01) after high doses of cognac. There was no significant change in flow velocity during CPT after cognac ingestion compared to control day. CFR was 4.4 ± 0.8, 4.1 ± 0.9 (p = NS), and 4.5 ± 1.2 (p = NS) before drinking and after moderate and high doses on cognac day, and 4.5 ± 1.4, and 4.0 ± 1.2 (p = NS) on control day.</p> <p>Conclusion</p> <p>Cognac increased plasma antioxidant capacity, but it had no effect on coronary circulation in healthy young men.</p> <p>Trial Registration</p> <p>NCT00330213</p

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.