Role of genetic and environmental influences on heart rate variability in middle-aged men

Our aim was to estimate causal relationships of genetic factors and different specific environmental factors in determination of the level of cardiac autonomic modulation, i.e., heart rate variability (HRV), in healthy male twins and male twins with chronic diseases. The subjects were 208 monozygotic (MZ, 104 healthy) and 296 dizygotic (DZ, 173 healthy) male twins. A structured interview was used to obtain data on lifetime exposures of occupational loading, regularly performed leisure-time sport activities, coffee consumption, smoking history, and chronic diseases from 12 yr of age through the present. A 5-min ECG at supine rest was recorded for the HRV analyses. In univariate statistical analyses based on genetic models with additive genetic, dominance genetic, and unique environmental effects, genetic effects accounted for 31-57% of HRV variance. In multivariate statistical analysis, body mass index, percent body fat, coffee consumption, smoking, medication, and chronic diseases were associated with different HRV variables, accounting for 1-11% of their variance. Occupational physical loading and leisure-time sport activities did not account for variation in any HRV variable. However, in the subgroup analysis of healthy and diseased twins, occupational loading explained 4% of the variability in heart periods. Otherwise, the interaction between health status and genetic effects was significant for only two HRV variables. In conclusion, genetic factors accounted for a major portion of the interindividual differences in HRV, with no remarkable effect of health status. No single behavioral determinant appeared to have a major influence on HRV. The effects of medication and diseases may mask the minimal effect of occupational loading on HRV.     

Socioeconomic conditions in childhood and ischaemic heart disease during middle age.

OBJECTIVE--To examine the association between socioeconomic conditions in childhood and ischaemic heart disease in middle aged men, including the role of physiological and behavioural risk factors. DESIGN--Prevalence study with extensive examination and testing and with recall of childhood conditions. SETTING--Population based study in Kuopio, Finland. SUBJECTS--Representative sample of 2679 men aged 42, 48, 54, and 60. MAIN OUTCOME MEASURES--Ischaemic findings on progressive maximal exercise test. RESULTS--Low socioeconomic style in childhood was associated with significantly higher prevalence of findings indicating ischaemias. Compared with those in the highest tertile of childhood socioeconomic conditions, the age adjusted odds ratio for subjects in the lowest tertile was 1.44 and for those in the middle tertile 1.35. Adjustment for years of cigarette smoking times the average number of cigarettes smoked, ratio of high density lipoprotein to low density lipoprotein cholesterol, fibrinogen and serum selenium concentrations, and adult height did not appreciably weaken the association. Adjustment for adult socioeconomic state resulted in a 16% decline in the association. The association was reduced to non-significance by adjustment for measures of prevalent cardiovascular illness. CONCLUSIONS--Socioeconomic state in childhood was significantly associated with ischaemic heart disease in middle aged men. Levels of risk factors measured at middle age did not account for this association, nor did adult height. Because childhood socioeconomic conditions precede the development of ischaemic heart disease the substantial impact of prevalent illness on the observed association suggests that ischaemic heart disease develops earlier in those with lower socioeconomic state during childhood.     

The genetic contribution to heart rate and heart rate variability in quiescent mice

Recent studies have suggested a genetic component to heart rate (HR) and HR variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Electrocardiogram data were recorded from 30 strains of inbred mice and 29 RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low-frequency (LF) and high-frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genomewide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated HR 1 (Hr1)]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated HRV-high-frequency 1 (Hrvhf1)] and three suggestive QTLs on chromosomes 2, 11 and 15. In conclusion, the results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. A lack of correlation between HR and HRV phenotypes in some inbred strains suggests that different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest.     

Insight into genetic determinants of resting heart rate

Background

Recent studies suggested that resting heart rate (RHR) might be an independent predictor of cardiovascular mortality and morbidity. Nonetheless, the interrelation between RHR and cardiovascular diseases is not clear. In order to resolve this puzzle, the importance of genetic determinants of RHR has been recently suggested, but it needs to be further investigated.

Objective

The aim of this study was to estimate the contribution of common genetic variations on RHR using Genome Wide Association Study.

Methods

We performed a Genome Wide Association Study in an isolated population cohort of 1737 individuals, the Italian Network on Genetic Isolates — Friuli Venezia Giulia (INGI-FVG). Moreover, a haplotype analysis was performed. A regression tree analysis was run to highlight the effect of each haplotype combination on the phenotype.

Results

A significant level of association (p < 5 × 10^− 8) was detected for Single Nucleotide Polymorphisms (SNPs) in two genes expressed in the heart: MAML1 and CANX. Founding that the three different variants of the haplotype, which encompass both genes, yielded a phenotypic correlation. Indeed, a haplotype in homozygosity is significantly associated with the lower quartile of RHR (RHR ≤ 58 bpm). Moreover no significant association was found between cardiovascular risk factors and the different haplotype combinations.

Conclusion

Mastermind-like 1 and Calnexin were found to be associated with RHR. We demonstrated a relation between a haplotype and the lower quartile of RHR in our populations. Our findings highlight that genetic determinants of RHR may be implicated in determining cardiovascular diseases and could allow a better risk stratification.     

Genetic and environmental influences on individual differences in cortisol level and circadian rhythm in middle childhood

Individuals differ widely in cortisol output over the day, but the etiology of these individual differences remains poorly understood. Twin studies are useful for quantifying genetic and environmental influences on the variation in cortisol output, lending insight into underlying influences on the components of Hypothalamic-Pituitary-Adrenal (HPA) axis functioning. Salivary cortisol was assayed on 446 twin pairs (157 monozygotic, 289 dizygotic; ages 7-8). Parents helped youth collect saliva 30 min after waking, mid-afternoon, and 30 min prior to bedtime across 3 consecutive days. We used hierarchical linear modeling to extract predicted cortisol levels and to distinguish cortisol's diurnal rhythm using a slopes-as-outcome piecewise growth curve model; two slopes captured the morning-to-afternoon and afternoon-to-evening rhythm, respectively. Separate genetic models were then fit to cortisol level at waking, mid-afternoon, and evening as well as the diurnal rhythm across morning-to-afternoon and afternoon-to-evening hours. Three results from these analyses are striking. First, morning-to-afternoon cortisol level showed the highest additive genetic variance (heritability), consistent with prior research. Second, cortisol's diurnal rhythm had an additive genetic component, particularly across the morning-to-afternoon hours. In contrast, additive genetic variation did not significantly contribute to variation in afternoon-to-evening slope. Third, the majority of variance in cortisol concentration was associated with shared family environments. In summary, both genetic and environmental factors influence cortisol's circadian rhythm, and they do so differentially across the day.     

Correlation of heredity and environmental factors in the etiology of Vilyui encephalomyelitis. II. A population genetic study in districts of Vilyui encephalomyelitis distribution]

Population-genetic investigation was carried out in the regions endemic for Viljuisk encephalomyelitis (VE). The following indices were estimated: the relationship coefficient, the inbreeding coefficient, the intensity of migration, genetic structure of the population. The aim of the investigation was to explain causes of intrapopulational and, in some cases, of intragenus accumulation of the VE patients. No evidence of isolation or increased inbreeding were found in highly affected populations. The genetic structure of a group of VE patients tested for 9 polymorphic systems did not reveal any deviation from the control group. Several VE cases in healthy populations occured in some years after the immigration of a VE patient. These data confirm the hypothesis that VE is transmitted from a VE patient to healthy persons. Among these persons fall ill those who have a hereditary determined increased sensitivity to VE which results in intrapopulation and intragenus accumulation of VE cases.