Inheritance of heart structure and physical exercise capacity: a study of left ventricular structure and exercise capacity in 7-year-old twins

The maximal aerobic power of endurance athletes is high and their heart is characterized by a larger left ventricular internal dimension than in non-athletes, and a proportional increase of wall thickness; these traits may be inherited and/or the consequence of intense physical training. To assess the influence of inheritance on physical exercise capacity and on echocardiographically determined cardiac structure, and to limit the effect of environmental factors as much as possible, we studied 15 monozygotic and 19 dizygotic 6- to 8-year-old twin pairs. Exercise capacity was expressed as the times at which the heart rates of, respectively, 150 and 170 beats min-1 were reached during a progressive exercise test on the treadmill. For these exercise times the within-pair variance was significantly larger in dizygotic compared with monozygotic twins. Therefore significant genetic variance was inferred, both when the exercise times were expressed as absolute values and after adjustment for body weight and gender. As for cardiac structure at rest, the results did not suggest a significant influence of genetic endowment on left ventricular internal diameter or on wall thickness; genetic variance was significant, however, for calculated left ventricular mass (P less than 0.05) and left ventricular mass adjusted for body weight and gender. The results are compatible with the notion that the high aerobic power of endurance athletes is at least partly inherited. Left ventricular internal dimension and wall thickness, which distinguish an athlete's heart at rest from the heart of a non-athlete, do not show a significant genetic component, suggesting that the qualities characteristic of an athlete's heart, at least as assessed at rest, are not inherited. The inheritance of aerobic power may be due to inheritance of non-cardiac factors or to cardiac features which are only expressed during exercise.     

Partitioning heritability analyses unveil the genetic architecture of human brain multidimensional functional connectivity patterns

Resting‐state functional connectivity profiles have been increasingly shown to be important endophenotypes that are tightly linked to human cognitive functions and psychiatric diseases, yet the genetic architecture of this multidimensional trait is barely understood. Using a unique sample of 1,704 unrelated, young and healthy Chinese Han individuals, we revealed a significant heritability of functional connectivity patterns in the whole brain and several subnetworks. We further proposed a partitioned heritability analysis for multidimensional functional connectivity patterns, which revealed the common and unique enrichment patterns of the genetic contributions to brain connectivity patterns for several gene sets linked to brain functions, including the genes expressed preferentially in the central nervous system and those associated with intelligence, educational attainment, attention‐deficit/hyperactivity disorder, and schizophrenia. These results for the first time reveal the genetic architecture of multidimensional brain connectivity patterns across different networks and advance our understanding of the complex relationship between gene sets, neural networks, and behaviors.     

Half of the Variation in Susceptibility to Mortality Is Genetic: Findings from Swedish Twin Survival Data

Molecular epidemiological studies confirm tremendous variability in genetic and environmental susceptibility to disease and death for humans. This variability as well as the roles of genetic and environmental factors in susceptibility to death can be estimated in the analysis of survival data on related individuals (e.g., twins). In this paper, correlated gamma-frailty models are applied to survival data on Swedish twins to estimate genetic parameters in six models of susceptibility. It is shown that the frailty model with additive genetic and nonshared environmental components fits the data best. The estimate of narrow-sense heritability in gamma frailty is about 50%. The results of genetic analysis confirm our earlier findings from the studies of Danish twins that about 50% of individual susceptibility approximated by gamma-distributed frailty is heritable.     

Genetic determination of biological age in the Mennonites of the Midwestern United States

Numerous studies have shown that longevity is moderately heritable in human populations. Longevity, however, contains limited information on functional status, since individuals may exhibit differential survival patterns. In this study, we employed a stepwise multiple regression approach to estimate biological aging in a Mennonite population, using chronological age as a dependent variable and various predictors of chronological age including subphenotypes related to diabetes, coronary heart disease, hypertension, renal function, and markers of functional ability. The residual (the difference between chronological and predicted ages) is considered a marker of biological age. In fact, two different data sets were used to obtain residuals due to the availability of data. In each analysis, chronological age was regressed on predictor variables in a stepwise manner, retaining the variables significant at the 5% level. The first analysis (N=729) included 6 significant predictors (R(2)=44.3%): glucose, blood urea nitrogen (BUN), cholesterol, albumin, systolic blood pressure (SBP), and ln potassium, and the second analysis (N=232) included 9 significant predictors (R(2)=71.5%): BUN, albumin, SBP, low-density lipoprotein cholesterol, forced expiratory volume in 1 sec (FEV1), grip strength, trunk flexibility, reaction time, and FEV1xsex. Using a variance components approach, we found that the data set-specific residuals were significantly heritable (h(2)+/-SE): first analysis=0.265+/-0.106, and second analysis=0.469+/-0.180. The residuals from the second data set appear to be more informative for biological aging, perhaps due to the inclusion of functional ability-related phenotypes in addition to the blood chemistry variables. In summary, we have shown that markers of biological aging in Mennonites are under substantial additive genetic influences.     

Genetics of monoamine metabolites in baboons: overlapping sets of genes influence levels of 5-hydroxyindolacetic acid, 3-hydroxy-4-methoxyphenylglycol, and homovanillic acid

Background

Monoamine neurotransmitters (serotonin, dopamine, and norepinephrine) are associated with several psychiatric disorders. Limited evidence suggests that monoamine levels are heritable, but no information concerning genetic relationships among monoamines is available. Further genetic analysis can help explain phenotypic correlations among monoamine levels and might eventually help identify genes involved in response to therapy or risk of psychopathology.

Methods

Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-hydroxy-4-methoxyphenylglycol (MHPG) were measured in cerebrospinal fluid from 271 baboons (Papio hamadryas). Variance components methods were used to estimate heritabilities, and multivariate analyses were used to estimate genetic correlations (pleiotropy) and environmental correlations between metabolites.

Results

Each metabolite exhibited significant heritability in baboons (5-HIAA: h² = .30 ± .17; MHPG: h² = .36 ± .16; HVA: h² = .50 ± .19). Multivariate analyses revealed genetic correlations between 5-HIAA and HVA and between HVA and MHPG. Environmental correlations were found between 5-HIAA and HVA and between 5-HIAA and MHPG.

Conclusions

Overlapping, nonidentical sets of genes influence individual variation in 5-HIAA, MHPG, and HVA levels among baboons. The phenotypic correlation between 5-HIAA and HVA observed in nonhuman primates and humans is likely due to both shared genetic and environmental factors. Genetic analyses of monoamine levels in primates can provide novel information concerning the genetics of variation among humans.     

Kenneth George Eldridge

Genetic parameters, including heritabilities, trait-trait correlations and across-site correlations for growth traits and quambalaria shoot blight damage were estimated in four Corymbia citriodora subsp. variegata clonal trials in northern New South Wales, Australia. Additive and non-additive variances were calculated separately to allow the estimation of broad—and narrow-sense heritabilities.

Quambalaria shoot blight damage at ages 1 and 3.5 y was under predominantly non-additive genetic control (H² = 0.02–0.46, h² = 0–0.17). Growth traits at age 5 y were under moderate genetic control (H² = 0.32–0.54, h² = 0–0.54). Growth traits were strongly correlated with quambalaria shoot blight damage. Across-site correlations were low for quambalaria shoot blight damage (r_g = 0.13–1.00) but high (>0.8) for the growth traits. Index selection was used to determine the most efficient selection strategies for improvement of growth and disease tolerance.     

Increased heritability for lower IQ levels?

Dettermanet al. (1990) presented evidence based on twins that the heritability of IQ may be higher in the lower part of the IQ range. We first offer an alternative test for differential heritability across the IQ range, based on the analysis of absolute intrapair differences of monozygotic versus dizygotic twins. We then review two previous studies, each containing more twins than the sample of Dettermanea al., which examined the distribution of intrapair absolute differences. In contrast to the study of Dettermanet al., both yielded results more compatible with higher heritability in the upper range of IQ. We discuss various interpretations of these findings and show how our proposed test might aid in distinguishing among them.     

婴幼儿哮喘与支气管哮喘的遗传相关性研究

目的 探讨婴幼儿哮喘及支气管哮喘的遗传方式, 观察两者的遗传相关性, 为哮喘的三级预防提供理论依据。方法 通过Falconer回归法估计婴幼儿哮喘与支气管哮喘的遗传度, Logistic回归分析总结两者的主要危险因素, S-N-K法方差分析进行比较。结果 婴幼儿哮喘的遗传度为(80.53±7.85)%, 支气管哮喘的遗传度为(78.87±6.99)%, 两者危险因素比较无统计学意义(P>0.05)。结论 遗传因素在哮喘的发生、发展中起主要作用, 其他危险因素起协同作用, 两者具有密切相关性。因此预防婴幼儿哮喘, 可以有效的减少和预防支气管哮喘的发生。     

Twin study of genetic and environmental effects on lipid levels

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.     

Lifestyle factors in monozygotic and dizygotic twins

In examining genetic influences on biological variables using twins, it may be important to examine the distribution between and within twin pairs of demographic and lifestyle factors that may themselves affect the biological variable being studied. We explored the distribution of demographic and lifestyle factors that may affect blood lipid levels or ischaemic heart disease (IHD) risk among a sample of 106 monozygotic (MZ) and 94 like-sex dizygotic (DZ) twin pairs. In our sample, MZ twins were statistically significantly different from DZ twins only in marital status, cigarette smoking habits, and the ratio of polyunsaturated to saturated fat (P:S ratio) in their dietary intake. The latter variable was among many dietary variables examined (using 4-day weighed food diaries), and the size of the difference in intake was small. When comparisons were made of the similarities within twin pairs, we found members of MZ twin pairs to be statistically significantly closer than DZ twins in educational achievement, occupation, cigarette smoking, and exercise habits, and the number of days a week on which alcohol was consumed. These last three variables were consistently closer among twins with closer contact than among those with a smaller degree of current shared environment. For 12 of the 13 nutrients examined, the within-pair correlations were higher for MZ than for DZ twins, although our test for significant genetic variance showed statistical significance only for intake of complex carbohydrates. We conclude that MZ twins share demographic and lifestyle factors that might influence the risk of IHD and blood lipid levels to a greater degree than do DZ twins, although it is difficult to say if these similarities in lifestyle result from genetic influences or not. Nevertheless, ascribing differences between correlations in MZ and DZ twin pairs for lipid levels as being purely "genetic"--as implicit in conventional measures of heritability--is likely to overestimate the influence of genetic factors.