Sex differences in genetic and environmental factors contributing to body-height.

Sex differences in the heritability of self-reported body-height in two Finnish twin cohorts were studied by using sex-limitation models. The first cohort was born in 1938-1949 (N = 4873 twin pairs) and the second in 1975-1979 (N = 2374 twin pairs). Body-height was greater in the younger cohort (difference of 3.1 cm for men and 2.9 cm for women). The heritability estimates were higher among men (h2 = 0.87 in the older cohort and h2 = 0.82 in the younger cohort) than women (h2 = 0.78 and h2 = 0.67, respectively). Sex-specific genetic factors were not statistically significant in either cohort, suggesting that the same genes contribute to variation in body height for both men and women. The stronger contribution of environmental factors to body-height among women questions the hypothesis that women are better buffered against environmental stress, at least for this phenotype.     

Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries.

Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20-29 and 30-39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.     

Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings

The study of continuously varying, quantitative traits is important in evolutionary biology, agriculture, and medicine. Variation in such traits is attributable to many, possibly interacting, genes whose expression may be sensitive to the environment, which makes their dissection into underlying causative factors difficult. An important population parameter for quantitative traits is heritability, the proportion of total variance that is due to genetic factors. Response to artificial and natural selection and the degree of resemblance between relatives are all a function of this parameter. Following the classic paper by R. A. Fisher in 1918, the estimation of additive and dominance genetic variance and heritability in populations is based upon the expected proportion of genes shared between different types of relatives, and explicit, often controversial and untestable models of genetic and non-genetic causes of family resemblance. With genome-wide coverage of genetic markers it is now possible to estimate such parameters solely within families using the actual degree of identity-by-descent sharing between relatives. Using genome scans on 4,401 quasi-independent sib pairs of which 3,375 pairs had phenotypes, we estimated the heritability of height from empirical genome-wide identity-by-descent sharing, which varied from 0.374 to 0.617 (mean 0.498, standard deviation 0.036). The variance in identity-by-descent sharing per chromosome and per genome was consistent with theory. The maximum likelihood estimate of the heritability for height was 0.80 with no evidence for non-genetic causes of sib resemblance, consistent with results from independent twin and family studies but using an entirely separate source of information. Our application shows that it is feasible to estimate genetic variance solely from within-family segregation and provides an independent validation of previously untestable assumptions. Given sufficient data, our new paradigm will allow the estimation of genetic variation for disease susceptibility and quantitative traits that is free from confounding with non-genetic factors and will allow partitioning of genetic variation into additive and non-additive components.     

The quantitative genetics of incipient speciation: heritability and genetic correlations of skeletal traits in populations of diverging Favia fragum ecomorphs

Recent speciation events provide potential opportunities to understand the microevolution of reproductive isolation. We used a marker-based approach and a common garden to estimate the additive genetic variation in skeletal traits in a system of two ecomorphs within the coral species Favia fragum: a Tall ecomorph that is a seagrass specialist, and a Short ecomorph that is most abundant on coral reefs. Considering both ecomorphs, we found significant narrow-sense heritability (h(2) ) in a suite of measurements that define corallite architecture, and could partition additive and nonadditive variation for some traits. We found positive genetic correlations for homologous height and length measurements among different types of vertical plates (costosepta) within corallites, but negative correlations between height and length within, as well as between costosepta. Within ecomorphs, h(2) estimates were generally lower, compared to the combined ecomorph analysis. Marker-based estimates of h(2) were comparable to broad-sense heritability (H) obtained from parent-offspring regressions in a common garden for most traits, and similar genetic co-variance matrices for common garden and wild populations may indicate relatively small G × E interactions. The patterns of additive genetic variation in this system invite hypotheses of divergent selection or genetic drift as potential evolutionary drivers of reproductive isolation.     

Sex difference in heritability of BMI in South Korean adolescent twins

Twin studies of BMI on the basis of Asian twins are extremely rare. Eight hundred eighty-eight pairs of twins [279 monozygotic (MZ) and 82 dizygotic (DZ) pairs of male twins, 319 MZ and 82 DZ pairs of female twins, and 126 opposite-sex pairs of DZ twins] completed items concerning height and weight through a mail and a telephone survey. A general sex-limitation model was applied to the data. Heritability estimate was greater among women than among men. However, there was little evidence of sex-specific genes. Under the best-fitting model, additive genetic variances were 82% [95% confidence interval (CI): 72% to 95%] for men and 87% (95% CI: 77% to 99%) for women; shared environmental variances were negligible in both men and women. These estimates of genetic and environmental factors in BMI found among South Korean adolescent twins were broadly in the range of those reported in previous studies of BMI based on Western twin samples.     

The validity and heritability of self-report osteoarthritis in an Australian older twin sample.

In order to investigate the genetic and environmental antecedents of osteoarthritis (OA), self-report measures of joint pain, stiffness and swelling were obtained from a population-based sample of 1242 twin pairs over 50 years of age. In order to provide validation for these self-report measures, a subsample of 118 twin pairs were examined according to the American College of Rheumatology clinical and radiographic criteria for the classification of osteoarthritis. A variety of statistical methods were employed to identify the model derived from self-report variables which would provide optimal prediction of these standardised assessments, and structural equation modelling was used to determine the relative influences of genetic and environmental influences on the development of osteoarthritis. Significant genetic effects were found to contribute to osteoarthritis of the hands, hips and knees in women, with heritability estimates ranging from 30-46% depending on the site. In addition, the additive genetic effects contributing to osteoarthritis in various parts of the body were confirmed to be the same. Statistically significant familial aggregation of osteoarthritis in men was also observed, but it was not possible to determine whether this was due to genetic or shared environmental effects.     

Variation in heritability of tadpole growth: an experimental analysis

Heritability characteristically shows large variation between traits, among populations and species, and through time. One of the reasons for this is its dependence on gene frequencies and how these are altered by selection and drift through the evolutionary process. We studied variation in heritability of tadpole growth rate in populations of the Swedish common frog, Rana temporaria. In populations evolving under warmer conditions, we have demonstrated elsewhere that tadpoles show better growth and physiological performance at relatively higher temperatures than tadpoles with an evolutionary history in a relatively cooler part of the distribution range. In the current study, we ask whether this process of divergence under natural selection has influenced the genetic architecture as visualised in estimates of heritability of growth rate at different temperature treatments under laboratory conditions. The results suggest that the additive genetic variance varies between treatments and is highest in a treatment that is common to both populations. Our estimates of narrow sense heritability are generally higher in the thermal regime that dominates in the natural environment. The reason for this appears not primarily to be because the component of additive genetic variation is higher in relation to the total phenotypic variation under these conditions, but because the part of the phenotypic variance explained by environmental variation increases at temperatures to which the current populations has been less frequently under selection.     

The influence of genetic and environmental factors in estimations of current body size, desired body size, and body dissatisfaction.

The objective was to investigate the genetic epidemiology of figural stimuli. Standard figural stimuli were available from 5,325 complete twin pairs: 1,751 (32.9%) were monozygotic females, 1,068 (20.1%) were dizygotic females, 752 (14.1%) were monozygotic males, 495 (9.3%) were dizygotic males, and 1,259 (23.6%) were dizygotic male-female pairs. Univariate twin analyses were used to examine the influences on the individual variation in current body size and ideal body size. These data were analysed separately for men and women in each of five age groups. A factorial analysis of variance, with polychoric correlations between twin pairs as the dependent variable, and age, sex, zygosity, and the three interaction terms (age x sex, age x zygosity, sex x zygosity) as independent variables, was used to examine trends across the whole data set. Results showed genetic influences had the largest impact on the individual variation in current body size measures, whereas non-shared environmental influences were associated with the majority of individual variation in ideal body size. There was a significant main effect of zygosity (heritability) in predicting polychoric correlations for current body size and body dissatisfaction. There was a significant main effect of gender and zygosity in predicting ideal body size, with a gender x zygosity interaction. In common with BMI, heritability is important in influencing the estimation of current body size. Selection of desired body size for both men and women is more strongly influenced by environmental factors.     

Genetic study of the height and weight process during infancy.

Longitudinal height and weight data from 4649 Dutch twin pairs between birth and 2.5 years of age were analyzed. The data were first summarized into parameters of a polynomial of degree 4 by a mixed-effects procedure. Next, the variation and covariation in the parameters of the growth curve (size at one year of age, growth velocity, deceleration of growth, rate of change in deceleration [i.e., jerk] and rate of change in jerk [i.e., snap]) were decomposed into genetic and nongenetic sources. Additionally, the variation in the estimated size at birth and at 2 years of age interpolated from the polynomial was decomposed into genetic and nongenetic components. Variation in growth was best characterized by a genetic model which included additive genetic, common environmental and specific environmental influences, plus effects of gestational age. The effect of gestational age was largest for size at birth, explaining 39% of the variance. The differences between monozygotic and dizygotic twin correlations were largest for size at 1 and 2 years of age and growth velocity of weight, which suggests that these parameters are more influenced by heritability than size at birth, deceleration and jerk. The percentage of variance explained by additive genetic influences for height at 2 years of age was 52% for females and 58% for males. For weight at 2 years of age, heritability was approximately 58% for both sexes. Variation in snap height for males was also mainly influenced by additive genetic factors, while snap for females was influenced by both additive genetic and common environmental factors. The correlations for the additive genetic and common environmental factors for deceleration and snap are large, indicating that these parameters are almost entirely under control of the same additive genetic and common environmental factors. Female jerk and snap, and also female height at birth and height at 2 years of age, are mostly under control of the same additive genetic factor.     

Assumptions and Properties of Limiting Pathway Models for Analysis of Epistasis in Complex Traits

For most complex traits, results from genome-wide association studies show that the proportion of the phenotypic variance attributable to the additive effects of individual SNPs, that is, the heritability explained by the SNPs, is substantially less than the estimate of heritability obtained by standard methods using correlations between relatives. This difference has been called the “missing heritability”. One explanation is that heritability estimates from family (including twin) studies are biased upwards. Zuk et al. revisited overestimation of narrow sense heritability from twin studies as a result of confounding with non-additive genetic variance. They propose a limiting pathway (LP) model that generates significant epistatic variation and its simple parametrization provides a convenient way to explore implications of epistasis. They conclude that over-estimation of narrow sense heritability from family data (‘phantom heritability’) may explain an important proportion of missing heritability. We show that for highly heritable quantitative traits large phantom heritability estimates from twin studies are possible only if a large contribution of common environment is assumed. The LP model is underpinned by strong assumptions that are unlikely to hold, including that all contributing pathways have the same mean and variance and are uncorrelated. Here, we relax the assumptions that underlie the LP model to be more biologically plausible. Together with theoretical, empirical, and pragmatic arguments we conclude that in outbred populations the contribution of additive genetic variance is likely to be much more important than the contribution of non-additive variance.     

Genome partitioning of genetic variation for height from 11,214 sibling pairs

Height has been used for more than a century as a model by which to understand quantitative genetic variation in humans. We report that the entire genome appears to contribute to its additive genetic variance. We used genotypes and phenotypes of 11,214 sibling pairs from three countries to partition additive genetic variance across the genome. Using genome scans to estimate the proportion of the genomes of each chromosome from siblings that were identical by descent, we estimated the heritability of height contributed by each of the 22 autosomes and the X chromosome. We show that additive genetic variance is spread across multiple chromosomes and that at least six chromosomes (i.e., 3, 4, 8, 15, 17, and 18) are responsible for the observed variation. Indeed, the data are not inconsistent with a uniform spread of trait loci throughout the genome. Our estimate of the variance explained by a chromosome is correlated with the number of times suggestive or significant linkage with height has been reported for that chromosome. Variance due to dominance was not significant but was difficult to assess because of the high sampling correlation between additive and dominance components. Results were consistent with the absence of any large between-chromosome epistatic effects. Notwithstanding the proposed architecture of complex traits that involves widespread gene-gene and gene-environment interactions, our results suggest that variation in height in humans can be explained by many loci distributed over all autosomes, with an additive mode of gene action.     

A population-based twin study on sleep duration and body composition

The aim of this study is to investigate the relationship between sleep duration and body composition and to estimate the genetic contribution of sleep duration and body composition in a Chinese twin population. This cross-sectional analysis included 738 men and 511 women aged 21-72 year. Anthropometric and dual-energy X-ray absorptiometry (DXA) measures of body composition were used. Sleep duration was obtained from a standard sleep questionnaire. Multiple regression models were used to examine the association between sleep duration and body composition measures. Structural equation modeling was used to assess the heritability of sleep duration and body composition. Compared with individuals in the 2nd and 3rd age-specific quartiles of sleep duration (reference group), shorter (1st quartile) sleep duration among women but not men was associated with higher z-scores (0.248-0.317) for all adiposity measures--BMI, fat mass index (FMI), percent body fat mass (%BF), and percent trunk fat mass (%TF), P < 0.05 for each--and with 0.306 lower z-scores for percent body lean mass (%LM) and 0.353 lower lean/fat mass ratio (LFR), P < 0.01 for each. The heritability of sleep duration was 0.27 in men and 0.29 in women, while the heritability of body composition was as high as 0.56-0.73 after adjustment for age in both genders. Short sleep duration was associated with increased body fat and decreased lean body mass in women but not in men. Sleep duration was largely influenced by environmental factors while adiposity measures were mainly influenced by genetic factors.     

Common genetic components of obesity traits and serum leptin

To estimate common and distinct genetic influences on a panel of obesity-related traits and serum leptin level in adults. In a cross-sectional study of 625 Danish, adult, healthy, monozygotic, and same-sex dizygotic twin pairs of both genders, we carried out detailed anthropometry (height, weight, waist and hip, and skin-fold thickness, body composition assessment by bioimpedance (fat mass and fat-free mass), and measurement of serum leptin level. Bivariate variance component analyses estimated the additive genetic correlations between these measurements. The genetic correlations between the traits for overall fatness (BMI and fat mass index, kg/m(2)) were 0.94 in men and 0.98 in women, and their correlations with the various local fatness measures ranged from 0.49 to 0.83 in men and from 0.70 to 0.87 in women. The correlations between the truncal measures (waist circumference and truncal skin folds) and between the peripheral measures (hip circumference and peripheral skin folds) were 0.57 and 0.47 in men and 0.71 and 0.70 in women, respectively. The correlations between the truncal and peripheral measures ranged between 0.49 and 0.72 in men and between 0.61 and 0.82 in women. For leptin vs. the various measures of overall and local fatness the correlations ranged from 0.54 to 0.74 in men and from 0.48 to 0.75 in women. All correlations were significantly <1.00. The study supports control of overall fat mass and peripheral and truncal fat mass by both shared and different genetic components, which suggests that it is important to distinguish between the different phenotypes in the search for genes involved in the development of obesity.     

Heritability of morphology in brook trout with variable life histories

Distinct morphological variation is often associated with variation in life histories within and among populations of both plants and animals. In this study, we examined the heritability of morphology in three hatchery strains of brook trout (Salvelinus fontinalis), which were historically or are currently used for stocking and supplementation of both migratory and resident ecotypes in the upper Great Lakes region. In a common garden experiment, significant variation in body morphology was observed within and across populations sampled at three time periods. The most notable differences among strains were differences in dorso-ventral body depth and the shape of the caudal peduncle, with some differences in the anterior-posterior placement of the dorsal and ventral fins. Variation with and among 70 half-sib families indicates that heritabilities of morphology and body size were significant at most developmental time points both within and across strains. Heritabilities for morphological characters within strains ranged from 0 to 0.95 across time points. Significant within-strain heritabilities for length ranged from 0 to 0.93 across time points and for weight ranged from 0 to 0.88. Significant additive genetic variation exists within and across hatchery brook trout strains for morphology and size, indicating that these traits are capable of responding to natural or artificial selection.     

Natural selection and quantitative genetics of life-history traits in Western women: a twin study

Whether contemporary human populations are still evolving as a result of natural selection has been hotly debated. For natural selection to cause evolutionary change in a trait, variation in the trait must be correlated with fitness and be genetically heritable and there must be no genetic constraints to evolution. These conditions have rarely been tested in human populations. In this study, data from a large twin cohort were used to assess whether selection will cause a change among women in a contemporary Western population for three life-history traits: age at menarche, age at first reproduction, and age at menopause. We control for temporal variation in fecundity (the "baby boom" phenomenon) and differences between women in educational background and religious affiliation. University-educated women have 35% lower fitness than those with less than seven years education, and Roman Catholic women have about 20% higher fitness than those of other religions. Although these differences were significant, education and religion only accounted for 2% and 1% of variance in fitness, respectively. Using structural equation modeling, we reveal significant genetic influences for all three life-history traits, with heritability estimates of 0.50, 0.23, and 0.45, respectively. However, strong genetic covariation with reproductive fitness could only be demonstrated for age at first reproduction, with much weaker covariation for age at menopause and no significant covariation for age at menarche. Selection may, therefore, lead to the evolution of earlier age at first reproduction in this population. We also estimate substantial heritable variation in fitness itself, with approximately 39% of the variance attributable to additive genetic effects, the remainder consisting of unique environmental effects and small effects from education and religion. We discuss mechanisms that could be maintaining such a high heritability for fitness. Most likely is that selection is now acting on different traits from which it did in pre-industrial human populations.     

Heritability of Eating Behavior Assessed Using the DEBQ (Dutch Eating Behavior Questionnaire) and Weight‐related Traits: The Healthy Twin Study

The heritability of eating behavior and body weight–related traits in Asian populations has not been reported. The purpose of this study was to estimate the heritability of eating behavior and the body weight–related traits of current weight and self‐reported past weight among twins and their families. Study subjects were 2,144 Korean, adult, same‐sex twins and their families at the ages between 20 and 65 years (443 monozygotic (MZ) and 124 dizygotic (DZ) twin pairs, and 1,010 individuals of their family). The Dutch Eating Behavior Questionnaire (DEBQ) was used to assess three eating behavior subscales measuring restraint, emotional eating, and external eating. A variance component approach was used to estimate heritability. After consideration of shared environmental effects and adjustment for age and sex effects, the heritability estimates ± s.e. among twins and their family members were 0.31 ± 0.036 for restraint, 0.25 ± 0.098 for emotional eating, 0.25 ± 0.060 for external eating, 0.77 ± 0.032 for measured current body weight, and 0.70 ± 0.051 for self‐reported weight at 20 years old. The three DEBQ subscales were associated with all weight related traits after adjustment for age and sex. These results suggest eating behaviors and weight‐related traits have a genetic influence, and eating behaviors are associated with obesity indexes. Our findings from Korean twin family were similar to those reported in Western populations.     

Sexual variation in heritability and genetic correlations of morphological traits in house sparrow (Passer domesticus)

Estimates of genetic components are important for our understanding of how individual characteristics are transferred between generations. We show that the level of heritability varies between 0.12 and 0.68 in six morphological traits in house sparrows (Passer domesticus L.) in northern Norway. Positive and negative genetic correlations were present among traits, suggesting evolutionary constraints on the evolution of some of these characters. A sexual difference in the amount of heritable genetic variation was found in tarsus length, wing length, bill depth and body condition index, with generally higher heritability in females. In addition, the structure of the genetic variance-covariance matrix for the traits differed between the sexes. Genetic correlations between males and females for the morphological traits were however large and not significantly different from one, indicating that sex-specific responses to selection will be influenced by intersexual differences in selection differentials. Despite this, some traits had heritability above 0.1 in females, even after conditioning on the additive genetic covariance between sexes and the additive genetic variances in males. Moreover, a meta-analysis indicated that higher heritability in females than in males may be common in birds. Thus, this indicates sexual differences in the genetic architecture of birds. Consequently, as in house sparrows, the evolutionary responses to selection will often be larger in females than males. Hence, our results suggest that sex-specific additive genetic variances and covariances, although ignored in most studies, should be included when making predictions of evolutionary changes from standard quantitative genetic models.     

Heritability of quantitative variation at the group-specific component (Gc) locus

Human group-specific component (Gc) is the plasma transport protein for vitamin D; in addition, polymorphic electrophoretic variants of Gc are found in all human populations. Because of its physiologic importance and in view of the extensive genetic variation at the Gc locus, we have determined the heritability of quantitative variation in Gc by comparing a series of monozygotic (MZ) and dizygotic (DZ) twins of known Gc genotype. The series included 31 MZ twin pairs, 13 DZ twin pairs, and 45 unrelated controls. Since Gc concentration is increased by estrogens, pregnant women and women taking oral contraceptives were excluded. We found no age-related differences in Gc concentration or differences between males and females, but the concentrations of Gc in the three electrophoretically determined genotypes were significantly different from each other. Using classical methods of heritability analysis, the overall heritability of variation in Gc concentration is approximately 70%. Heritability in males is greater than in females, probably reflecting the additional environmental effect of estrogens in women. To determine if the differences in Gc concentration between the three genotypes explain the high heritability, a new variance decomposition procedure was developed following classical methods in quantitative genetics. Application of this method suggests that 19% of the total variation in Gc concentration, combining both sexes, is due to electrophoretic differences between individuals (30% in females and 20% in males). Thus, the genetic component of variation in Gc concentration can be decomposed into a major gene component--the result of electrophoretic variation at the structural locus--and a second, unexplained, polygenic component.