Fourier analysis of facial profiles of young twins

Twins studies provide a powerful approach to determining the relative contribution of genetics and environment to observed variation. Such studies assume trait differences in monozygous (MZ) twins are due to environmental factors and those in dizygous (DZ) twins are due to both genetic and environmental factors. This study quantitated facial profiles of twins using Fourier equations, determining their value in profile analysis and the assessment of the genetic contribution to facial shape. Standardized profile slide photographs of 79 pairs of 4-6 year-old twins (37 MZ pairs, 42 DZ pairs) were scanned and x and y coordinates were extracted from each profile using sellion and Camper's plane as references. The coordinates were subjected to Fourier analysis and the normalised vertex projection coefficients were studied. The means of the differences between coefficients for MZ co-twins did not differ significantly from that of DZ co-twins, although the DZ group showed higher mean differences in the higher harmonics. Subjective examination of superimposed reconstructions showed wider variation between DZ co-twins than MZ co-twins. Correct classification of twins by discriminant function analysis using Fourier coefficients was similar for both groups (MZ: 70.3%; DZ: 73.8%). Fourier analysis could quantitate facial profiles of young children and differentiate some details, but was unable to discriminate between genetic and environmental influences, and any possible interactions between these influences, on their overall facial profiles at this developmental stage.     

Genetic influences on premature parturition in an Australian twin sample.

We investigated possible genetic influences on women's liability to preterm birth, using data from a large sample of Australian female twin pairs. In a 1988-90 questionnaire survey, both members of 905 parous twin pairs (579 monozygotic and 326 dizygotic) reported on whether deliveries had been more than two weeks preterm. Tetrachoric twin pair correlations for first birth were rMZ = 0.20+/-0.11 and rDZ = -0.03+/-0.14, and for any birth were rMZ = 0.30+/-0.08 and rDZ = 0.03+/-0.11. Best-fitting models to data contained only additive genetic influences and individual environmental effects. Heritability was 17% for preterm delivery in first pregnancy, and 27% for preterm delivery in any pregnancy. In the former case, however, we could not reject a model without genetic influences. Although our data did not allow for differentiation of the varying aetiologies of premature parturition, results from this exploratory analysis suggest that further investigation of genetic influences on specific reasons for preterm birth is warranted.     

Heritability of Longitudinal Changes in Coronary-Heart-Disease Risk Factors in Women Twins

Numerous studies have demonstrated genetic influences on levels of coronary heart disease (CHD) risk factors, but there also may be genetic effects on the intraindividual variation in these risk factors over time. Changes in risk factors are likely to reflect genetic-environmental interactions and may have important implications for understanding CHD risk. The present study examines the heritability of changes in CHD risk factors, using data from the two examinations by the Kaiser Permanente Women Twins Study, performed a decade apart. The sample consisted of 348 pairs of women twins who participated in both examinations, including 203 MZ pairs and 145 DZ pairs. Average ages at the two examinations were 41 and 51 years, respectively. By means of three different statistical analytic approaches, moderate heritability estimates were demonstrated for changes in LDL cholesterol (h2 = .25-.36) and in HDL cholesterol (h2 = .23-.58), some of which were statistically significant. Although small to moderate heritability estimates were found for systolic blood pressure (.18-.37; P < .05 for some estimates), no genetic influence on changes in diastolic blood pressure was detected. Based on longitudinal twin data in women, this study demonstrates a genetic influence on changes in both lipoprotein risk factors and systolic blood pressure over a decade. In addition to environmental factors, which clearly are operating, the effect of various "variability genes" may be acting independently of the genetic influences on the absolute levels of these risk factors. Both mapping the gene(s) underlying intraindividual variations in these CHD risk factors and understanding their function(s) could lead to targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.     

The influence of zygosity and chorion type on fat distribution in young adult twins consequences for twin studies.

An adverse intra-uterine environment has been associated with abdominal fat distribution in singletons. Twins often have a low birth weight and a short gestation. Therefore, they may have an increased risk to develop abdominal obesity. Furthermore, monozygotic monochorionic twins (MZ MC) have a larger intra-pair birth weight difference compared to monozygotic dichorionic twins (MZ DC). If adult anthropometry is programmed in utero, this may affect the intra-pair correlations in adulthood and, consequently, also the results from the classic twin method to estimate genetic and environmental influences. In the present study, we compared the absolute values, the intra-pair differences, and the intra-pair correlations of body mass, height, BMI, and abdominal fat distribution of 424 MZ MC, MZ DC and dizygotic (DZ) twin pairs (aged 18-34 yrs). DZ, MZ DC and MZ MC twins did not differ for most anthropometric characteristics. Only MZ women tended (p = 0.03) to accumulate more abdominal fat compared to DZ twins. Overall, the contribution of zygosity and chorion type to adult anthropometry was rather low (< or = 1.7%). Although the intra-pair birth weight difference of MZ MC pairs (10.5% in men, 12.3% in women) was significantly larger compared to that of MZ DC pairs (6.9% and 9.2% resp.), the intra-pair differences in adult anthropometry were similar for both MZ twin types. Also the intra-pair correlations of MZ MC and MZ DC pairs were strikingly alike, suggesting no significant influence of the prenatal environment on adult concordance. In conclusion, the substantial difference in the prenatal environment of MZ MC and MZ DC twins did not result in a difference in intra-pair concordance of adult anthropometry and fat distribution. Therefore, we suggest that the chorion type of MZ twins does not bias the twin design and the estimation of the genetic contribution to adult anthropometry.     

A twin study of structural chromosome aberrations in lymphocytes

Structural chromosome aberrations were analyzed in peripheral lymphocytes of eight monozygotic (MZ) and seven dizygotic (DZ) pairs of male twins. There was no significant intrapair difference in the variance of aberration frequencies among the MZ and DZ twins. Thus, there was no evidence of a major genetic influence on the development of structural chromosome aberrations. Although a genetic component could not be excluded, it was concluded that any chromosome aberrations observed were probably due mainly to environmental influences.     

Genetic and environmental influences on bilateral dental asymmetry in Northwest Indian twins

The role of genetic and environmental factors on dental asymmetry (in maximum crown dimensions) was examined using 58 pairs of twins (23 MZ and 35 DZ) from Chandigarh, India. The t'-test for equality of means by zygosity showed only one variable significantly different among 56: this is ascribable to Type 1 error. Heterogeneity of MZ-DZ total variance was observed in 42.9% of traits of the two types (fluctuating and directional) of bilateral asymmetry. In general, MZ twins showed higher total variance than DZ pairs. MZ twins also showed stronger environmental covariance for a majority of the traits. Dental asymmetry measures thus yielded consistently low genetic variance ratios and indicated predominantly complex environmental determinism. Since fluctuating asymmetry is widely believed to be an environmental stress indicator, this data set allows confirmation of methods for detecting unequal environmental influences on the zygosities which bias estimates of genetic variance and heritability.     

Parent ratings of temperament in twins: explaining the 'too low' DZ correlations.

Twin studies of child temperament using objective measures consistently suggest moderate heritability for most dimensions. However, parent rating measures produce unusual patterns of results. Intraclass correlations for identical (MZ) twins are typically high, whereas fraternal (DZ) twin intraclass correlations are much lower than would be predicted from an additive genetic model. The 'too low' DZ correlations can be explained by parent-rating biases that either exaggerate the differences between DZ twins (contrast effects) or that inflate the similarity of MZ twins (assimilation effects), or by the presence of non-additive genetic variance. To evaluate the three possible explanations, we used model-fitting procedures applied to parent-rating data averaged across 14, 20, 24, and 36 months of age in a sample of 196 twin pairs participating in the MacArthur Longitudinal Twin Study. The data were best described by a model that included contrast effects. Implications for non-twin research are discussed.     

Genetic effects in human skeletal muscle fiber type distribution and enzyme activities

The purpose of the study was to estimate the genetic effect for skeletal muscle characteristics using pairs of nontwin brothers (n = 32), dizygotic (DZ) twins (n = 26), and monozygotic (MZ) twins (n = 35). They were submitted to a needle biopsy of the vastus lateralis for the determination of fiber type distribution (I, IIa, IIb) and the following enzymes were assayed for maximal activity: creatine kinase, hexokinase, phosphofructokinase (PFK), lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase (OGDH). For the percentage of type I fibers, intraclass correlations were 0.33 (p less than 0.05), 0.52 (p less than 0.01), and 0.55 (p less than 0.01) in brothers and DZ and MZ twins, respectively. MZ twins exhibited significant within-pair resemblance for all enzyme activities (0.30 less than or equal to r less than or equal to 0.68). In spite of these correlations, genetic analyses performed with the twin data alone indicated that there was no significant genetic effect for muscle fiber type I, IIa, and IIb distribution and fiber areas. Although there were significant correlations in MZ twins for all muscle enzyme activities, the often nonsignificant intraclass coefficients found in brothers and DZ twins suggest that variations in enzyme activities are highly related to common environmental conditions and nongenetic factors. However, genetic factors appear to be involved in the variation of regulatory enzymes of the glycolytic (PFK) and citric acid cycle (OGDH) pathways and in the variation of the oxidative to glycolytic activity ratio (PFK/OGDH ratio). Data show that these genetic effects reach only about 25-50% of the total phenotypic variation when data are adjusted for age and sex differences.     

The mechanism of emergenesis

Since each individual produced by the sexual process contains a unique set of genes, very exceptional combinations of genes are unlikely to appear twice even within the same family. E. O. Wilson (1978)The intraclass correlations of monozygotic twins who were separated in infancy and reared apart (MZA twins) provide estimates of trait heritability, and the Minnesota Study of Twins Reared Apart [MISTRA: Bouchard et al. (1990), The sources of human psychological differences: the Minnesota study of twins reared apart, Science 250, 223-228] has demonstrated that MZA pairs are as similar in most respects as MZ pairs reared together. Some polygenic traits--e.g. stature, IQ, harm avoidance, negative emotionality, interest in sports--are polygenic-additive, so pairs of relatives resemble one another on the given trait in proportion to their genetic similarity. But the existence and the intensity of other important psychological traits seem to be emergent properties of gene configurations (or configurations of independent and partially genetic traits) that interact multiplicatively rather than additively. Monozygotic (MZ) twins may be strongly correlated on such emergenic traits, while the similarity of dizygotic (DZ) twins, sibs or parent-offspring pairs may be much less than half that of MZ pairs. Some emergenic traits, although strongly genetic, do not appear to run in families. MISTRA has provided at least two examples of traits for which MZA twins are strongly correlated, and DZA pairs correlate near zero, while DZ pairs reared together (DZTs) are about half as similar as MZTs. These findings suggest that even more traits may be emergenic than those already identified. Studies of adoptees reared together (who are perhaps more common than twins reared apart) may help to identify traits that are emergenic, but that also are influenced by a common rearing environment.     

Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes.

Lp(a) is a unique lipoprotein consisting of an LDL-like particle and a characteristic protein, apo(a). Increased levels of Lp(a) constitute a risk factor for coronary heart disease. Variation in the size of the apo(a) protein is a phenotype controlled by the apo(a) gene on chromosome 6 and is related to Lp(a) plasma levels. Based on 169 MZ and 125 DZ adult female twin pairs, this study's purpose was to estimate the proportion of the variation in Lp(a) levels that is due to genetic influences and to determine the extent to which the apo(a) locus explains this heritability. Lp(a) levels were significantly more similar in MZ twins than in DZ twins: mean co-twin differences were 3.9 +/- 5.7 mg/dl and 16.0 +/- 19.9 mg/dl (P less than .001), respectively. Intraclass correlations were .94 in MZ twins and .32 in DZ twins, resulting in a heritability estimate of .94 (P less than .001). Heritability was then calculated using only co-twins with the same apo(a) phenotype: the heritability estimate decreased to .45 but was still highly significant (P less than .001). Therefore, on the basis of heritability analysis of women twins, Lp(a) levels are almost entirely genetically controlled. Variation at the apo(a) locus contributes to this heritability, although other genetic factors could be involved.     

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.     

Happy families: a twin study of humour.

The objective of this study was to estimate how much of an individual's appreciation of humour is influenced by genetic factors, the shared environment or the individual's unique environment. A population-based classical twin study of 127 pairs of female twins (71 monozygous (MZ) and 56 dizygous (DZ) pairs) aged 20-75 from the St Thomas' UK Adult Twin Registry elicited responses to five 'Far Side' Larson cartoons on a scale of 0-10. Within both MZ and DZ twin pairs, the tetrachoric correlations of responses to all five cartoons were significantly greater than zero. Furthermore, the correlations for MZ and DZ twins were of similar magnitude and in some cases the DZ correlation was greater than that of the MZ twins. This pattern of correlations suggests that shared environment rather then genetic effects contributes to cartoon appreciation. Multivariate model-fitting confirmed that these data were best explained by a model that allowed for the contribution of the shared environment and random environmental factors, but not genetic effects. However, there did not appear to be a general humour factor underlying responses to all five cartoons and no effect of age was seen. The shared environment, rather than genetic factors, explains the familial aggregation of humour appreciation as assessed by the specific 'off the wall' cognitive type of cartoons used in this study.     

Genetic control of variation in human gingival fibroblast proliferation rate

Summary Logarithmic proliferation rate (Days 1 to 6) of gingival fibroblasts derived from 15 pairs of monozygotic (MZ) and 9 pairs of dizygotic (DZ) human twins was compared under optimal and suboptimal growth conditions. Cell proliferation rates exhibited considerable variability among strains. For Caucasian donors (13 MZ, 6 DZ pairs) DZ twins demonstrated significantly greater (P<0.01) within-pair variance in cell proliferation rate compared to MZ twins when evaluated under optimal growth conditions. Heritability analysis indicated strong genetic control of proliferation rate of human gingival fibroblasts (HGF) under optimal growth conditions (1.0±0.67), whereas proliferation rate of HGF under suboptimal growth conditions revealed less genetic control (0.42±0.61). These findings emphasize the importance of carefully matching control and test HGF in assays dependent on cellular proliferation. This work was supported by grants DE-06671 and DE-07841 from the National Institutes of Health.     

Chorion type as a possible influence on the results and interpretation of twin study data.

The estimation of genetic effects from twin studies usually relies upon the equal environment assumption--that monozygous (MZ) and dizygous (DZ) twin pairs experience equal similarity of their environments from prenatal experiences through adulthood. However, the sharing of a chorion may make a subset of identical twins more similar, or in some cases, more different, than twins that do not share a chorion. Recent studies suggest monochorionic MZ twins resemble one another more than dichorionic MZ twins in cognitive abilities, personality, and risk for psychiatric disorder. To the extent that prenatal environment affects these characteristics, the traditional twin method will yield biased estimates of genetic and environmental influences. We develop models for quantifying this bias and estimating the influence of chorion type on estimates of heritability.     

Skeletal growth and aging parameters due to heredity at different stages of ontogeny

Two hundred and twenty twins of Ukrainian ethnic group have been examined (89 monozygotic (MZ) and 131 dizygotic (DZ) pairs) during peripubertal (42 MZ and 69 DZ) and mature (47 MZ and 69 DZ) age periods. Of them: 94 are male pairs (31 MZ and 62 DZ) and 126 female (58 MZ and 68 DZ) pairs. The program including 16 anthropometric, 48 osteometric and 8 osteoscopic signs has been performed according to the recommendations suggested by D. G. Rokhlin (1936), V. V. Bunak (1941) and B. A. Nikityuk (1968). The hereditary influence on the longitudinal anthropometric signs decreases in mature age with a simultaneous increase of these influences on weight parameters and transversal dimensions of the trunk. Transition from the peripubertal to the mature age is characterised by a decrease of genetic effects on highly-hereditable osteometric signs and an increasing effect of heredity on the skeletal ageing signs. The degree of hereditarily-dependent skeletal ageing is higher in the I mature than in the II mature age, and in the female it is higher than in the male group.     

Inheritance of hypodontia in twins

The aim of this study was to establish prevalence of hypodontia in the twin sample and to assess the degree of its heritability. A study was performed in a sample of 96 twin pairs, 38 pairs being monozygotic (MZ) and 58 pairs dizygotic (DZ), from north-west Croatia. The sample included 25.82% of all twins born in the region during a ten-year period. The twin zygosity was determined according to the WHO recommendations (1996). A revised Holzinger's index (Hc') according to Allen was applied to calculate the degree of heritability. Hypodontia was found in 22 out of the total of 192 twins analyzed (11.5%). Among 96 pairs of twins, hypodontia was observed in 17 pairs (7 MZ and 10 DZ pairs). Among the MZ, 4 pairs were found to be concordant for hypodontia, among the DZ one pair only. The heritability index was 0825. A prevalence of hypodontia in twins observed in this study is significantly higher than in the general population. A high index of heritability (Hc' = 0.825) points to a high genetic determination.     

Twin concordance for a binary trait. II. Nested analysis of ever-smoking and ex-smoking traits and unnested analysis of a "committed-smoking" trait

Twin concordance rates for a binary trait can provide information about causes of trait variation. However, if trait prevalence varies with age (or birth cohort) or between the sexes, trait concordance rates will be artificially inflated because of the matching within pairs of twins. Our previous paper showed how to minimize the effects of such confounding by using logistic regression to model trait prevalence as a function of age and sex and that the binary correlation coefficient was useful as a measure of concordance that can be adjusted for trait prevalence. This method is extended here to allow for nested analyses and is applied to the smoking habits of a sample of 3,807 pairs of adult twins. For monozygotic (MZ) twins, the correlation coefficients for the binary trait of "ever-smoking" (males: .50 +/- .04; females: .60 +/- .02) were significantly greater than for dizygotic (DZ) twins (males: .37 +/- .05; females: .31 +/- .04; unlike-sex pairs: .21 +/- .03). For "giving-up smoking," given that both twins were previously smokers, the correlations for MZ twins (males: .37 +/- .07; females: .29 +/- .05) were also greater than for DZ twins (males: .11 +/- .09; females: .26 +/- .08; unlike-sex pairs: .13 +/- .06), although the difference was not statistically significant for females. Current smokers who had been smoking for at least 10 years were arbitrarily defined as "committed-smokers." The binary trait of "committed-smoking" was more strongly correlated in MZ twins (males: .41 +/- .06; females: .41 +/- .04) than in DZ twins (males: .22 +/- .08; females: .18 +/- .05; unlike-sex pairs: .16 +/- .05). These observations suggest that as well as depending on socially determined environmental factors, smoking behavior is influenced by genetic factors and/or by environmental factors unique to the MZ twin environment, which are of particular importance as determinants of "committed-smoking." There is a need for further research to investigate the personal characteristics of "committed-smokers" and to seek intervention strategies that are more suited to the needs of individual smokers.     

Using bivariate models to understand between- and within-cluster regression coefficients, with application to twin data

In the regression analysis of clustered data it is important to allow for the possibility of distinct between- and within-cluster exposure effects on the outcome measure, represented, respectively, by regression coefficients for the cluster mean and the deviation of the individual-level exposure value from this mean. In twin data, the within-pair regression effect represents association conditional on exposures shared within pairs, including any common genetic or environmental influences on the outcome measure. It has therefore been proposed that a comparison of the within-pair regression effects between monozygous (MZ) and dizygous (DZ) twins can be used to examine whether the association between exposure and outcome has a genetic origin. We address this issue by proposing a bivariate model for exposure and outcome measurements in twin-pair data. The between- and within-pair regression coefficients are shown to be weighted averages of ratios of the exposure and outcome variances and covariances, from which it is straightforward to determine the conditions under which the within-pair regression effect in MZ pairs will be different from that in DZ pairs. In particular, we show that a correlation structure in twin pairs for exposure and outcome that appears to be due to genetic factors will not necessarily be reflected in distinct MZ and DZ values for the within-pair regression coefficients. We illustrate these results in a study of female twin pairs from Australia and North America relating mammographic breast density to weight and body mass index.     

A study of lactose absorption capacity in twins

Summary Lactose absorption capacity was determined by lactose tolerance tests with breath hydrogen determination in 102 healthy, adult, Hungarian pairs of twins in order to test monogenic Mendelian inheritance of the absorptive lactase phenotypes, lactose absorber and lactose malabsorber. Of the total, 52 pairs were monozygous (MZ) and 50 dizygous (DZ) twins of indentical sex. All MZ twins were concordant with respect to lactase phenotype. Among DZ twins, the distribution of lactase phenotypes was in agreement with Hardy-Weinberg expectations derived from the frequencies of the hypolactasia gene in DZ and MZ twins, and in the general Budapest population.In the second part of the study, three commonly used methods of lactose tolerance testing, the blood glucose, the blood galactose, and the breath hydrogen tests, were compared in 49 pairs of twins concordant for lactase phenotype. Blood galactose concentration showed the greatest and only significant difference between the intrapair correlation coefficients of MZ and DZ, and no overlap between lactose absorbers and lactose malabsorbers. The intrapair correlation coefficients of peak breath hydrogen concentration in MZ and DZ twins did not significantly differ from zero, but the resolution of lactase phenotypes was satisfactory. Differences in glucose absorption and concentration in lactose absorbers and malobsorbers overlapped considerably, and among lactose absorbers correlation coefficients in DZ were higher than in MZ twins. In MZ and DZ twins, the difference in concordance and constancy of lactose intolerance symptoms was not significant.     

Genetic influences in self-reported symptoms of obstructive sleep apnoea and restless legs: a twin study.

Sleep disorders, such as obstructive sleep apnoea (OSA) and restless legs syndrome (RLS), are very common. The relative importance of genetic and nongenetic (environmental) influences on the symptomatology of these conditions has not been well studied. This study uses the twin design to examine this by evaluating OSA and RLS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. Six thousand six hundred unselected female twin pairs, identified from a national volunteer twin register, were asked to complete a medical questionnaire. This questionnaire included questions on OSA and RLS symptoms, as well as questions on subject demographics, past medical history, smoking history and menopausal status. Responses were obtained from 4503 individuals (68% response rate). A total of 1937 twin pairs were evaluable: 933 MZ pairs (mean [range] age 51 [20-76] years) and 1004 DZ pairs (age 51 [20-80] years). Concordance rates were higher for MZ than DZ twins for OSA and RLS symptoms. Multifactorial liability threshold modeling suggests that additive genetic effects combined with unique environmental factors provide the best model for OSA and RLS symptoms. Heritability was estimated to be 52% (95% confidence interval 36% to 68%) for disruptive snoring, 48% (37% to 58%) for daytime sleepiness, 54% (44% to 63%) for restless legs, and 60% (51% to 69%) for legs jerking. These estimates dropped only slightly after adjustment for potential confounding influences on the symptoms of snoring and daytime sleepiness. These results suggest a substantial genetic contribution to the symptomatology of OSA and RLS. More research is needed to identify the genes responsible, and may ultimately lead to new therapies.