Role of genetic factors in the formation of trace reactions in man

Trace processes due to presentation of visual nonverbal information, and the dynamics of the bioelectrical parameter (mean level of asymmetry of EEG-waves) were studies in 32 pairs of monozygote and 38 pairs of dizygote twins with twins method. Statistical processing of the data revealed a significant effect of genetic factors on the formation of individual variability of the characteristics of trace processes in humans. The results obtained showed that with increased functional load the intrapair similarity of trace reactions increased in monozygote twins and did not change or decrease in dizygote twins and in unrelated pairs. This fact is interpreted at a dependence of appearance of geneticly determined neurophysiological characteristics on the level of functional activity of the nervous system.     

On the application of queuing theory for analysis of twin data.

A mathematical model based on queuing theory is used to study the dynamics of environmental influence on twin pairs. The model takes into consideration genetic factors and effects of nonshared environment. Histograms are exploited as base analysed characteristics, with the method of minimum chi-square yielding estimated characteristics. The proposed technique was applied to analysis of longitudinal data for MZ and DZ twins. It was shown that the same environment impact may yield different contributions to final variances of the IQ parameters under investigation. Magnitudes of these contributions depend on the genetic factor represented by distributions of an analysed parameter at the point of birth.     

Glucocorticoid receptor binding in twin pairs is affected by shared environment but not by shared genes

We set out to determine whether glucocorticoid receptor activity is affected mainly by genetic or environmental factors. The affinity and capacity of the glucocorticoid receptor was measured using dexamethasone binding in whole leukocytes from 53 monozygotic and 48 dizygotic twin pairs. Receptor binding characteristics assayed from twin pairs on the same day were highly correlated within twin pairs irrespective of zygosity. Apparent Kd was negatively correlated with environmental temperature (R²=0.13, P<0.0001) but this did not confound the intra-pair correlation, suggesting a strong familial component independent of zygosity. Receptor binding parameters were not more closely correlated in monozygotic twins than dizygotic twin pairs indicating that there is no major genetic contribution to receptor binding and that environmental influences predominate. The close similarity in binding between twin pairs in adulthood raises the possibility that familial, non-genetic, factors such as shared early life environment may programme the glucocorticoid receptor.     

Psychophysiologic test performance in normal twins and in a pair of identical twins with essential tremor that is suppressed by alcohol

Summary In a sample of 52 adult male twin pairs (26 MZ, 26 DZ) performance in a series of psychophysiologic tests was measured. The intraindividual variability was determined by repetitive tests in the same subjects. In a number of cases the measured parameters proved relatively stable within the same person; identical twins, however, were no more similar to one another than fraternal twins. In a pair of identical twins with autosomal-dominant essential tremor the degree of the tremor could be effectively reduced by alcohol application.This work was supported by the Deutsche Forschungsgemeinschaft within the SFB 35.     

Application of multiparametric procedures for assessing the heritability of circadian health

At present, the measurement of circadian system status under free-living conditions by the use of sensors is a relatively new technique. The data obtained using these methods are influenced by strong environmental masking factors and artifacts that can affect its recording. Therefore, the use of integrative variables such as TAP, a measure that includes temperature, activity and position that reduces these drawbacks and the number of parameters obtained is necessary. However, the relative genetic contribution to this circadian marker is unknown. The aim of our study was to ascertain the relative importance of genetic influences in TAP, and for each of its components using classical twin models. The study was performed in 53 pairs of female twins [28 monozygotic (MZ) and 25 dizygotic (DZ)] with mean age 52 ± 6 years. Circadian patterns were studied by analyzing temperature, body position and activity for 1 week every 1 min with “Circadianware®.”. Genetic influences affecting the variability of each of the measurements were estimated by comparing the observed data in twin pairs. MZ twins showed higher intrapair correlations than DZ twins for most of the parameters. Genetic factors (broad sense heritability) were responsible for about 40–72% of TAP variance in parameters such as mesor, acrophase, amplitude, Rayleigh test, percentage of rhythmicity and circadian function index. We found more homogeneous heritability estimates of the circadian system when using an integrative technique such as TAP than with individual variables alone, suggesting that this measurement can be more reliable and less subject to environmental artifacts.     

Heritability of human brain functioning as assessed by electroencephalography.

To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilites for the delta, theta, alpha and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans.     

Acquired liver fat is a key determinant of serum lipid alterations in healthy monozygotic twins

Objective: The effects of acquired obesity on lipid profile and lipoprotein composition in rare BMI‐discordant monozygotic (MZ) twin pairs were studied. Design and Methods: Abdominal fat distribution, liver fat (magnetic resonance imaging and spectroscopy), fasting serum lipid profile (ultracentrifugation, gradient gel‐electrophoresis, and colorimetric enzymatic methods), and lifestyle factors (questionnaires and diaries) were assessed in 15 BMI‐discordant (within‐pair difference [Δ] in BMI >3 kg/m²) and nin concordant (ΔBMI <3 kg/m²) MZ twin pairs, identified from two nationwide cohorts of Finnish twins. Results: Despite a strong similarity of MZ twins in lipid parameters (intra‐class correlations 0.42‐0.90, P < 0.05), concentrations of apolipoprotein B (ApoB), intermediate‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein 3a% (HDL3a%), and HDL3c% were higher (P < 0.05) and those of HDL cholesterol, HDL2‐C, and HDL2b% were lower (P < 0.01) in the heavier co‐twins of BMI‐discordant pairs. The composition of lipoprotein particles was similar in the co‐twins. When BMI‐discordant pairs were further divided into liver fat‐discordant and concordant (based on median for Δliver fat, 2.6%), the adverse lipid profile was only seen in those heavy co‐twins who also had high liver fat. Conversely, BMI‐discordant pairs concordant for liver fat did not differ significantly in lipid parameters. In multivariate analyses controlling for Δsubcutaneous, Δintra‐abdominal fat, sex, Δsmoking and Δphysical activity, Δliver fat was the only independent variable explaining the variation in ΔApoB, Δtotal cholesterol, and ΔLDL‐C concentration. Conclusions: Several pro‐atherogenic changes in the amounts of lipids but not in the composition of lipoprotein particles were observed in acquired obesity. In particular, accumulation of liver fat was associated with lipid disturbances, independent of genetic effects.     

Determination of the optimal tissue source and number of microsatellites for detection of zygotic origin of cattle twins

Abstract

Twenty pairs of cattle twins were genotyped for 3 to 12 microsatellites each using semen, blood, milk and hair roots. Chimaerism was recognized in 19 pairs by discrepancies in microsatellite analysis from milk and blood as opposed to semen and hair, or by detection of more than 2 alleles per genotype from milk and blood. Chimaerism of 2, 3 or 4 alleles was demonstrated in genotypes of twins from blood as compared to 1 or 2 alleles only from hair. The appearance of predominant bands in genotypes from blood or milk representing alleles of only one of the co‐twins was not consistent among the different microsatellites for the same twins. No evidence for germ cell chimaerism was found in semen of dizygotic male twins although our PCR system could detect cell mixes as small as a 1:100 ratio. Genotyping from either hair or semen for 4 microsatellites are sufficient to confirm zygotic origin of twins at .98 accuracy. Researchers should be aware of the possibility of erroneous genotyping when analyzing DNA from twins derived from blood or milk and the potential of chimaerism as an experimental model to study different immunological characteristics of cattle co‐twins.     

Challenges in recruiting older twins for the Sri Lankan twin registry.

The National Twin Registry of Sri Lanka was established in 1997 as a volunteer register. To extend it to a population-based register, we examined the effectiveness of tracing older twins by inspecting birth records and recruiting them by postal invitation and in-person contact. Birth records at a divisional secretariat reported from 2 maternity hospitals between the years of 1954-1970 were scrutinised to identify a random sample of twins. These hospitals had the highest twin delivery rates for the whole country. We identified 620 twins and a questionnaire was mailed to them. Research assistants visited a cohort of non-respondents (71) in the postal survey. These 620 twins were identified after perusing 20700 birth records. The twinning rate was estimated at 29.95 ([620/20700] x 1000) twins per 1000 registered births (CI 27.63-32.27). In the postal survey, 37 (12%) responded and 62 letters were returned (20%). Both twins were still alive in 20 pairs, one was still alive in 15 pairs, and both twins were dead in 2 pairs. During field visits, 42 (59.2%) addresses were located. Information was available on 16 twin pairs. Both twins were alive in 8 pairs, one each in 4 pairs, and both were dead in 4 pairs and at least one twin was traced in 10 pairs (14%). Both the postal and the field survey gave a low yield. This finding is different from tracing younger twins born between 1985-1997 by using the same methods. Migration, urbanization and development in the country might have affected tracing older twins from the birth record addresses, which were decades old.     

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.     

Characteristics of a Japanese adult twin database of high school graduates.

This paper profiles a unique cohort of adult Japanese twins. The database contains more than 700 twin pairs, aged 18 to 66 years, who are all graduates of the secondary school attached to the faculty of education of the University of Tokyo. This school was established in 1948, when the study of twins was burgeoning in Japan, and about 10 to 20 pairs of twins have been admitted there every year to participate in studies on twins in education and in related projects. The zygosity of all twins was determined carefully on the basis of various sources. Data from the perinatal period to adulthood were linkable using ID numbers. Follow-up surveys in the field of medical genetics were performed in 1985, 1989 and 1999. For the third survey, which was sent and received exclusively by mail, the distribution and collection process was also assessed in detail. The response rate was around 40%, which statistically was influenced mainly by previous participation and sex. The limitation of this cohort is its selection bias concerning socioeconomic status and its imbalance in favor of monozygotic pairs.     

Categories of deltaF508 homozygous cystic fibrosis twin and sibling pairs with distinct phenotypic characteristics.

Cystic fibrosis (CF), the most common severe autosomal recessive trait among Caucasians, is caused by molecular lesions in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The course of the multi-organ disease CF is highly variable, suggesting the influence of environmental factors and/or modulating genes other than CFTR on the disease phenotype. To evaluate the cause of CF disease variability, the European CF Twin and Sibling Study collected data on two clinical parameters most sensitive for the course and prognosis of CF, ie weight predicted for height (wfh)% (representative for the nutritional status) and FEVPerc (representative for the pulmonary status) for a cohort of 277 sibling pairs, 12 pairs of dizygous twins and 29 pairs of monozygous twins. Of these 318 CF twin and sib pairs, 114 were reported to be homozygous for the most frequent CF disease-causing lesion, deltaF508. Intra-pair discordance was assessed by the intra-pair differences with wfh% and FEVPerc and by DELTA, a composite parameter defined by linear combination of wfh% and FEVPerc in order to describe discordance with respect to the overall disease severity. Monozygous twins had a significantly lower DELTA than dizygous twins (P = 0.05) indicating that CF disease severity is modulated by an inherited component in addition to the CFTR gene itself. Extreme phenotypes are considered to be more informative for the analysis of any quantitative trait. Thus, we aimed to quantify disease severity and intra-pair discordance in order to select pairs with the extreme phenotypes DIS (discordant patient pairs), CON+ (concordant and mildy affected patient pairs) and CON- (concordant and severely affected patient pairs). The algorithm reliably discriminated between pairs DIS, CON+ and CON- among the cohort of deltaF508 homozygotes. The selected pairs from these categories demonstrated non-overlapping properties for wfh%, FEVPerc and the intra-pair difference of both parameters.     

Viruses and the aetiology of diabetes: a study in identical twins.

Sera were collected from 49 pairs of identical twins, 27 of whom were discordant (only one twin affected) and 22 concordant (both diabetic) for insulin-dependent diabetes. All were tested for antibodies to mumps, cytomegalovirus, rubella, Coxsackie virus types B1-5, and Mycoplasma pneumoniae. The diabetic co-twins had no more antibodies to any of the viruses than the non-diabetic co-twins of the discordant pairs. Antibodies to Coxsackie B2, rubella virus, and M pneumoniae were found more often in the discordant than in the concordant twins. In 30 of the 71 diabetic twins symptoms began when they were aged 4-6 years or 10-15 years. More concordant than discordant twins were diagnosed during the months January to March. Hence there was no direct evidence of a virus aetiology of juvenile onset diabetes in these twins, and the difference in antibody titres between the concordant and discordant twins was in keeping with a genetic difference between them. The age and time of onset suggested that environmental factors may be important in causing diabetes in the twins.     

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.     

青少年双生子体型指征相关指标的遗传度研究(英文)

目的:用经典的双生子设计探讨遗传因素对青少年身高、体重、体质指数(BMI)等体型指征的影响程度。方法:从青岛市双生子库中选择自愿参加本研究的362对11-19岁双生子,测量身高、体重。同性别的双生子通过16个多态标记进行卵型鉴定,在此基础上,应用Mx软件构建结构方程模型分析计算遗传度。结果:对362对有效双生子数据进行分析,其中同卵双生子194对,异卵双生子168对,身高的最佳拟合模型ACE模型,体重和BMI的最佳拟合模型为AE模型。调整年龄性别后,身高的遗传度为66%,体重的遗传度为84%,体质指数的遗传度为75%。结论:在青少年体型指征的相关指标中,身高、体重、BMI受遗传因素影响都较大。     

Detection of leucochimaerism in bovine twins by DNA fingerprinting

Karyotyping and hypervariable genetic markers indicate extensive leucochimaerism between pairs of dizygotic twins in cattle, a result of placental vascular anastomosis. The extent of this chimaerism includes both kind and number of cells exchanged. All heterosexual twin pairs harboured two types of leucocytes, having either XX or XY chromosome pairs, and 30 of 31 pairs of twins shared identical DNA fingerprints. Although chromosome results from skin fibroblasts indicate that some chimaerism occurs in the skin, the low level allows for differentiation of genotypes between twins. The results warrant against the common practice of using blood samples for DNA typing if twinning is not properly documented.     

The role of hereditary and environmental factors in the variability of the components comprising the mass of the human upper extremity at various stages of postnatal ontogeny

The investigation has been performed in mono- and dizygotic twins of the Ukrainian ethnic and territorial groups. As a whole 196 pairs of twins, among them 80 pairs of mono- and 116 pairs of dizygotes of both sex at the age of 12-60 years have been undergone the examination. The twins selected are divided into two age groups--period of sex maturation (12-17 years of age) and that of maturity (30-60 years of age). Quantitative parameters on composition of the components of the upper extremity mass (fatty, muscular and osseous) are studied in all the twins. Coefficients of intrapaired correlation and indices of Holzinger's heritability are calculated according to an original program, using the microcomputer "Electronika B3-34". The degree of hereditary and environmental influences for development and formation of the main components of the upper extremity mass at certain stages of individual development are characterized with ontogenic changeability. With age the degree of hereditary dependence of the development and formation of the upper extremity mass components decreases, and sex dimorphism according to the degree of the hereditary dependence of the components studied is displayed as a greater hereditary determination in male persons.     

Manifestations of the genotypic causality of human evoked potentials during perception of various visual stimuli

Intrapair resemblance of the wave form and amplitude-temporal parameters of evoked potentials (EPs) to flashes, chess field, house image, the word "house" and a series of other stimuli was evaluated in 20 pairs of monozygotic and 20 pairs of homosexual dizygotic adult twins. In the occipital area the maximum of genetic dependence was characteristic of EPs to flashes, the minimum--of EPs--to the word "house". In vertex EPs parameters genotypic effects were manifest irrespectively of the stimulus type. Genotypic dependence differed for the amplitudes and latencies of separate EP components.