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The program of any individual's vital cycle encoded in the genetic information is executed according to a time schedule that is the object of study of Chronogenetics. MZ twins provide the best evidence of the existence of this hereditary biological time and they represent, therefore, the natural test of Chronogenetics. Twin research can thus serve medicine in developing its most modern perspective, individual preventive medicine. Moreover, through approaches such as the Twins-Living-Apart Test, twin research can help to identify the influences of the environment on the health of man.
The ongoing comprehensive study of the updated population-based Norwegian Twin Panel (like-sexed twin pairs born since 1915) has already given results of interest to the research on coronary heart disease and its risk factors. Significantly more dizygotic (DZ) than monozygotic (MZ) pairs are discordant for death between 40 and 60 years of age. Presumably, several of the cases must have been coronary heart disease deaths. In pairs where both members are alive, concordance rate for coronary heart disease before the age of 60 years is significantly higher in MZ than in DZ pairs. Concordance rate for reported hypertension is significantly higher in MZ than in DZ pairs. These findings are compatible with a significant genetic effect on premature death, coronary heart disease and hypertension.
There is a strong genetic effect on serum level of apoB, apoA-I and apoA-II, a weaker effect on cholesterol level and a doubtful effect on triglyceride level. Genes belonging to several normal genetic polymorphisms may participate in the control of environmentally/dietary caused variability in lipid and lipoprotein parameters. The study of MZ twins that was conducted to detect these effects holds considerable promise for the detection of gene control of many kinds of quantitative parameters. Further work with this twin panel may provide more definite answers to several questions raised during the present investigation. Application of more sophisticated models for twin family analysis on several normal and pathological traits may be very informative. Also, this updated Norwegian Twin Panel should in the long run make it possible to estimate the predictive value for the second member of a twin pair of having a twin contracting coronary heart disease (or any other reasonably frequent disease) by a given age. Finally, the subsample that is subjected to extensive laboratory analyses will provide useful data for genetic linkage analyses since in many cases, offspring of two members of a MZ pair can effectively be considered as one single (more informative) sibship.
In order to estimate genetic variance and heritability of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum cholesterol and triglyceride levels, a total of 235 (79 male and 82 female MZ, 41 male and 33 female DZ) twin pairs, recruited from 12 junior high schools in Taipei city, were studied. Statistically significant genetic variance observed for SBP, DBP, serum cholesterol and triglycerides persisted after adjustment for age and anthropometric characteristics. However, further adjustment for dietary preference, beverage consumption, and other host and environmental factors gave different results: genetic variance of adjusted SBP and DBP was still significant, while significance was found only in males for cholesterol and in neither males nor females for triglycerides. Heritability estimates of unadjusted SBP, DBP, cholesterol and triglycerides were 0.27, 0.45, 0.21 and 0.41, respectively, for males, and 0.15, 0.42, 0.41 and 0.82, respectively, for females. After adjustment for age, anthropometric characteristics, host and environmental factors, the heritability estimates of SBP, DBP and cholesterol were 0.64, 0.72 and 0.50, respectively, for males, and 0.40, 0.60 and 0.37, respectively, for females.
The monozygotic (MZ) cotwin control method was employed to elucidate possible environmental determinants of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum cholesterol and triglyceride levels. A population-based twin sample of 73 male and 77 females MZ twin pairs was recruited from 12 junior high schools in Taipei city. Intrapair differences in blood pressure were negatively associated with intrapair difference in vegetable preference, attaining significance for DBP in males and SBP in females. Cholesterol was positively associated with milk consumption and preference for sweets, fried foods, meat and fish. A negative association was also observed between choleserol and vegetable preference. These associations for cholesterol were significant in males only. Triglyceride level negatively associated with preferences for sweets and vegetable, attaining significance for vegetables in both males and females and for sweets in males only.
A population-based sample of 73 male and 77 female monozygotic (MZ), and 41 male and 33 female dizygotic (DZ) Chinese adolescent twin pairs were studied to assess effects of gene-environment interactions of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum cholesterol and triglyceride levels. Intrapair concordance in BP levels was found to be significantly associated with the interaction of zygosity and salty foods preference and also with that of zygosity and vegetable preference. A consistently positive and statistically significant association was observed between the intrapair difference in serum cholesterol and the interaction of zygosity and animal organ preference; while intrapair concordance in serum cholesterol was associated with the interaction of zygosity and milk consumption. Intrapair difference in serum triglycerides was associated with the interaction of zygosity and fish preference, and a significant association was also found between the intrapair concordance in serum triglycerides and the interaction of zygosity and sweets preference. These observations suggest that the impact of these environmental agents may be influenced by the genotype.
High resolution tracings of atrial depolarization can be obtained by surface signal averaging technique. A study was conducted on 4 male and 4 female healthy MZ twin pairs aged 10.4 ± 1.3 yrs. Each subject underwent 3 or more recordings, at 10-days intervals. The essential reproducibility could be confirmed, with personal characteristics, as well as the reliability of the technique and the electrophysiological value of the spikes complex. In 3/8 pairs the cotwins showed a significant likeness of the atriogram, while in 5/8 pairs the tracings were not quite resembling between the twins and that is attributed to variations in the chronogenetic characteristics of MZ twins.
A Cox proportional hazard regression analysis was carried out that evaluated age-specific death risk among 21,890 twins born in Sweden during 1886 through 1925 and followed during 1962 through 1980. Cotwin's survival was used as the primary covariable, and auxiliary covariables were smoking, marital status and, among men, police registration for alcohol abuse. In each age, sex and zygosity group, except the oldest DZ males, cotwin's mortality had a significant, independent, positive relationship to the mortality risk of the individual. The auxiliary covariables, except marital status among females, had significant, independent, positive relationships to mortality among the youngest twins of both zygosity groups and in the middle age group of MZ twins. In the oldest age group, the death of MZ cot wins was the only variable significantly related to the individual's mortality. Heritability estimates for the age-specific probability or death risk, developed by different methods for different analysis groups, range between 0.4 and 0.6. They have reasonable internal consistency, are not much affected by the covariates, and are in agreement with other studies that did not control covariates.
Data from the young cohort of the Swedish Twin Registry are being used in an attempt to describe characteristics which distinguish among current, non- and ex- smokers prior to the development of a smoking habit versus those present after establishment of the habit (or lack of one). With twins as a sample of individuals, the psychosocial variables instability, extroversion, leisure activity, relative weight, alcohol, coffee and psycho-pharmaceutic drug use were examined jointly as predictors of current smoking status in multiple regression analyses. This phase was intended to replicate and expand upon earlier studies characterizing current, non- and ex-smokers. These analyses were then performed on MZ nonsmoking twin individuals who were classified on the basis of their cotwins' smoking status. Pattern of variation in the psychosocial variables across the groups of nonsmokers were similar to the pattern seen for current, ex- and nonsmokers. Characteristics in MZ nonsmokers which are predictive of their cotwins' smoking status may be interpreted as those present prior to development of a smoking habit. Selected results from these analyses will be presented.
Data on alcohol use and smoking habits was available from the 1975 questionnaire of the entire cohort. Prior to pairwise analyses, the data of individuals was compared to that of age-sex matched groups of pairs reared together. The early separated twins had a higer alcohol consumption, while for smoking only slight differences were observed compared to twins reared together. Probandwise concordance rates were computed from smoking status (ever smoker/never smoker), alcohol use (user/nonuser) and “heavy” drinking (half-bottle of spirits on one occasion at least once a month). The following results were obtained in those pairs with the environmental dissimilarity score > 15:
A genetic analysis of alcohol consumption in 3810 pairs of adult twins is reported. When no correction was made for age, individual environmental variance, including non-repeatable errors of reporting, accounted for approximately 44% of variation in both sexes. In females, there was no evidence of shared environmental effects and 56% of the variance was genetic in origin. In males, only 36% of the variance was genetic and common environmental effects accounted for the remaining 20% of individual differences.
For females, the results for younger (30 years and under) and older (over 30) twins were similar. For males, however, the effect of age was striking. In younger male twins over 60% of the variance was genetic in origin, with the remaining variance due to environmental influences unique to the indiviudal. In older twins genetic differences do not appear to be important, with approximately 50% of the total variance due to individual environmental differences and the remaining 50% due to the effect of the common family environment. Our results suggest that both age and sex need to be considered when analysing the causes of variation in alcohol consumption.
Twelve pairs of MZ and 7 of DZ normal adult male twins were given a challenge dose of 0.8 mg ethanol per kg body weight diluted to a 30% v/v solution. Measures of blood alcohol, mood, craving for alcohol, body sway, heart rate and four psychomotor tasks were taken before, during and after intoxication. Genetic factors were found to be involved in the response of heart rate, body sway and two of the psychomotor tasks, but not in changes in blood alcohol, alertness or craving for alcohol. Drinking habits did not exert a strong influence upon acute responses to alcohol, but were significantly related to craving for alcohol whilst intoxicated.
It is shown that sex- and age-specific death rates from all causes of death other than neoplasms have features that resemble those of corresponding rates for all neoplasms. The same generalization holds in connexion with specific neoplastic and non-neoplastic disorders. In both categories of disease many age-patterns suggest that the rate-governing mechanism for their occurrence is stochastic in character; a rather small number of random events, generally fewer than ten, suffice for their initiation. It is not immediately obvious how a widespread degenerative disorder, sometimes involving an astronomical number of target cells, can be initiated by only a few random events. We infer that all such disorders, together with natural cancers, are autoaggressive in nature. They are initiated by random somatic mutations in comparator stem cells of the central system of growth control. Mutant stem cells propagate forbidden clones of cells that attack target cells at one or multiple sites. (In certain disorders, the presence of an extrinsic precipitator in the host in essential to the propagation of forbidden clones). Autoaggressive attacks have consequences that range from the destruction of target cells to their transformation with invasive proliferation. Senescence can be regarded as the cumulative effect of predominantly late-onset autoaggressive disorders. The relevance of studies of twins to this unified theory is discussed.
Fasting blood glucose and serum immunoreactive insulin (IRI) and the responses of blood glucose and serum IRI to peroral glucose challenge were investigated in middle-aged normoglycemic male twins of 17 monozygotic (MZ) and 18 dizygotic (DZ) pairs recruited from the Finnish Twin Cohort Study. Also, the role of obesity and diet in the regulation of glucose and insulin metabolism was estimated. The fasting and 2 hr postprandial (PP) glucose showed higher pairwise correlations in MZ (r =0.78 and 0.56) than DZ (r = 0.08 and −0.05) pairs whereas fasting and PP insulin levels and the areas under the PP glucose and insulin curves were weakly and similarly correlated in MZ and DZ twins. The pairwise correlations of the 1/2 hr and 1 hr, but not the fasting and 2 hr insulin/glucose ratios, were somewhat higher in MZ (R = 0.51 and 0.53) than DZ (r = = 0.28 and 0.30) pairs. In MZ twins, the intrapair differences in the body mass index were significantly correlated with those in the fasting and 2 hr PP glucose and insulin levels and those in the fasting and 1/2 hr insulin/glucose ratios (r from 0.47 to 0.76). Also, the intrapair differences in the dietary fat calories were correlated positively, but those in the calories derived from carbohydrates negatively, with the intrapair differences in several parameters of the glucose and insulin metabolism. These data suggest that the environmental contribution to the regulation of glucose and insulin metabolism in subjects within the normoglycemic range may be quite strong. Of the environmental factors studied, obesity and dietary fat consumption seem to have powerful regulatory roles, particularly in the response of insulin to the glucose load.
Six skinfold measurements, and percent body fat and fat-free weight derived from the underwater weighing technique were obtained in 43 pairs of male and 44 pairs of female monozygotic (MZ) twins. A fat tissue biopsy was performed in the suprailiac region in 20 male and 16 female pairs in order to determine mean adipocyte diameter and basal lipolysis as well as epinephrine maximally stimulated lipolysis (10−4 M). Twin resemblance in body fatness is clearly demonstrated by the analysis of the between MZ sibships over the within MZ shibship means of squares for all skinfold measurements, percent body fat and fat free weight (P < 0.01). Within MZ pair similarity is as high in female as in male pairs for body fatness. Moreover, members of the same twin pair resemble one another significantly for fat cell size and fat cell lipolytic activities, particularly when epinephrine stimulated. In female MZ pairs, additional studies with control over the menstrual cycle are needed to clarify the case of isolated fat cell basal lipolysis.
In an attempt to uncover the causes of variation in birth weight for 13,970 offspring of MZ and DZ twins, several models were tested. Mean squares from nested analysis of variance were analysed with respect to fetal and maternal effects on variation in birth weight. The major part of the total variation in birth weight was found to be due to effects of genes. The contribution of fetal genes was larger than the contribution of maternal genes. About 11% of the variation could be attributed to effects of interactions between fetal and maternal genes. However, in this data set, the interaction variance could not be distinguished from variance due to fetal dominance or to effects of common environment of sibs.
Establishment of the Kaiser- Permanente Twin Registry permitted the study of disease heritability in twins based on review of the twins' medical records. The records of 930 pairs of twins were reviewed. Based on previous questionnaires, 342 pairs were MZ, 345 were DZ and 243 were of unknown zygosity. Because of the age distribution of these twins and the time period in which they received care, conditions of youth, such as acne vulgaris were most reliably studied Heritability of acne was assessed in three ways; all indicated a substantial genetic influence. Certain problems with twin studies using medical records became apparent: 1) Zygosity information is often lacking; 2) Differing times and durations of observation of the two twins in each pair must be accounted for; 3) Categorization by diagnosis is difficult and strict criteria for diagnosis may be impractical; 4) Patients' behavior that affects assessment of disease concordance must be considered; 5) The order in which records are reviewed may influence apparent concordance.
A concordance study of 6 infectious diseases of childhood has been carried out in a sample of 656 twin pairs classified by sex and zygosity. A new approach is proposed to estimate the respective influence of heredity and of common environment. The estimates thus obtained range from 86% hereditary component in the case of measles to 100% environmental component in the case of scarlet fever.
A case of monozygotic male twins discordant for skeletal and cardiac defect is reported. One twin had the hemifacial microsomia type of the oculo-auriculo-vertebral dysplasia. The cotwin had no asymmetry of the face and normal ears, but preaxial polydactyly and ventricular and auricular septal defects. The cotwins were concordant for craniostenosis with a ridge metopic suture. Karyotypes were normal.
Results on genetic variability in some of the morphometric characters on head and face, body girths and skin folds, based on 45 MZ and 67 like-sex DZ twin pairs, are presented. The data were subjected to a method which eliminated possible biases in the estimated genetic variances that could result from heterogeneity of total variances between zygosities of the 17 head and face measurements, heterogeneity was observed for only bizygomatic diameter. Head breadth means differed between MZ and DZ twins, indicating bias in the trait's genetic variance analysis. The results indicated a significant genetic component in these morphometric traits. For 11 girth and skinfold measurements, the t'-test based on hierarchical structure of twin data, also failed to reveal any appreciable difference between the mean values of MZ and DZ twins. Heterogeneity of total variance between zygosities was observed for three skinfold measurements, ie, biceps, triceps and suprailiac. The girth measurements, however, did not reveal any heterogeneity of total variances between the zygosities. The estimates of genetic variance revealed stronger genetic component for the girths than for the skinfolds.