Traditional twin studies have resulted in higher concordance rates for premature coronary heart disease (CHD) in MZ than in DZ twin pairs. This is in agreement with strong evidence from several other studies, that genetic factors are of importance in the etiology of early onset CHD. Also, in a study of 291 Norwegian twin pairs the concordance rate for hypertension wa 0.36 in MZ and 0.08 in DZ pairs. Relationship between diseases and traditional gene markers have been extensively studied and several associations have been uncovered for CHD. Our group has developed a method to examine a possible permissive or restrictive effect of single genes on the degree of variation that environmental and/or life style factors can cause in a given parameter. This method for studying gene-environment interaction is based on the fact that MZ twins are identical with respect to genes, so that any difference between the two members of an MZ pair must necessarily be caused by environmental or life style factors. The possibility that a given gene influences the degree of variability in a parameter such as cholesterol is examined by comparing the within-pair difference in cholesterol level between MZ pairs possessing, and MZ pairs lacking the gene in question, and results of such studies will be presented. New possibilities to study restriction fragment length polymorphisms (RFLPs) at apolipoprotein loci have added a new dimension to research on genetics of CHD and hyperlipidemias. Association between apolipoprotein B, cholesterol and fasting triglyceride levels on one hand and DNA variation at the apolipoprotein B locus on the other has been found. We have studied RFLPs at apolipoprotein loci in twin families. The results are presented.

An interdisciplinary study, in adult twins and their family members, of the genetic and environmental determinants of complex physiologic functions is in progress. This report summarizes our initial studies of the control of the level of systolic (K1) and diastolic (K5) blood pressure in 202 monogygotic (MZ) and 121 dizygotic (DZ) twins, their spouses and their children. Correlation coefficients for blood pressure were adjusted for the covariates age, sex, body mass index (wt/ht2) and screener, all of which significantly augment most correlations. These adjusted correlation coefficients in MZ twins are 0.5 for both K1 and K5 blood pressure. For DZ twins, the adjusted correlation coefficients are 0.21 (K1) and 0.24 (K5). MZ twin-offspring adjusted correlation coefficients are higher than MZ twin-niece/nephew adjusted correlation coefficients (0.12 and 0.06, respectively, for K1; 0.20 and 0.13, respectively, for K5), despite the genetic identity of these relationships. That environmental factors may explain these differences is suggested by other differences in adjusted correlation coefficients that are greater than those predicted by the degree of genetic similarity. In addition, we have assessed the relationship between two biochemical-physiological processes, the urinary excretion of kallikrein and transport of sodium in the erythrocyte (the sodium countertransport and the sodium-potassium-chloride cotransport systems), and blood pressure control, since both have been implicated in the control of blood pressure level. Although we found evidence for substantial genetic control of both phenomena, we were unable to establish any correlation between either function and the level of blood pressure in our normotensive subjects.

These data point to the operation of three broad categories of control of level of blood pressure: constitutional factors (age, sex, body mass), genetic factors and environmental factors. The identities of the genetic and environmental factors are unknown at this time.

In an earlier study of blood pressure variation in middle aged parents and their young adult twin offspring, the greater blood pressure variation observed in the parent sample was accounted for in terms of an increasing influence of individual environmental experiences with increasing age and a commensurate reduction in the impact of heredity. In the present study, the sample size was enlarged to provide a more powerful test of these effects. Maximum likelihood model-fitting techniques were applied to blood pressure covariation in balanced pedigrees, consisting of 85 families (40 MZ and 45 DZ twin pairs). As before, our analysis indicated that a developmental effect was a salient factor in the older age group.

Observed increases in phenotypic variance for blood pressure during adulthood are a predictable consequence of an a priori model for developmental change and continuity previously applied to cognitive development. The implications of this model for genetic and environmental covariances depend on the mechanism which maintains developmental continuity. Using data from young adult twins and their parents, it is shown how traditionally estimated genetic and environmental parameters may be reinterpreted in the light of the developmental model. Illustrative data suggest a hypothesis that genetic effects on blood pressure are largely temporally pleiotropic, acting consistently but not cumulatively throughout adulthood, while environmental influences act haphazardly but their effects are transmitted forward with high fidelity.

A total of 198 pairs of monozygotic twins reared apart and together were surveyed on their lifestyle and blood pressure through mailed questionnaires. The age of the subjects ranged from 47 to 87 years. The intrapair concordance rate on blood pressure increased from 51% (age of separation 0-5) to 78% (age of separation 26 and over) as the age of separation advanced. The concordance rate on occupation was 59% at the age of separation 0-5 and 87% at the age of separation 26 and over. The intrapair concordance on the food intake (egg, meat, fish, milk and salty seasoning) was positively correlated with the age of separation. Hayshi's quantification theory III (multivariate analysis) was used to claryfy the lifestyle pattern in 39 MZ pairs discordant on blood pressure. There were three factors (meat, milk and occupation) which were closely related with each other in the “non-hypertensive” twins, while lifestyle were not patterned in the “hypertensive” twins. The concordance rate of these three items increased along with the rise of concordance rate of blood pressure as the age of separation advanced.

A total of 543 like-sex pairs of twins (407 MZ, 136 DZ) were sent mailed questionnaires on cigarette smoking, alcohol drinking and health conditions. The observed concordance rate for alcohol drinking was significantly higher than expected in both MZ and DZ pairs. The observed concordance rate for cigarette smoking was significantly higher than expected in the MZ, but not the DZ pairs. The observed rate of intrapair concordance for drinking was significantly higher than expected even in MZ pairs reared apart from infancy or very early childhood. Higher life satisfaction was observed more often in the higher alcohol consumers than in the lower consumers among MZ pairs discordant for alcohol drinking, while earlier onset of presbyopia was observed more often in the lower consumers. Physical symptoms, especially pains in the upper extremities, were reported more often by higher alcohol consumers than by lower consumers in the MZ pairs discordant for drinking.

Eighteen pairs of monozygotic twins discordant for long-term occupational exposure to organic solvents were examined for disturbances of cardiovascular reflexes. All of the subjects were asymptomatic, and considered themselves healthy. No significant differences were observed between the exposed and the nonexposed twins. The finding suggests that occupational solvent exposure at these particular levels is unlikely to cause disturbances of the autonomic nervous function.

Levels of immunoglobulins IgG, IgA, IgM and IgE were determined in 8 MZ and 14 DZ twin pairs at the ages of 6-11 years, 12-17 years and 15-20 years. Intrapair similarity in immunoglobulin levels was found to be higher in the MZ than in the DZ twins, especially in the case of immunoglobulins IgA and IgM.

Urinary pepsinogen A (PGA or PG I) phenotypes and serum PGA levels were studied in MZ and DZ twins and their parents. In 45 out of 48 MZ twin pairs PGA patterns were completely identical, while 3 MZ twin pairs showed minor differences in the relative intensity of the Pg5 isozymogen. This suggests that the intensity of this isozymogen may be influenced by nongenetic factors. There was little difference in the interclass correlations of serum PGA levels between MZ and DZ twins, indicating a large contribution of common environmental factors to serum PGA levels. This is in contrast with previous studies.

Record linkage of the Finnish Twin Cohort Study with the Hospital Discharge Registry and with the Registry of Rights to Free Medication kept by the Social Insurance Institution gave following numbers of twin pairs with an ophthalmic disease (one or both members of the pair had the disease) in each disease category:98 with glaucoma simplex (5 concordant pairs), 38 with capsular glaucoma (no concordant pairs), 58 with iritis (no concordant pairs) and 149 with strabismus (2 concordant pairs).

The number of concordant pairs in each disease category was small, except for glaucoma simplex in which concordant pairs could be broken down by zygosity. The ratio of observed to expected (based on association by chance) was 6.96 for MZ and 1.74 for DZ pairs. This result suggests that genetic factors play some role in the variability of prevalence of simple glaucoma. Main etiologic factors are stili to be found in the environment. Data on occurrence of other diseases of ophtalmologic importance is presented.

In order to reassess the relative importance of genetic and environmental factors in the development of myopia in Chinese schoolchildren, 90 pairs of MZ and 36 pairs of like-sex DZ twins were enrolled for detailed ophthalmological examination about their ocular refractions. Corneal curvatures and axial lengths were also measured. With equivalent settings of the range for concordance, corneal curvatures showed higher concordance rate (84%) than ocular refractions (65%) and axial lenghts (59%) in MZ twins. F-test on the intrapair variances between MZ and DZ twins revealed a significant hereditary role in determining the ocular refraction and its optical components. The degree of genetic determination was expressed by heritability indices, which were derived from intraclass correlation coefficients. The diversity of sample ages and refractions, while making the obtained data difficult to further explore the gene-environment interaction, led to the observation of more intrapair differences with age and myopic progression in MZ twins.

Information about menstrual cycle variables was obtained by questionnaire using 462 female twin pairs. The twins were either members of the Institute of Psychiatry Volunteer Twin Register, or of the Birmingham Population-based Register. The two samples were analysed separately using univariate and multivariate methods so that an independent replication was obtained. Maximum likelihood estimation was used to fit simple models of genetic and environmental variation to these data. The results suggest that age of menarche, menstrual cycle regularity and premenstrual symptom reporting may be heritable, whereas menstrual cycle length is not. The results should be interpreted with caution as not all variables were replicated in the smaller sample, and the method of retrospective menstrual cycle data collection has been questioned.

To study genetic contribution to complex body size traits, the intrafamilial correlation and regression analyses along with twin study method have been used. The data are based on a sample of 45 MZ and 101 DZ twin pairs, their 125 singleton siblings, 104 fathers and 103 mothers in 146 Punjabi families living in Chandigarh, India. Twin study gives no evidence of inequality of means and variances between zygosities. Within-pair genetic variance ratios, correlations, regressions of offspring on midparent and single parent are all significant at 0.1%, thus indicating strong genetic component. Heritability estimates are higher for longitudinal body traits than the breadth dimensions. The resemblance of the children with the parents of either sex is not equal. Higher maternal influence is indicated for a number of body traits. The results on familial correlations do not support the hypothesis of sex-linked inheritance for any of the traits considered in this investigation. These results have been compared with those from other such studies.

A sample of 122 twin pairs and 166 singletons from the urban Punjabi population of Chandigarh was studied. The observed frequency of double occipital hair whorls was higher in twins than in singletons (P < 0.01). The possible association between twinning and double occipital hair whorls is discussed.

Using high-resolution electrocardiography (HRE), we have previously examined the morphological aspects of the atriogram in a set of DZ triplets comparing the MZ and the DZ pairs [3]. We now repeated the recordings on the triplets, three years after the first studies, in order to evaluate the individual morphological reproducibility of the atriogram and the cardiovascular response to effort and to stress by means of provocative tests [1-3].

We studied a set of female DZ triplets aged 15 years, born normally at the 39th week of gestation, with two chorions and three amnions. We compared the responses to the individual provocative tests, and repeated the analysis of the atriograms after three years. We therefore used the HRE, the Bruce protocol ergometric test, and the sympathetic stimulation tests: handgrip test, cold pressure test, arithmetic mental test (Table).

We previously studied a pair of MZ twins with situs viscerum inversus of the heart, liver and stomach, concordant with regard to all other factors normally utilized to diagnose zygosity [3]. We have now reexamined them after three years to evaluate the development of their cardiovascular system.

Our male MZ twins, now 17 years old, have been examined with high-resolution electrocardiography (HRE), treadmill stress test with Bruce protocol, tests stressing the cardiovascular system (cold pressure test, handgript test, arithmetic mental test), and single and two-dimensional dynamic echocardiography after holter monitoring.

Atriogram analysis is made possible by HRE, that shows individual morphological reproducibility. Such reproducibility is present in both twins. In the dextrocardiac twin it is also present with the electrode position inverted. The similarity of morphology in the cotwins is further confirmed, even if such similarity is only apparent, in view of the fact that the vectors are spatially of opposite orientation, thereby causing an inversion of the electrical field [1-4]. The H-V interval is normal, although in the dextrocardiac twin it is longer (30 ms) than in his cotwin (25 ms). As regards the echocardiographic and dynamic ECG examination, normal data were obtained for both twins which were pratically superposable to those obtained three years before.

A case of 15-years old, Roman male twins affected by balanic hypospadia is reported. Previous corrective surgery had not been satisfactory, leaving both boys with a curvature of the last portion of the penis. Urographic examination, carried out upon presentation, revealed in both patients a mirror renal ectopy with fusion of the two kidneys. In both, the displaced malformed kidney is below the normally situated one. In depth examination shows: 1) that the malformation concerns not only external genitals but also internal urogenital organs because of the monolateral ectopy of the normal kidney and the malformation of the ectopic kidney in both twins; 2) that the twins are MZ and that their teratological specularity is biologically of interest.

Specularity, or mirror imaging, is a well known phenomenon in twins, particularly MZ twins. It may involve slight forms, such as handedness, or rare forms, such as those involving single organs, like the heart, which can be on the left side in one twin and on the right in the MZ cotwin. That must occur in the early embryogenetic stages, and various environmental and genetic factors may be involved. In particular, one can speculate that genetic variations in cell-adhesion molecules (CAM) and/or the late time of splitting of the conceptus to originate the two twins, may all play a role.

A case of double bilateral renal vessels in both twins of a MZ pair is reported for the first time. Even in non-twins, the anomalies reported so far involved the inferior polar arteries in agreement with the embryological development. The two male twins, examined at the age of 14 years, had simultaneously developed a marked hypertension at the age of 7 years. Zygosity was determined by blood group and HLA analysis and various clinical tests were carried out to diagnose the condition. It is suggested that the anomaly is the result of a genetically induced early block in embryonic development.

A male twin pair, the result of 34 weeks gestation by dates, 38 weeks by estimation, was delivered at our hospital by normal vaginal delivery on 02.01.87.

The mother is a 27-year old, A,Rh+ healthy school teacher. She was married to her 33-year old, first-degree cousin in 1981. They have no family history of malformed newborns or other inherited diseases.

The first pregnancy of this gravida-four mother was in 1982 and resulted in a full-term, healthy female weighing 3.5 kg. The second pregnancy was in 1984 and resulted in a 36-weeks, alive female with occipital encephalocele, who died 12 hr after birth. It is not known if this newborn had other accompanying congenital anomalies. The third pregnancy was in 1985, and the fetus was aborted at 12 weeks gestation because of anencephaly, which was diagnosed by ultrasound.

The last pregnancy was followed at a private clinic without doing ultrasound. It was not complicated by any illness, drag intake, or X-ray exposure.

After 34 weeks of gestation, male twins were delivered by spontaneous vaginal delivery. Each one had his own placenta and umbilical cord. The first twin was a healthy male weighing 2.4 kg, with Apgar score 7/8, who was discharged home in a good general condition, and was doing well when he was seen at follow up one month later.

The second twin was a male weighing 2.15 kg, and having a length of 48 cm. We was microcephalic with a head circumference of 28 cm.