For epidemiological purposes, it is customary to assume that same-sex (SS) dizygotic (DZ) twin pairs are approximately equal in number to unlike-sex (OS)-DZs, the remainder of the SS pairs being monozygotic (MZ). It is also customary to consider OS-DZs to be epidemiologically representative of all DZs, which can only mean that difference in frequency of any trait between OS and SS twins is due to the MZ fraction of the SS twins. Since this is assumed as a premise, there is little value in its usual appearance as the result. The basic tenet of twin biology, that most twin excess anomalies are due to MZs, is a myth self-perpetuated by a methodological tautology, and is false, at least for mortality. In a consecutively ascertained and prospectively studied sample of 616 twin pairs, over 80% diagnosed for zygosity, it can be shown that the standard assumption mentioned above have given impossible answers. The most probable possible answer is that mortality does not differ greatly with zygosity overall, but that SSDZ mortality is much higher than that of OS twins, and probably even higher than that of MZs. Race differences in the probable answers further suggest that standard assumptions of the Weinberg method may have consistently provided false explanations for race differences in the OS fraction of twin pairs.

The good result of this congress (the fifth of the series), in terms of quality of papers and number of participants, proves we were on the right track when in 1974 we founded the International Society for Twin Studies, and even more proves that the interest in gemellology is increasing.

I wish to thank our many colleagues who contributed to the promotion, construction and success of this field of biomedical research, and particularly Gordon Allen, Ian MacGillivray, Walter Nance, Paolo Parisi, and of course Aldur Eriksson.

For my part, I would like to emphasize that going from the title “Study of Twins” given to my book in 1951 to the word gemellology placed in the title of our quarterly Acta Geneticae Medicae et Gemellologiae in 1952, I wanted to affirm: first, that the study of twins is a branch of modern genetics; second, that the study of twins represents a “logos,” that is, a subject composed of acquired concepts, of constant phenomena and specific methods of research on twins in normality, in pathology and in population. With this word, now also adopted by Professor Nance in his Presidential Address, “Introduction to Gemellology,” twin research has become an identified field of science.

In order that the Amsterdam Congress may be as fruitful as the previous ones, I believe it useful to look out of the window of the future with you to see some roads which could be new frontiers of gemellology.

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.

Using symbols from population biology, a continuum of reproductive strategies can be distinguished ranging from r, the production of large numbers of offspring provided with minimal care, to K, the production of few offspring nurtured intensively. While all humans are at the K end of the continuum, some are proposed to be more so than others. If multiple egg production is part of an r-reproductive strategy, certain facts may be ordered. Compared to mothers of singletons, for example, mothers of DZ twins nave a lower age of menarche, a shorter menstrual cycle, a higher number of marriages, a higher rate of coitus, more illegitimate children, a closer spacing of births, a greater fecundity, more wasted pregnancies, a larger family, an earlier menopause, and an earlier mortality. Further, all twins have a shorter gestation period, a lower birth weight, and a greater incidence of infant mortality, with DZ twins having a greater frequency of health disorders, a higher mortality rate, and a lower rate of enrollment in volunteer registries. Multiple birthing also occurs more frequently in families of lower than of higher social status, and in those of African than of European and especially than of Orientai descent.

We consider a study of MZ and DZ twin pairs ascertained because one or both twins have a disease. Genotypes at a major locus are known and putative environmental risk factors have been measured for all individuals. The power of the study to estimate the effect on liability of the measured and residual genetic and environmental effects (Gm, Gr, Em, Er) and all two-way interactions between them (except Gr × Er) is estimated by simulation. If liabilities can be indexed on a continuous scale (eg, blood pressure as an index of liability to hypertension), then a study of 600 MZ and 600 DZ pairs would have sufficient power to detect quite subtle interaction effects, even if ascertainment is greatly biased toward MZ twins. If liabilities cannot be measured and only affection status is known, then the power of the study would be much lower, although not impracticably so. There appears to be no advantage in augmenting the twins with a sample of control individuals who have been drawn at random from the population regardless of disease status, at least for the case we have considered in which the disease threshold on the liability scale is assumed to be known without error. The argument is developed in terms of the utility of the design for research into breast cancer.

A new method is described for plotting the growth in mental development from birth to adolescence. Using data from a large sample of twins followed since birth, a dimension of mental growth was constructed by arraying all tests in order of difficulty, then computing the average gain from age to age. The gain was expressed in standard-deviation units, which reflected the upward shift in the score distribution from time X to time X + 1. When cumulated over ages, the scores generated a mental growth curve for the sample as a whole, as well as for each case individually. The curves displayed a very rapid gain in mental growth over the first 24 months of life, with the complexity of mental functions advancing by nearly 20 standard deviations from birth to two years. Thereafter the gain progressively tapered off until reaching a final increment of 0.5 SD gain between 15 years and adulthood. At this point, the terminal level of mental growth reached an average value of 31 SD units, with a spread of individual differences equal to ± 3 SD units. The scores at each age represented a combination of base level plus gain from the preceding age, and during infancy the gain scores were large in relation to base. At later ages, however, the gain scores were comparatively small, both in absolute terms and in relation to base. These characteristics help explain the typical low-order correlations obtained among mental test scores during infancy, vs the progressively larger correlations obtained at later ages.

Advances in computer technology have made possible a greater sophistication in the statistical analysis of pedigree data, however this is not necessarily manifest by fitting more comprehensive causative models. Planned twin and family studies measure numerous explanatory variables, including perhaps genetic and DNA marker information status on all pedigree members, and the cohabitation of all pairs of individuals. A statistical analysis should examine the contribution of these measured factors on individual means, and in explaining the variation and covariation between individuals, concurrently with the postulated effect of unmeasured factors such as polygenes. We present two models that meet this requirement: the Multivariate Normal Model for Pedigree Analysis for quantitative traits, and a Log-Linear Model for Binary Pedigree Data. For both models, important issues are examination of fit, detection of outlier pedigrees and outlier individuals, and critical examination of the model assumptions. Procedures for fulfilling these needs and examples of modelling are discussed.

In the Louisville Twin Study, pairs of 3- and 4-year-old twins were provided with standardized competitive or cooperative tasks in a laboratory setting. Some tasks required a pair of twins to share toys; other fostered a more competitive engagement between the twins. Behavioral ratings identified temperament and social components at both ages, and between the two ages, there were transformations in the links between the components. Parental ratings of the twins' temperament at the same ages were moderately correlated with the laboratory observations, but the pattern of the relations changed from one age to the next. The combined sets of measures were subjected to twin analyses for 43 pairs of twins. The results are discussed in terms of the similarity of MZ and DZ pairs for the dimensions of temperament and the transformations of temperament.

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.

Linear regression models are used to explain the variations in the twinning rates. Data sets from different countries are analysed and maternal age, parity and marital status are the main regressors. The model building technique is also used in order to study the secular decline in the twinning rate. Linear regression technique makes it possible to compare the effect of different factors but the method requires sufficiently disaggregated data.

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.

Detailed twin birth rates for the United States are unavailable since 1964. In 1983 the crude twinning rate for women of white race was higher than in 1964, but there had been great changes in maternal age and parity. Indirect standardization for maternal age and birth order provides estimated total twinning rates that can be compared over the entire period. The adjusted rates for whites show a nearly continuous increase except after a 2-year reporting hiatus, 1969-70, when rates dropped back 10%. In blacks the adjusted rate increased between 1966 and 1978, except for the 1968-71 shift. The distributions of rate increases by maternal age and by race argue against effects of medical ovulation stimulants, but a disproportionate increase of triplets argues for such effects. Study is needed of rates specific for maternal age and parity, rather than of total rates.

When the univariate twin design is extended by including parents of twins, it is possible to assess additive genetic effects in the presence of assortative mating and genotype-environment correlation, the effects of parental influence, as well as the extent of residual shared environmental influences. The analysis of data obtained in such an extended twin design can be carried out by means of constrained maximum likelihood confirmatory factor analysis. Specifically, the structural model underlying this design can be represented as a LISREL model with nonlinear constraints. This representation offers the possibility to consider extended multivariate twin designs involving common genetic and environmental factors. The proposed method will be illustrated with applications to simulated and real data.

The changing influence of genetic factors of temperamental individuality has been studied longitudinally in a group of 44 same-sexed twin pairs at four different ages from infancy to puberty. Previous results showed that genetic factors seemed to play an important role in the development of temperamental characteristics when the twins were in infancy and at six years of age. The present report shows that when the within-pair differences in temperament are studied again at age 15 years, the similarity of identical pairs is even higher than at earlier ages. When shared and nonshared stress in the twin pairs was assessed at this age, some interactions were found between within-pair differences in temperament, stress and zygosity.

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.

The effects on twin data of social interaction between spouses is examined. When social interaction leads to an increase in marital resemblance (eg through reciprocal imitation), the variance of married individuals is increased, compared to the variance of unmarried individuals. Furthermore, the expected correlations between concordant married twin pairs will be lower than the expected correlations between concordant unmarried twin pairs, with the discordant twin correlations being intermediate in value. It is therefore possible, in principle, to detect the effects of marital interaction without using either longitudinal data or data on spouse pairs. However, to be detectable in twin data, marital interaction must be strong, or must exhibit marked asymmetry of effects between males and females. Genotype × environment interaction can also produce heterogeneity of correlation between concordant married, discordant, and concordant unmarried twin pairs, when genetic and environmental effects interact with marital status. However, this will usually produce increased estimates of the genetic component of variance in unmarried twins, whereas marital interaction produces increased genetic variance in married twins.

A model of nature-nurture interaction in school situations emanating from a longitudinal Swedish twin project is presented. This model implies that interactional effects measured by MZ-DZ within-pair comparisons over time are related to the type of behavior studied, as well as teacher and pupil influences at different levels. In a more permissive and stimulating school situation, hereditary factors are hypothesized to be more influential (decisive for behavioral variation) than in a more restrictive and nonstimulating situation. A study of such interactional effects will require longitudinal measurements of pupil behavior as well as teacher and parental influences. To acquire a variation in permissiveness/restrictiveness and stimulation/nonstimulation at the societal level, comparisons are made between twins attending grade 4-6 in compulsory schools in Sweden and twins of the same age attending Israelian Kibbutz schools.

The twinning rate remained nearly Constant up to 1968, then decreased in 1974 and gradually increased with the year. The triplet birth rate remained nearly Constant up to 1974, then increased up to 1982, where the rate was 1.8 times higher than in 1968, and decreased thereafter. On the other hand, the quadruplet birth rate remained nearly Constant up to 1968, was eightfold in 1975, then decreased until 1984 and suddenly increased to 8 per million births in 1985. The higher multiple birth rates since 1974 was attributed to the higher proportion of mothers treated with ovulation-inducing hormones in Japan. The stillbirth rates decreased to 2/5 for male twins and to 1/3 for female twins during the 25-year period from 1960, to 2/5 for triplets and to 1/5 for quadruplets during the 34-year period from 1951.