Present attempts to identify genes contributing to coronary heart disease (CHD) risk focus on “candidate genes”. With respect to CHD this could be any gene whose protein product is directly or indirectly involved in atherogenesis, thrombogenesis or thrombolysis/fibrinolysis. Genes that exhibit associations with absolute risk factor levels may be referred to as “level genes” to distinguish them from “variability genes”, which are genes involved in establishing the framework within which environmental influences may cause risk factor variation. In a series of persons recruited from the Norwegian Twin Panel, confirmatory evidence for level gene effect with respect to apolipoprotein B (apoB) concentration was found with an XbaI polymorphism in DNA at the apoB locus corresponding to residue 2,488 in the mature protein. Evidence for variability gene effect with respect to apoB as well as body mass index emerged with DNA variants in the 3′ part of the apoB gene. Level gene effect with respect to apolipoprotein A-I (apoA-I) and high density lipoprotein (HDL) cholesterol as well as apparent variability gene effect with respect to total and LDL cholesterol were detected with a DNA polymorphism at the cholesteryl ester transfer protein (CETP) locus. The first example of interaction between normal genes in determining risk factor level was uncovered in analysis of the apolipoprotein E (apoE) polymorphism and a restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus. An LDLR gene identified by presence of a PvuII restriction site eliminated completely the well known effect of the apoE4 allele on cholesterol level. Finally, in families where high Lp(a) lipoprotein level (a well established risk factor for CHD) segregated as a Mendelian trait, very close linkage with an RFLP at the plasminogen locus was established and DNA variation at the LPA locus reflecting varying numbers of a structure homologous to the “kringle IV” region of plasminogen was uncovered.

Despite increasing scientific evidence for a causal role of tobacco smoking in lung cancer and coronary heart disease, an alternative hypothesis was put forward several decades ago. The constitutional hypothesis has stated that there are genetic or other common factors, which predispose both to smoking and disease. A critical test of this hypothesis was considered the pattern of occurrence of disease in monozygotic (MZ) twin pairs in which one is a smoker and the other never has been a smoker. Initial twin studies found only small differences in the mortality of smoking and nonsmoking twins of discordant pairs. In the Finnish Twin Cohort, a population-based panel of adult like-sexed twin pairs, a questionnaire study carried out in 1975 permitted identification of 2488 twin pairs discordant for cigarette smoking. Analyses of total mortality and mortality due to coronary heart disease and lung cancer indicate that the smoking members of discordant MZ pairs are at higher risk than their nonsmoking cotwins; increased mortality of smoking cotwins was also found on 21-year follow-up of smoking-discordant pairs in Sweden. Incidence data and noninvasive studies of atherosclerosis in the Finnish sample provide confirmatory evidence for the causal role of smoking in the etiology of coronary heart disease and lung cancer.

A birth-record based Registry is nearing completion of some 8,000 pairs of twins born in Minnesota from 1936 to 1955, plus some 1,200 pairs of male twins born 1971-81. The middle-aged twins were recruited with graded incentives so that ease of recruitment could be measured; it was found that pairs concordant for ease of recruitment were no more similar than discordant pairs in education, socioeconomic status (SES), or a variety of personality and interest factors, ie, that selection bias may not be a problem in research with adult twins when contacts are only by mail. A 50% decrease in neonatal mortality from 1936-55 to 1971-81 was associated with an increase from 3.5 to 4.0 per thousand in the frequency of viable MZ twin births. The broad heritability of SES, educational attainment, fecundity, and risk for divorce ranges from 0.30 to 0.50, although all 4 variables are plainly multifactorial and the latter 2 both involve variance contributed by a second person. Investigators interested in making use of this research resource are invited to submit proposals.

The biases in volutary participation by adult twins are well known but less attention has been paid to twin children where parents decide on participation and provide much of the information. Several aspects of reporting including the assessment of zygosity are compared in four large Australian data bases: 1) a nationwide compulsory (and hence representative) survey of literacy and numeracy; 2) a nationwide “Twins in School” survey of parents and teachers of twins run through Education Departments and AMBA, the parents organisation in conjunction with LaTrobe; 3) the LaTrobe Twin Study which is a longitudinal program involving frequent interactions between families and researchers, and 4) the Australian NHMRC Twin Registry which has surveyed a large sample of their families with twin children by mail. One potential bias comes when recruitment is on a continuing basis as in the LaTrobe Twin Study and the Australian Twin Registry when differences between “early” and “late” enrolling families arise. One difference between the four samples arose from parents being much more likely to contrast their twins and to report problems in one but not the other, whereas teachers' and psychologists' assessments of these same children generally reported much smaller intrapair differences. Future studies should have some common questions to provide comparative data on such biases. Key questions are proposed for this area, mainly on the perceived need for different forms of remediation, together with other recommendations about the minimal essential baseline data set for a registry.

Despite some evidence that genotype-environment interaction (G×E) effects may be involved in the variation observed in behavioral and biological traits, few attempts have been made to detect and quantify this component of genetic variation in humans. We propose that one way to achieve this goal is to challenge several genotypes in a similar manner, submitting both members of several MZ twin pairs to an ethically acceptable experimental treatment capable of inducing an adaptative response. In this situation, the G×E effect can be assessed with a two-way analysis of variance for repeated measures on one factor, the treatment effect. In this design, twins are considered nested within the pair, whereas the treatment effect is considered a fixed variable. The intrapair resemblance in the response to the treatment is quantified with an intraclass correlation coefficient computed with between-sibhips and within-sibhips means of squares. To illustrate this approach, changes induced by long-term endurance training were studied in 10 MZ twin pairs. Significant intrapair resemblance in the response of maximal oxygen uptake was observed, with about 7 to 8 times more variance between pairs than within pairs. This design with MZ twins may be helpful in the study of human variation for multifactorial phenotypes.

This study examines the heritability of cigarette smoking, alcohol, and coffee consumption in 4,960 adult, male twin pairs (2,390 MZ and 2,570 DZ pairs) participants in an epidemiologic survey of the NAS-NRC Twin Registry conducted in the USA during 1972-73. Heritability estimates for smoking, alcohol and coffee use were calculated both before and after adjustment for shared variance between these behaviors and other demographic characteristics including socioeconomic status and an occupational adjustment score. The objective of the analysis was to determine the impact of adjustment for covariates on heritability estimates of smoking, alcohol and coffee use. Before adjustment, genetic effects in smoking, alcohol and coffee use accounted for 53%, 36%, and 45% of the variance, respectively. After adjustment, the corresponding estimates were 35%, 29%, and 36%. The fact that these estimates remained significant after adjustment for covariates leads to increased confidence about the role of genetic factors in substance use behaviors.

In order to examine the chronological changes in genetic variance and heritability of arterial systolic and diastolic blood pressure (SBP and DBP) of Chinese infants in Taiwan, a total of 339 same-sexed twin neonates born in four major general teaching hospitals in Taipei City were studied. Based on placentation and 12 red blood cell antigens, 274 monozygotic (MZ) and 65 dizygotic (DZ) twin pairs were identified and followed up to the age of one year. Both SBP and DBP were measured by Doppler blood pressure monitor. Within-pair mean squares of SBP and DBP were consistently smaller in MZ than DZ twins at ages one month and over. The findings remained unchanged after the adjustment for the effects of age, sex, gestational age, placentation and physical state during blood pressure measurement. Falconer's heritability indices for adjusted SBP and DBP at ages two months and over ranged from 0.29 to 0.55 and from 0.27 to 0.45, respectively. The study indicates an important genetic influence on blood pressure during infancy.

Subjects were 189 twin pairs, 165 MZ and 24 same-sexed DZ, who entered the junior high school affiliated to Tokyo University (sample T), and 93 twin pairs, 71 MZ and 22 same-sexed DZ, who were registered at Kinki University (sample K). The zygosity was previously identified by many genetic markers, and this study aimed at zygosity diagnosis by questionnaire. The latter included three questions: “How are you alike?”, “How often are you mistaken?”, and “By whom are you mistaken?”. According to the degree, 1-3 points, 1-3 points, and 1-4 points were given for each question, and the sum of the points of each pair of twins was calculated. Zygosity was determined by the sum of points, distributed from 6 to 20. Namely, if the sum was 6-13, the twin pair was considered MZ, and if the sum was 14-20, DZ. More than 90% of twins were diagnosed correctly by use of this cutting point. This result was in accordance with that obtained by use of discriminant function analysis. It is concluded that zygosity diagnosis by questionnaire is convenient and useful, in particular for epidemiological research.

The present study deals with the relationship between blood uric acid level and human behavior. Subjects were 37 MZ and 7 DZ twins aged from 18 to 45 years. In males, blood uric acid level increased with age, while it decreased with age in females. Blood uric acid level was corrected and standardized using regression lines separately for males and females. The distribution of standardized uric acid level corresponded well with the theoretical curve of normal distribution. The intraclass correlation coefficient for standardized uric acid level was r = 0.370 (P < 0.05) for the 37 MZ twins, but not significant for the 7 DZ twins. These findings suggest that blood uric acid level is genetically controlled. By the analysis of 12 personality traits in YG (Yatabe-Guilford) character test, it was revealed that “General activity” was more controlled by genetically than environmentally. In the evaluation of the correlation between standardized uric acid level and the YG 12 personality traits, significant correlation was observed in “Lack of agreeableness” and “Rhathymia”. Since these two personality traits include the factor of “activity”, it is concluded that the plasma uric acid level and activity in a broader sense are under genetic control. This conclusion is consistent with the generally accepted view that persons with high uric acid level are more active and energetic than those with low level.

In order to examine the genetic variance and heritability of serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides, a total of 349 pairs of same-sexed twin neonates born in four major general teaching hospitals in Taipei City were studied. Based on the placental pattern and 12 red blood cell antigens, 271 monozygotic (MZ) and 78 dizygotic (DZ) twin pairs were identified. There was a significant genetic variance for total cholesterol, HDL-C, LDL-C, and triglycerides both unadjusted and adjusted for sex, gestational age and placentation. The unadjusted heritability of total cholesterol, HDL-C, LDL-C, and triglycerides was 0.59, 0.30, 0.25 and 0.75, respectively; while the corresponding adjusted heritability was 0.74, 0.38, 0.31, and 0.49, respectively. Intrapair variance of serum lipids was not significantly different between monochorionic and dichorionic MZ twins.

The Finnish Twin Cohort material was used to estimate genetic and environmental effects in the etiology of hyperopia (farsightedness). All twin pairs in the cohort born before year 1927 (age 60 years and over at the time of the study), with both members alive, were sent a questionnaire. The questionnaire included questions of past and present eye diseases, visits to ophthalmologists, use of glasses and other vision-related questions. The hyperopia was assessed by asking the patients to send their last prescription for glasses to the authors. Twins with any eye disease affecting refraction (cataract, corneal damage), operation or trauma to their eyes were discarded from the present study. In 191 pairs (80 monozygotic and 111 dizygotic pairs) one or both members of the pair had a hyperopic refractive error. The correlations of refraction between right and left eyes of both MZ and DZ pairs were high (Spearman Rank Correlations of 0.86-0.89). The intrapair correlations among MZ pairs were higher (0.44 for right and 0.45 for left eyes) than intrapair correlations among DZ pairs (0.24 for right and 0.15 for left eyes). The variances were not significantly different among MZ and DZ pairs. The classical analysis of heritability gave an estimate of 0.75 for hyperopia. The result suggests that genetic factors are important in hyperopia and especially in hyperopia of higher degree.