We analyze the association between the rates of multiple maternities. Correlation analysis is suitable if there are at least monotonic relationships between the variables. A decreasing tendency can be observed in the rates of multiple maternities in Sweden and in its 25 counties for the period 1751–1960 and the effect of external variables can be assumed to be monotonic. After 1960, the rates of multiple maternities show marked increases, mainly caused by ovulation stimulants and the introduction of other artificial reproduction techniques. We transformed the triplet and quadruplet rates according to Hellin's law in order to obtain rates on the same scale as the twinning rate. The time trends for the multiple maternities in Sweden as a whole were quite similar. The regional differences in the twinning rates could not be satisfactorily explained by maternal age. Alternative attempts to eliminate the effect of other time-dependent factors were to study partial correlation coefficients when the time was kept fixed and the correlation coefficients based on cross-sectional regional data. Both the ordinary and the partial correlation coefficients showed strong regional variation. Cross-sectional analyses gave correlation coefficients similar to the partial correlation coefficients for Sweden as a whole. The variations in the correlation coefficients between the twinning and the triplet rates seem to be caused by other time-dependent factors and the effects of these factors show strong regional variation. After elimination of such factors, the correlation between the twinning and the triplet rates is moderate.

Every statistical model is based on explicitly or implicitly formulated assumptions. In this study we address new techniques of calculation of variances and confidence intervals, analyse some statistical methods applied to modelling twinning rates, and investigate whether the improvements give more reliable results. For an observed relative frequency, the commonly used variance formula holds exactly with the assumptions that the repetitions are independent and that the probability of success is constant. The probability of a twin maternity depends not only on genetic predisposition, but also on several demographic factors, particularly ethnicity, maternal age and parity. Therefore, the assumption of constancy is questionable. The effect of grouping on the analysis of regression models for twinning rates is also considered. Our results indicate that grouping influences the efficiency of the estimates but not the estimates themselves. Recently, confidence intervals for proportions of low-incidence events have been a target for revived interest and we present the new alternatives. These confidence intervals are slightly wider and their midpoints do not coincide with the maximum-likelihood estimate of the twinning rate, but their actual coverage is closer to the nominal one than the coverage of the traditional confidence interval. In general, our findings indicate that the traditional methods are mainly satisfactorily robust and give reliable results. However, we propose that new formulae for the confidence intervals should be used. Our results are applied to twin-maternity data from Finland and Denmark.

This paper examines why parents of twins or adult twins themselves request zygosity testing. Of 405 multiples including 8 sets of triplets, the majority (93%) were monozygotic. Age of testing ranged from 0 days to 73 years. About 50% of requests came from parents or twins who were curious about, or expressed a need to be certain of, their zygosity. Other reasons included health concerns (current or future), other twins in the family, and misinformation about zygosity, frequently because of the erroneous assumption that all dichorionic twins are dizygotic. Parents of monozygotic twins may expect their twins to be ‘identical’ and believe their twins to be dizygotic because of minor phenotypic differences between them. Dizygotic twins like other siblings may share a phenotypic resemblance. Health professionals should be aware that zygosity of multiples may not always be obvious to parents and that accurate knowledge of zygosity may be justified.

Maternal infection with parvovirus B19 during pregnancy can cause aplastic anemia in the fetus. Severe anemia may lead to nonimmune hydrops or fetal demise. In the case reported, the demise of one twin was diagnosed by ultrasonography in an asymptomatic 21-year-old para 1-0-2-1 African American at the gestational age of 25 weeks. The deceased twin (A) was grossly hydropic with anasarca, ascites, pleural and pericardial effusions, and a thickened placenta. Parvovirus B19 DNA was found in the amniotic fluid of Twin A using the polymerase chain-reaction technique. Serial scans of Twin B showed normal growth and no evidence of hydrops. The pregnancy was managed expectantly until 29 weeks when delivery was indicated by maternal disseminated intravascular coagulation. Maternal IgM antiparvovirus B19 antibodies were detected at the time of delivery. Antiparvovirus B19 IgM antibodies were not present in Twin B. These serologic studies suggest a recent acute maternal infection and refute such an infection in Twin B. We present a case of differential transmission of parvovirus B19 in a twin pregnancy with in utero death of the infected twin and subsequent maternal disseminated intravascular coagulation.

Studies indicate that low birthweight (LBW) children display reduced deciduous tooth size but there is little information about permanent tooth size. It has also been shown that dental fluctuating asymmetry (FA) increases in response to various environmental influences, but the relationship between birthweight and FA remains unclear. The aim of this study was to compare tooth size and asymmetry, according to birthweight, in the deciduous and permanent dentitions of a sample of Australian twins. The study sample comprised 436 twins, classified into 2 groups: normal birthweight (NBW > 2500g) and low birthweight (LBW ≤ 2500g). For each individual it was generally possible to measure maximum mesiodistal crown diameters of both deciduous and permanent central incisors from serial dental models. Correlations were calculated between tooth-size variables and birthweight; subsequently comparisons of tooth size and FA were made between the LBW and NBW samples using Student's t tests. Small positive correlations (around .1) were noted between birthweight and tooth-size variables. There was no evidence of tooth-size reduction in the LBW male sample, but the LBW females displayed tooth-size reduction of approximately 2–3% for both deciduous and permanent incisors, compared to the NBW females. There was no evidence of increased FA in the LBW individuals of either sex. These findings indicate that developing teeth are generally well-protected from developmental disturbances during prenatal and perinatal periods. Further research is needed to clarify the biological basis of an apparently true but weak association between tooth size and birthweight.

Weight discordance is very rare in monozygotic (MZ) twin pairs; when found, however, such pairs are advantageous in the search for either environmental or epigenetic causes and consequences of obesity. We analyzed the growth patterns of young adult MZ pairs discordant and concordant for obesity. Screening 5 consecutive birth cohorts (1975–1979) of 22- to 27-year-old Finnish twins (the FinnTwin16 study), we found 14 obesity discordant (Body Mass Index [BMI] difference ≥ 4 kg/m2) MZ pairs out of 658. Ten pairs participated in clinical studies. Nine concordant pairs (BMI difference ≤ 2 kg/m2) were examined as controls. Lifetime measured heights and weights recorded in hospitals and health centers were traced manually. Height development was similar in all the co-twins of both groups. The weight differences between the co-twins of the discordant pairs began to emerge at 18 years leading to an average discordance of 16.4 kg, 5.6 kg/m2(p for both = .005) at 25.7 years. The heavier co-twin weighed 221 g (p = .066), 1.0 kg/m2 (p = .01) more already at birth than the leaner, but the differences waned by 6 months of age and reappeared only after adolescence. Both the leaner and the heavier co-twins of the discordant pairs weighed more than expected by the singleton reference values (Cole et al., 1998) after 8 years. The concordant co-twins, on the other hand, grew similarly and after 6 months, their mean growth was not distinguishable from the singleton patterns. Young adulthood represents a critical period of gaining weight irrespective of genetic background in this twin sample.

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.

This article describes a pharmacogenetic investigation of nicotine metabolism in twins. One hundred and thirty-nine twin pairs (110 monozygotic and 29 dizygotic) were recruited and assessed for smoking status, zygosity, and health conditions known or suspected to affect drug metabolism. Participants underwent a 30-minute infusion of stable isotope-labeled nicotine and its major metabolite, cotinine, followed by an 8-hour in-hospital stay. Blood and urine samples were taken at regular intervals for analysis of nicotine, cotinine, and metabolites by gas chromatography–mass spectrometry or liquid chromatography–mass spectrometry and subsequent characterization of pharmacokinetic phenotypes. DNA was genotyped to confirm zygosity and for variation in the primary gene involved in nicotine metabolism, CYP2A6. Univariate and multivariate biometric analyses planned for the future will determine genetic and environmental influences on each pharmacokinetic measure individually and in combination with each other, and in the presence and absence of covariates, including measured genotype. When the analyses are completed, this study will result in a more complete characterization of the impact of genetic and environmental influences on nicotine and cotinine metabolic pathways than has heretofore been reported. The approach taken, with its use of a quantitative model of nicotine metabolism, highly refined metabolic phenotypes, measured genotype, and advanced tools for biometric genetic analysis, provides a model for the use of twins in next-generation studies of complex drug-metabolism phenotypes.

Monozygotic (MZ) twins spend more time with each other and are more genetically alike than are dizygotic (DZ) twins or nontwin siblings and therefore probably experience less diversity in their playmates than DZ twins, who in turn may experience less diversity than other-age siblings. Thus MZ twins may be more inhibited than DZ twins, who may in turn be more inhibited than nontwin siblings. To test this, 205 children (42 MZ twins, 94 DZ twins, and 69 nontwin siblings) were assessed in a playroom laboratory during free play with an unfamiliar peer. Children's inhibition was rated based on latency to touch a toy for the first time and amount of time spent interacting with the other child. Additionally, the Child Behavior Checklist (CBCL) withdrawn scale was used to assess inhibition according to parent report. Behavioral ratings showed that MZ and DZ twins did not significantly differ on the inhibition or withdrawn ratings. DZ twins were significantly more inhibited than were nontwin siblings, according to laboratory ratings. Greater inhibition of twins during the free peer play situation can be explained by their relative lack of experience in playing with children who are less genetically and phenotypically like themselves. Parental ratings showed exactly the opposite pattern, suggesting a rater bias effect.

The gender diagnosticity (GD) approach of Lippa (1995) was used to evaluate the relationship of within-sex differences in psychological masculinity–femininity to a genetic characteristic, the length of a repeated CAG sequence in the X-linked androgen receptor (AR) gene. Previously assessed adult samples in Australia and Sweden were used for this purpose. A weak relationship (correlations in the range .11 to .14) was obtained in both countries. Additional data from adolescent twins from Australia (12-, 14-, 16-year-olds) did not confirm such a relationship at those ages, especially for males. The fact that this sample consisted of twins permitted two kinds of within-pair comparisons: (1) Did the dizygotic twin who had the longer AR sequence have the higher GD score? (2) Was one twin's GD score more highly correlated with the other twin's AR score in MZ than in DZ pairs? The answer in both cases was negative. Clarification of these relationships will require large samples and measurements at additional ages.

In this study we examined the genetic and environmental structure of four dimensions from Cloninger's personality system: novelty-seeking (NS), harm-avoidance (HA), reward-dependence (RD), and persistence (PS). Although adult twin studies suggest that these personality dimensions are moderately heritable, this is the first twin study of Cloninger's personality dimensions in adolescence — a period marked by significant physiological and social changes. Study participants included 1851 adolescent twins between the ages of 11 and 18 years; 878 complete twin pairs and 95 singleton-responding twins. Subjects were participants in two community-based samples of twins residing in the state of Colorado. Results indicated that cross-sectional mean levels for NS, HA and RD tended to show modest increases across the adolescent years, while PS showed modest mean decreases. Consistent sex differences in means were found only for RD. Univariate biometrical twin models were used to decompose trait variance into genetic and environmental sources. Results indicated that for NS, HA and RD additive genetic influences and unique environmental effects were sufficient to explain the data. PS, however, could be explained by unique and common environmental effects only, with different patterns of common environmental effects for males and females. We found moderate heritability estimates for NS, HA and RD ranging from .28 to .36 — with no evidence for sex-limitation in those influences.

Amulticategory item-response theory model was developed to characterize developmental changes in three items relating to the assessment of puberty in adolescent twin girls and boys. The model allowed for the fixed effects of age on probability of endorsing the responses and for the random effects of individual differences on the timing of pubertal changes relative to chronological age. In girls, the model was applied three-wave data on twin pairs (N = 414 female monozygotic [MZ] and 197 female dizygotic [DZ] pairs) and female twins from boy–girl pairs (N = 300 twins) from the Virginia Twin Study of Adolescent Behavioral Development. In boys, the data comprised 318 MZ and 185 DZ pairs and 297 male twins from boy–girl pairs. A total of 3172 and 2790 individual twin assessments were available in girls and boys, respectively, spanning ages 8–17 years. The availability of twin data allows the contributions of genes, the shared environment and individual unique environmental experiences to be resolved in the relative timing of pubertal changes. Parameters of the mixed model including fixed effects of age and random effects of genes and environment were estimated by Markov Chain Monte Carlo simulations using the BUGS algorithm for Gibbs sampling. The estimated standard deviation of random differences in the timing of puberty relative to age was 0.96 years in girls and 1.01 years in boys. The estimated intraclass correlations for the relative timing of pubertal changes were 0.99 +/−0.01 in MZ girls, 0.52 +/−0.02 in DZ girls, 0.88 +/−0.04 in MZ boys and 0.44+/−0.02 in DZ boys, indicating a very large contribution of genetic factors to the relative timing of pubertal change in both sexes. Additive genetic factors account for an estimated 96.3+/−3.3% of the total variance in random effects in girls and 88.0+/−3.6% in boys. Shared environmental influences account for 3.6+/−3.4% in girls and 0% in boys. In girls, nonshared environmental effects explain 0.1+/−0.1% of the total residual variance. The comparable figure in boys is 12.0+/−;3.6%.

We compared the accuracy of genotyping for DNA extracted from lymphocytes to that of DNA amplified from buccal epithelial cells. Amplification was via a rolling circle/φ29 DNA polymerase commercial kit. Paired buccal and lymphocyte DNA samples were available from 30 individuals. All samples were genotyped for 12 SNPs, 5 microsatellites and 2 VNTRs. The accuracy of genotyping (no-call proportions, reproducibility, and concordance) was similar for DNA from lymphocytes in comparison to amplified DNA from buccal samples. If used with caution, these data suggest that rolling-circle whole-genome amplification can be used to increase the DNA mass available for large-scale genotyping projects based on DNA from buccal cells.

Nonresponse occurs when individuals either have no chance of being included in a study (noncoverage), refuse to take part (unit nonresponse), or fail to give complete information (item nonresponse). The purpose of this article is to test the possible biasing effects of nonresponse on the results of behavioral-genetic studies. Simulations and a real data ‘natural’ experiment were used to determine the impact of nonresponse on estimates of additive genetic and environmental effects. The simulations used realistic twin-pair correlations and models of nonresponse derived from prior research. The real data ‘natural experiment’ used data from a nationally representative birth-cohort twin study (E-Risk Study) and compared model results from families who had responded to a mail survey to those from all study cases. Results showed that the primary influence of nonresponse was to attenuate the effect of the shared environment and to inflate estimates of non-shared environment and additive genetic effects. At high levels of nonresponse a spurious nonadditive genetic effect (suggesting genetic dominance) was also found. Study nonresponse was shown to have the potential to bias the findings of behavioral-genetic research. Design and analysis methods that can be used to alleviate this potentially important biasing effect in behavioral-genetic studies are discussed in light of these findings.

Statistical power of the classical twin design was revisited. The approximate sampling variances of a least-squares estimate of the heritability in a univariate analysis and estimate of the genetic correlation coefficient in a bivariate analysis were derived analytically for the ACE model. Statistical power to detect additive genetic variation under the ACE model was derived analytically for least-squares, goodness-of-fit and maximum likelihood-based test statistics. The noncentrality parameter for the likelihood ratio test statistic is shown to be a simple function of the MZ and DZ intraclass correlation coefficients and the proportion of MZ and DZ twin pairs in the sample. All theoretical results were validated using simulation. The derived expressions can be used to calculate power of the classical twin design in a simple and rapid manner.

Currently, mapping genes for complex human traits relies on two complementary approaches, linkage and association analyses. Both suffer from several methodological and theoretical limitations, which can considerably increase the type-1 error rate and reduce the power to map human quantitative trait loci (QTL). This review focuses on linkage methods for QTL mapping. It summarizes the most common linkage statistics used, namely Haseman–Elston-based methods, variance components, and statistics that condition on trait values. Methods developed more recently that accommodate the X-chromosome, parental imprinting and allelic association in linkage analysis are also summarized. The type-I error rate and power of these methods are discussed. Finally, rough guidelines are provided to help guide the choice of linkage statistics.

People are intensely interested in factors underlying earning power and what can be done to enhance it. A recent study using monozygotic male twins adds to knowledge in this area. Based on data from 136 twin pairs, the investigators favored a correlational hypothesis, namely that simply being married raises salaries by 19 to 26%. Following a review of this research, summaries of twin studies presented at the biennial meeting of the International Society for Human Ethology in Ghent, Belgium (July 27–30, 2004) and at the annual meeting of the Human Behavior and Evolution Society in Berlin, Germany (July 21–25, 2004) are presented. The final section of this article provides information of general interest to twin researchers, physicians and others working in twin-related fields.