This article discusses new latent variable techniques developed by the authors. As an illustration, a new factor mixture model is applied to the monozygotic–dizygotic twin analysis of binary items measuring alcohol-use disorder. In this model, heritability is simultaneously studied with respect to latent class membership and within-class severity dimensions. Different latent classes of individuals are allowed to have different heritability for the severity dimensions. The factor mixture approach appears to have great potential for the genetic analyses of heterogeneous populations. Generalizations for longitudinal data are also outlined.

A transmission disequilibrium test for quantitative traits which combines association and linkage analyses is currently available in several dedicated software packages. We describe how to implement such models in linear mixed model procedures that are available in widely used statistical packages such as SPSS. We also briefly mention a few extensions of the model that become naturally available once the model is implemented in such procedures.

Maximum likelihood estimation techniques are widely used in twin and family studies, but soon reach computational boundaries when applied to highly complex models (e.g., models including gene-by-environment interaction and gene–environment correlation, item response theory measurement models, repeated measures, longitudinal structures, extended pedigrees). Markov Chain Monte Carlo (MCMC) algorithms are very well suited to fit complex models with hierarchically structured data. This article introduces the key concepts of Bayesian inference and MCMC parameter estimation and provides a number of scripts describing relatively simple models to be estimated by the freely obtainable BUGS software. In addition, inference using BUGS is illustrated using a data set on follicle-stimulating hormone and luteinizing hormone levels with repeated measures. The examples provided can serve as stepping stones for more complicated models, tailored to the specific needs of the individual researcher.

In a recent article McArdle and Prescott (2005) showed how simultaneous estimation of the bio-metric parameters can be easily programmed using current mixed-effects modeling programs (e.g., SAS PROC MIXED). This article extends these concepts to deal with mixed-effect modeling of longitudinal twin data. The biometric basis of a polynomial growth curve model was used by Vandenberg and Falkner (1965) and this general class of longitudinal models was represented in structural equation form as a latent curve model by McArdle (1986). The new mixed-effects modeling approach presented here makes it easy to analyze longitudinal growth-decline models with biometric components based on standard maximum likelihood estimation and standard indices of goodness-of-fit (i.e., χ2, df, εa). The validity of this approach is first checked by the creation of simulated longitudinal twin data followed by numerical analysis using different computer programs (i.e., Mplus, Mx, MIXED, NLMIXED). The practical utility of this approach is examined through the application of these techniques to real longitudinal data from the Swedish Adoption/Twin Study of Aging (Pedersen et al., 2002). This approach generally allows researchers to explore the genetic and nongenetic basis of the latent status and latent changes in longitudinal scores in the absence of measurement error. These results show the mixed-effects approach easily accounts for complex patterns of incomplete longitudinal or twin pair data. The results also show this approach easily allows a variety of complex latent basis curves, such as the use of age-at-testing instead of wave-of-testing. Natural extensions of this mixed-effects longitudinal approach include more intensive studies of the available data, the analysis of categorical longitudinal data, and mixtures of latent growth-survival/ frailty models.

Nonnormal phenotypic distributions introduce significant problems in the estimation and selection of genetic models. Here, a semiparametric maximum likelihood approach to analyzing non-normal phenotypes is described. In this approach, distributions are explicitly modeled together with genetic and environmental effects. Distributional parameters are introduced through mixture constraints, where the distribution of effects are discretized and freely estimated rather than assumed to be normal. Semiparametric maximum likelihood estimation can be used with a variety of genetic models, can be extended to a variety of pedigree structures, and has various advantages over other approaches to modeling nonnormal data.

Twin registries form an exceptionally rich source of information that is largely unexploited for phenotypic analyses. One obstacle to straightforward phenotypic statistical analysis is the inherent dependency, which is due to the clustering of cases within families. The present simulation study gauges the degree of the bias produced by the dependency of family data on the estimates of standard errors and chi-squared, when they are treated as independent observations in a phenotypic model, and assesses the efficiency of an estimator, which corrects for dependency. When family-clustered data are used for phenotypic analysis, in treating individuals as independent, and using standard maximum likelihood estimation, there is a tendency for the chi-square statistic to be overestimated, and the standard errors of the parameters to be underestimated. The bias increases with family resemblance, due to heritability or shared environment. The source of family resemblance — either heritability (h2) and/or shared environment (c2) — interacts with the composition of the sample. In the absence of c2, samples with twins, parents and spouses show the lowest bias, whereas in the presence of c2 samples with only twins show the lowest bias. In all conditions the bias remained below 15%. The use of the ‘complex option’ available in Mplus (clustering corrected robust maximum likelihood estimation) reduces the bias to the levels observed when only independent cases are considered. Thus with the use of robust estimates the bias due to family dependency becomes practically negligible in all conditions of dependency. In conclusion, the present study shows that the bias due to dependency in family data does not form a serious obstacle to phenotypic data analysis.

This article is concerned with the power to detect the presence of genotype by environment interaction (G × E) in the case that both genes and environment feature as latent (i.e., unmeasured) variables. The power of the test proposed by Jinks and Fulker (1970), which is based on regressing the absolute difference between the scores of monozygotic twins on the sums of these scores, is compared to the power of an alternative test, which is based on Marginal Maximum Likelihood (MML). Simulation studies showed that generally the power of the MML-based test was greater than the power of the Jinks and Fulker test in detecting linear and curvilinear G × E interaction, regardless of whether the distribution of the data deviated significantly from normality. However, after a normalizing transformation, the Jinks and Fulker test performed slightly better. Some possible future extensions of the MML-based test are briefly discussed.

The objective of this study was to evaluate the impact of variations of the angiotensinogen (AGT) and angiotensin II type I receptor (AGTR1) genes on progression of blood pressure (BP) and left ventricular mass (LVM) in multiethnic youth. The study was longitudinal involving 581 European American (EA) and African American (AA) youth with 12 assessments over a 15-year period. AGT M235T and three AGTR1 polymorphisms (C-521T, L191L and A1166C) were genotyped and individual growth curve modeling analyses were conducted. Single nucleotide polymorphism (SNP) analyses found a significant 3-way interaction between M235T, ethnicity and gender on BP levels. Systolic BP (SBP) levels were 5.8 mmHg (p = .00003) and diastolic BP (DBP) levels were 2.6 mmHg (p = .005) lower in carriers versus noncarriers of the M235 allele in AA males only. Furthermore, the AGTR1 L191 allele showed a SBP lowering effect in subjects with a high socioeconomic status (SES; p = .048) and a DBP lowering effect in AAs (p = .038). Haplotype analyses identified a protective haplotype (C-521, 191L and A1166) for LVM levels (p = .03). LVM in individuals homozygous for this haplotype was 12.9 g lower than those homozygous for the most common haplotype (–521T, 191L and A1166). No significant interactions were found between the AGT M235T polymorphism and any of the single SNPs or haplotypes of the AGTR1 gene. Our results in multiethnic youth uncover an ethnicity and gender-specific effect of the AGT M235T polymorphism and a SES or ethnicity-specific effect of the AGTR1 L191L polymorphism on the progression of hypertension risk. A protective AGTR1 haplotype for LVM was also identified.

In the classic twin design, estimation of genetic and environmental effects is based on the assumption that environmental influences are shared to the same extent by monozygotic and dizygotic twins (equal environment assumption, EEA). We explore the conditions in which the EEA can be tested based on multivariate phenotypic data. We focus on the test whether the correlation between shared environmental factors in dizygotic twins (rC) is less than 1. First, model identification was investigated analytically in Maple and Mx. Second, statistical power was examined in Mx. Third, the amount of bias caused by violation of the EEA was evaluated. Finally, applications to empirical data concern spatial ability in adolescents and aggression in children. Bivariate and trivariate models include several instances in which the EEA can be tested. The number of twin pairs that is needed to detect violation of the EEA with a statistical power of .80 (α = .05) varied between 508 and 3576 pairs for the situations considered. The bias in parameter estimates, given misspecification, ranged from 5% to 34% for additive genetic effects, and from 4% to 34% for shared environmental effects. Estimates of the nonshared environmental effects were not biased. The EEA was not violated for spatial ability or aggression. Multivariate data provide sufficient information to test the validity of the EEA. The number of twin pairs that is needed is no greater than the number typically available in most twin registries. The analysis of spatial ability and aggression indicated no detectable violation of the EEA.

Approaches such as DeFries-Fulker extremes regression (LaBuda et al., 1986) are commonly used in genetically informative studies to assess whether familial resemblance varies as a function of the scores of pairs of twins. While useful for detecting such effects, formal modeling of differences in variance components as a function of pairs' trait scores is rarely attempted. We therefore present a finite mixture model which specifies that the population consists of latent groups which may differ in (i) their means, and (ii) the relative impact of genetic and environmental factors on within-group variation and covariation. This model may be considered as a special case of a factor mixture model, which combines the features of a latent class model with those of a latent trait model. Various models for the class membership of twin pairs may be employed, including additive genetic, common environment, specific environment or major locus (QTL) factors. Simulation results based on variance components derived from Turkheimer and colleagues (2003), illustrate the impact of factors such as the difference in group means and variance components on the feasibility of correctly estimating the parameters of the mixture model. Model-fitting analyses estimated group heritability as .49, which is significantly greater than heritability for the rest of the population in early childhood. These results suggest that factor mixture modeling is sufficiently robust for detecting heterogeneous populations even when group mean differences are modest.

In order to determine if twinning impacted achievement of motor milestones the attainment of early motor milestones in twins was examined and compared to published data from singletons of the same age from the same culture and birth years. We examined the influence of twinning, sex, zygosity and birth cohort (1987–2001) on the motor development of twins aged 0 to 24 months. Data on the attainment of motor milestones (turn, sit, crawl, stand and walk) of twins were collected from maternal reports. All data were corrected for gestational age. Data from the twin sample were compared to normative data from singletons, which were available from Child Health Clinics (CHC). Analyses across twin data and the CHC singleton data revealed no differences between twins and singletons in achievement of motor milestones. Girls were able to sit without support slightly earlier than boys, otherwise there were no other sex differences. Birth-order analyses revealed minimal but significant differences in turning over from back to belly and for sitting without support between the first- and second-born. Dizygotic (DZ) twins were faster than monozygotic (MZ) twins in achieving the moment of sit, crawl, stand and walk. Twins born in earlier cohorts were faster in reaching the moment of crawl, sit and walk. It is concluded that there are no differences in time of reaching motor milestones between twins and singletons within the normal range. Sex has minimal to no effect on motor development in early childhood. DZ twins achieve motor milestones sooner than MZ twins. Attainment of gross motor milestones (crawl, stand and walk) is delayed in later birth cohorts.

In the population-based FinnTwin16 study, proportions of genetic and environmental factors contributing to muscle dissatisfaction and muscle-enhancing substance use were assessed in 319 pairs of twin brothers: 141 monozygotic (MZ) and 178 dizygotic (DZ) pairs. In addition there were 86 twin individuals from pairs in which only one co-twin responded. Of all respondents, 30% experienced high muscle dissatisfaction. The corresponding proportion of muscle-enhancing substance use was 10%. The subjects were similar in age (23.8 years, 95% confidence interval [CI] 23.76–23.84), body mass index (23.7, 95% CI 23.5–23.9), and waist circumference (84.5 cm, 95% CI 83.7–85.2), independent of their muscle dissatisfaction or muscle-enhancing substance use status and independent of their zygosity. The MZ polychoric correlation for muscle dissatisfaction was .39 (95% CI .17–.58) and .27 for DZ pairs (95% CI .07–.46). The MZ tetrachoric correlation for muscle-enhancing substance use was .65 (95% CI .28–.87) and .56 for DZ pairs (95% CI .26–.78). The AE model, where additive genetic factors (A) accounted for 42% (95% CI .23–.59) and unique environmental factors (E) 58% (95% CI .41–.77) of the liability, provided the best fit for muscle dissatisfaction. The CE model, where common environmental factors (C) accounted for 60% (95% CI .37–.77) and unique environmental factors (E) 40% (95% CI .23–.63) of the liability, provided the best fit for muscle-enhancing substance use. Both genetic and unique (nonfamilial) environmental factors are involved in muscle dissatisfaction in the population. Nongenetic factors (both familial and non-familial) appear to best explain the use of muscle-enhancing substances.

The aim of this tertiary hospital–based cohort study was to determine and compare perinatal outcome and neonatal morbidities of pregnancies with twin–twin transfusion syndrome (TTTS) before and after the introduction of a treatment program with laser ablation of placental communicating vessels. Twenty-seven pregnancies with Stage II–IV TTTS treated with amnioreduction were identified (amnioreduction group). The data were compared with that obtained from the first 31 pregnancies with Stage II–IV TTTS managed with laser ablation of placental communicating vessels (laser group). Comparisons were made for perinatal survival and neonatal morbidities including abnormalities on brain imaging. The median gestation at therapy was similar between the two groups (20 vs. 21 weeks, p = .24), while the median gestation at delivery was significantly greater in the laser treated group (34 vs. 28 weeks, p = .002). The perinatal survival rate was higher in the laser group (77.4% vs. 59.3%, p = .03). Neonatal morbidities including acute respiratory distress, chronic lung disease, requirement for ventilatory assistance, patent ductus arteriosus, hypotension, and oliguric renal failure had a lower incidence in the laser group. On brain imaging, ischemic brain injury was seen in 12% of the amnioreduction group and none of the laser group of infants (p = .01). In conclusion, these findings indicate that perinatal outcomes are improved with less neonatal morbidity for monochorionic pregnancies with severe TTTS treated by laser ablation of communicating placental vessels when compared to treatment by amnioreduction.

The rapid increase in twinning rates in developed countries has increased interest in the question as to whether twin mothers have higher mortality and more health problems than mothers of singletons. Here we use a national survey, the Office for National Statistics Longitudinal Study of England & Wales, and a linkage between the Danish Twin Registry and the Danish population register to examine mortality patterns after age 45 (50 for fathers) for twin parents and the whole population born from 1911 to 1950. For England and Wales, presence of limiting long-term illnesses and self-rated health status was also investigated. Overall similar health and mortality was found for twin parents and the whole population although both life table methods and survival analysis suggested a slight excess mortality among older cohorts of twin mothers in England and Wales.

Current early diagnosis, surveillance and intervention options make it hard to determine the natural course of twin pregnancies, especially regarding spontaneous preterm delivery and perinatal mortality. We studied the natural course in monochorionic (MC) and dichorionic (DC) twin pregnancies in a historical cohort. Twin pregnancies were studied in a unique database of 651 twin pairs born in the period 1907 to 1938. We examined the effect of chorionicity on gestational age, birthweight, peri-natal mortality, intertwin birthweight differences, the incidence of preeclampsia and maternal mortality. Perinatal mortality was 27.7% for MC and 15.8% for DC twins (p < .001). Gestational age and birthweight were stronger predictors of perinatal mortality than chorionicity. Perinatal outcome was poorer for the second twin, especially in DC twins. Delivery before 37 weeks of gestation occurred more often in MC twin pregnancies (48.8% compared to 33.3% in DC twin pregnancies). DC twins were on average 288 g (95% confidence interval 201–376) heavier than MC twins. Severe birthweight discordancy occurred equally in MC and DC twins (18.1%). However, if present, mortality was only increased in MC twins. The birthweight of girls was not affected by the presence of a male co-twin. In this historical cohort MC twin pregnancies had a higher perinatal mortality, caused by a high incidence of low birthweight mainly due to preterm delivery. Mortality did not differ in deliveries after 31 weeks of gestation, which is in contrast to recent data. Apparently, modern obstetrics is more effective in reducing mortality in DC twins.

There are only a few reports of fetal parvovirus infection in the circumstance of a twin pregnancy. We report a case of differential fetal infection following maternal parvovirus B19 infection in a dichorionic twin pregnancy culminating in a dual live-birth. A 32-year-old woman was diagnosed with parvovirus infection following exposure to her infected child at 19 weeks' gestation in a dichorionic twin gestation. Maternal IgG seroconversion was documented and maternal blood parvovirus B19 DNA was detected by PCR testing. Fetal monitoring with serial ultrasound assessment was instituted. At 25 weeks' gestation Twin I (male) displayed minor ascites, small pericardial effusion, placentomegaly and oligohydramnios. Middle cerebral artery peak systolic velocity (MCA PSV) studies were abnormal. Twin II (female) was sonographically unremarkable. A single fetal intravascular transfusion for Twin I was performed (pretransfusion Hb 80 g/L). Twin I fetal blood parvovirus B19 DNA was detected by polymerase chain reaction (PCR) and serum demonstrated both B19 IgG and IgM. Following fetal transfusion the hydrops resolved, although the placentomegaly persisted. Two live infants were delivered at 37 weeks' gestation. Individual neonatal venepuncture detected B19 DNA by PCR in Twin I but not in Twin II. B19 IgM was present in Twin I but not Twin II. Both neonates had B19 IgG antibodies. Placental histopathology demonstrated mild edema for Twin I but no inclusion cells. The placenta of Twin II was unremarkable. This case demonstrates the ability for differential transplacental infection of this virus and the assistance of fetal MCA flow studies to guide therapy in a multiple pregnancy at risk of parvovirus infection.

Population-based studies in twins have been of insufficient size to explore the relationship between risk of cerebral palsy and intrauterine growth. Earlier studies in singletons have suggested an optimum size at birth for minimum cerebral palsy risk between the 75th and 90th percentiles of weight for gestational age. We aggregated data from nine European cerebral palsy registers for 1976 to 1990. Using sex-specific fetal growth standards for twins, a z score of weight-for-gestation was derived for each of the 373 twin cases. The rates of cerebral palsy in each z-score band were compared to the rate in the a priori reference band of 0.67 to less than 1.28 (equivalent to the 75th to less than 90th percentiles). In twins born at 32 weeks' gestation or more (92% of all twins), cerebral palsy rates were higher for both light and heavy-forgestation babies compared to an optimum (i.e., minimum risk) in the reference band. However, the rate ratio for heavy babies (90th percentile or greater) did not reach conventional (95% confidence intervals [CI]) statistical significance (rate ratios = 1.76; 90% CI 1.02–3.03). For twins born at less than 32 weeks, the significantly higher risk for cerebral palsy was observed consistently in all z-score bands less than average compared to the reference band. This multi-center study demonstrates that for twins born at 32 weeks' gestation or more, an increased risk of cerebral palsy is associated with deviations from optimal intrauterine growth at about 1 standard deviation above mean weight, as was earlier reported for singletons. For twins born at less than 32 weeks' gestation, this pattern is only demonstrable for babies weighing below the optimum weight-for-gestation.

Do women experience orgasm because this trait was shaped by natural selection to augment female fitness? Or are women merely the lucky recipients of developmental patterns favored by selection to produce orgasm in males? A recent and widely publicized book by Elisabeth Lloyd (2005a) contends that there is insufficient evidence to validate any of the adaptive explanations yet proposed for female orgasm. We agree. But our reading of the data differs from Lloyd's. In this essay, we outline why, unlike Caton (2006), whose review of Lloyd's book appeared previously in this journal, we are not persuaded by Lloyd's argument that female orgasm is a nonadaptive byproduct of orgasm in men. We hold this view because we disagree with the criteria Lloyd uses to evaluate evolutionary hypotheses, and because we believe Lloyd defines female orgasm too narrowly, ignoring critical information about its affective aspects.

New legislation giving parents a voice in deciding their twins' school placement situation (same or separate classrooms) was passed in Minnesota in spring 2005. Since then, parents in several other states have started petitions and lobbying efforts to persuade their senators and representatives to follow suit. A review and update of these exciting developments is presented, followed by a report from the recently established Asian Society for Twin Studies. Reviews of two new twin studies — bases of political attitudes and age effects on dizygotic twinning — are presented. The uniquely informative lives of several twin pairs are also documented.