Few papers have attempted to address the potential of extended kinships of twins to resolve the complexities of biological and cultural inheritance in humans. Since the mid-80s these issues have largely been buried beneath the quest for specific genes that contribute to individual differences in complex traits and liability to disease. The articles of Keller et al. and Medland and Keller (current issue) revisit these issues. History will decide whether these new papers represent the final gasp of a paradigm superceded by the ‘new’ genetics or contain the timely seeds of new birth in the face of a 30-year genetic research program otherwise poised on the cusp of degeneration (Lakatos & Musgrave, 1970).

The classical twin design uses data on the variation of and covariation between monozygotic and dizygotic twins to infer underlying genetic and environmental causes of phenotypic variation in the population. By using data from additional relative classes, such as parents, extended twin family designs more comprehensively describe the causes of phenotypic variation. This article introduces an extension of previous extended twin family models, the Cascade model, which uses information on twins as well as their siblings, spouses, parents, and children to differentiate two genetic and six environmental sources of phenotypic variation. The Cascade also relaxes assumptions regarding mating and cultural transmission that existed in previous extended twin family designs. The estimation of additional parameters and relaxation of assumptions is potentially important, not only because it allows more fine-grained descriptions of the causes of phenotypic variation, but more importantly, because it can reduce the biases in parameter estimates that exist in earlier designs.

Modeling the data from extended twin pedigrees allows the estimation of increasing complex covariance relationships in which the effects of cultural transmission, nonrandom mating and genotype x environment covariation can be incorporated. However, the power to detect these effects in existing data sets has not yet been examined. The present study examined the effects that different family structures (i.e., the ratio of MZ to DZ families and the importance of cousins vs. avuncular relatives) have on statistical power. In addition, we examined the power to detect genetic and environmental effects within the context of two large data sets (VA30K and the OZVA60K). We found that power to detect additive genetic and cultural transmission effects were maximized by over sampling MZ families. In terms of ascertainment, there was little difference in power between samples that had focused on recruiting a third generation (the children of twins) versus those that had focused on recruiting the siblings of the twins. In addition, we examined the power to detect additive and dominant genetic effects, cultural transmission and assortative mating in the existing VA30K and OZVA60K samples, under two different models of mating: phenotypic assortment and social homogamy. There was nearly 100% power to detect assortative mating and cultural transmission, against a background of small additive and dominant genetic and familial environmental effects. In addition, the power to detect additive or dominant genetic effects quickly asymptoted, so that there was almost 100% power to detect effects explaining 20% or more of the total variance. These results demonstrate that the Cascade model has sufficient power to detect parameters of interest in existing datasets. Mx scripts are available from www.vipbg.vcu.edu/~sarahme/cascade.

The extended twin kinship design allows the simultaneous testing of additive and nonadditive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission (Eaves et al., 1999). It also handles the contribution of these sources of variance to the (co)variation of multiple phenotypes. Keller et al. (2008) extended this comprehensive model for family resemblance to allow or a flexible specification of assortment and vertical transmission. As such, it provides a general framework which can easily be reduced to fit subsets of data such as twin-parent data, children-of-twins data, etc. A flexible Mx specification of this model that allows handling of these various designs is presented in detail and applied to data from the Virginia 30,000. Data on height, body mass index, smoking status, church attendance, and political affiliation were obtained from twins and their families. Results indicate that biases in the estimation of variance components depend both on the types of relative available for analysis, and on the underlying genetic and environmental architecture of the phenotype of interest.

Linkage disequilibrium (LD), the association in populations between genes at linked loci, has achieved a high degree of prominence in recent years, primarily because of its use in identifying and cloning genes of medical importance. The field has recently been reviewed by Slatkin (2008). The present article is largely devoted to a review of the theory of LD in populations, including historical aspects.

Epidemiological studies report a high prevalence of type 2 diabetes and metabolic syndrome in the island nation of Mauritius. The Mauritius Family Study was initiated to examine heritable factors that contribute to these high rates of prevalence and consists of 400 individuals in 24 large extended multigenerational pedigrees. Anthropometric and biochemical measurements relating to the metabolic syndrome were undertaken in addition to family and lifestyle based information for each individual. Variance components methods were used to determine the heritability of the type 2 diabetes and metabolic syndrome related quantitative traits. The cohort was made up of 218 females (55%) and 182 males with 22% diagnosed with type 2 diabetes and a further 30% having impaired glucose tolerance or impaired fasting glucose. Notably BMI was not significantly increased in those with type 2 diabetes (P = .12), however a significant increase in waist circumference was observed in these groups (P = .02). The heritable proportion of trait variance was substantial and greater than values previously published for hip circumference, LDL and total cholesterol, diastolic and systolic blood pressure and serum creatinine. Height, weight and BMI heritabilities were all in the upper range of those previously reported. The phenotypic characteristics of the Mauritius family cohort are similar to those previously reported in the Mauritian population with a high observed prevalence rate of type 2 diabetes. A high heritability for key type 2 diabetes and metabolic syndrome related phenotypes (range 0.23 to 0.68), suggest the cohort will have utility in identifying genes that influence these quantitative traits.

Objective: A recent Children-of-Female-Twin design suggests that the association between maternal alcohol use disorder and offspring ADHD is due to a combination of genetic and environmental factors, such as prenatal nicotine exposure. We present here a complementary analysis using a Children-of-Male-Twin design examining the association between paternal alcoholism and offspring attention deficit hyperactivity problems (ADHP). Methods: Children-of-twins design: offspring were classified into 4 groups of varying genetic and environmental risk based on father and co-twin's alcohol dependence status. Results: Univariate results are suggestive of a genetic association between paternal alcohol dependence and broadly defined offspring ADHP. Specifically, offspring of male twins with a history of DSM-III-R alcohol dependence, as well as offspring of non-alcohol dependent monozygotic twins whose co-twin was alcohol dependent, were significantly more likely to exhibit ADHP than control offspring. However, multivariate models show maternal variables independently predicting increased risk for offspring ADHP and significantly decreased support for a genetic mechanism of parent-to-child transmission. Conclusions: In support of earlier work, maternal variables (i.e., maternal ADHD and prenatal exposure) were strongly associated with child ADHP; however, the role of paternal alcohol dependence influences was not definitive. While genetic transmission may be important, the association between paternal alcohol dependence and child ADHP is more likely to be indirect and a result of several pathways.

Two major challenges to conducting a community-based twin study of pathological gambling (PG) disorder are that: (a) it is relatively rare, and (b) individuals with the disorder in the community may be difficult to locate and recruit. We describe a new study of 4,764 individuals recruited from the Australian Twin Registry in which we attempt to effectively deal with the first challenge and examine the impact of the second challenge. The lifetime prevalence of DSM-IV PG in this Australian twin sample was 2.2%, which is 400–500% higher than has been obtained in prevalence surveys conducted in the United States. A number of predictors of non-participation were identified, including a lifetime PG disorder diagnosis, but these did not have a large net effect on the estimated number of individuals with PG or related characteristics in the twin sample. Results of biometric modeling suggested that the effect of genetic, shared family environmental, and nonshared environmental influences on the propensity to engage in 11 different specific forms of gambling (e.g., playing the lottery, betting on horse or dog races, playing electronic gaming machines) were generally moderate, low, and moderate, respectively, with mean parameter estimates obtained of 43%, 10%, and 46%. An intriguing comparison with results from a 1963 US adolescent twin study conducted by Loehlin and Nichols (1976) suggests that: (a) propensity genes for gambling involvement may be more likely to be expressed in the heavy-gambling Australian culture, or that (b) the family environment has a transient effect on the gambling behavior of young people.

This study presents a general model of two binary variables and applies it to twin sex pairing data from 21 twin data sources to estimate the frequency of dizygotic twins. The purpose of this study is to clarify the relationship between maximum likelihood and Weinberg's differential rule zygosity estimation methods. We explore the accuracy of these zygosity estimation measures in relation to twin ascertainment methods and the probability of a male. Twin sex pairing data from 21 twin data sources representing 15 countries was collected for use in this study. Maximum likelihood estimation of the probability of dizygotic twins is applied to describe the variation in the frequency of dizygotic twin births. The differences between maximum likelihood and Weinberg's differential rule zygosity estimation methods are presented as a function of twin data ascertainment method and the probability of a male. Maximum likelihood estimation of the probability of dizygotic twins ranges from 0.083 (95% approximate CI: 0.082, 0.085) to 0.750 (95% approximate CI: 0.749, 0.752) for voluntary ascertainment data sources and from 0.374 (95% approximate CI: 0.373, 0.375) to 0.987 (95% approximate CI: 0.959, 1.016) for active ascertainment data sources. In 17 of the 21 twin data sources differences of 0.01 or less occur between maximum likelihood and Weinberg zygosity estimation methods. The Weinberg and maximum likelihood estimates are negligibly different in most applications. Using the above general maximum likelihood estimate, the probability of a dizygotic twin is subject to substantial variation that is largely a function of twin data ascertainment method.

Studies have reported that refractive errors are associated with premature births. As twins have higher prevalence of prematurity than singletons, it is important to assess similarity of the prevalence of refractive errors in twins and singletons for proper interpretations and generalizations of the findings from twin studies. We compared refractive errors and diopter hours between 561 pairs of twins and 3757 singletons who are representative of school-age children (7–15 years) residing in an urban area of southern China. We found that the means and variances of the continuous measurement of spherical equivalent refractive error and diopter hours were not significantly different between twins and singletons. Although the prevalence of myopia was comparable between twins and singletons, that of hyperopia and astigmatism was slightly but significantly higher in twins than in singletons. These results are inconsistent with those of adult studies that showed no differences in refractive errors between twins and singletons. Given that the sample size of twins is relatively small and that this study is the first to demonstrate minor differences in refractive errors between twins and singletons, future replications are necessary to determine whether the slightly higher prevalence of refractive errors in twins than in singletons found in this study was due to a sampling error or to the developmental delay often observed in twins in childhood.

This study examines the probability of twins by birth year, maternal race–ethnicity, age, and parity and the influences of these demographic factors on the probability of male in twins and singletons in a large, racially diverse population. Recent publications note steep increases in twin births while the probability of male births has been reported to vary by parental race–ethnicity and age and birth order. Probability of male stratified by plurality has not been investigated in California prior to this study. Cubic spline estimates and Poisson regression techniques were employed to describe trends in twins and males using California vital statistics birth and fetal death records over the period from 1983–2003. This study includes 127,787 twin pair and 11,025,106 singleton births. The probability of twins varied by birth year, maternal race–ethnicity, age, and parity. The probability of twins increased by 10.1% from 1983–1992 and increased by 20.1% from 1993–2003, nearly doubling the previous increase. All maternal race–ethnicity groups showed increases in probability of twins with increasing maternal age. Parous women compared to nulliparous women had larger increases in the probability of twins. The probability of males in twins decreased from 1983–1992 and increased from 1993–2003; while in singletons the probability appeared unchanged. These findings show increases in the probability of twins in California from 1983–2003 and identify maternal age, race–ethnicity, and parity groups most likely to conceive twins. The cause of the increase in twins is unknown but coincides with trends towards delayed childbearing and increased use of subfertility treatments.

The propensity to take risk underpins a wide variety of decision-making behavior, ranging from common ones such as asking for directions and trying out a new restaurant to more substantial economic decisions involving, for instance, one's investment or career. Despite the fundamental role of risk attitude in the economy, its genetic basis remains unknown. Using an experimental economics protocol combined with a classical twin strategy, we provide the first direct evidence of the heritability of economic risk attitude, at 57%. We do not find a significant role for shared environmental effects, a common observation in behavioral genetics that is contrary to commonly held views in economics. Our findings complement recent neuroeconomic studies in enhancing the understanding of the neurobiological basis of risk taking.

The physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic syndrome components and related diseases and risk factor levels, status of arteries, structure and function of the heart, bone properties, and muscle and fat tissue-related mechanisms linked to physical activity and chronic disease development. Our physical activity assessments showed that inactive co-twins were on average 8.8 MET hours/day less active than their active co-twins through out their midlife (2.2 ± 2.3 vs. 11.0 ± 4.1 MET h/day, p < .001). Follow-up fitness tests showed that physically inactive co-twins were less fit than their active co-twins (estimated VO2peak 26.4 ± 4.9 vs. 32.5 ± 5.5 ml/kg/min, p < .001). Similar differences were found in both MZ and DZ pairs. On the basis of earlier epidemiological observations on nonrelated individuals, these physical activity and fitness differences are large enough to cause differences in many mechanisms and risk factors related to the development of chronic diseases and to permit future analyses.

Using the South Korean national live birth data for the years 2003 to 2007, monozygotic (MZ) and dizygotic (DZ) twin birth rates were estimated and analyzed by maternal age, and parents of twins and those of singletons were compared in their level of education. During this period, while the MZ twin birth rate showed no change, the DZ twin birth rate increased up to 9.4 pairs per thousand births. This rate is close to five times as high as the natural DZ twinning rate in the South Korean population. The highest twinning rate occurred among mothers aged 30 to 34 years, followed by mothers aged 25 to 29. These results represented the first evidence for the downward trend in ages of mothers of twins. In each year between 2003 and 2006, percentages of parents who completed college or higher level of education were higher in the twin than in the singleton group, suggesting that the parental socioeconomic level became higher in twins than in singletons. We speculated that these demographic changes occurred because assisted reproductive technology was more easily available among parents of high socioeconomic status. In their sampling strategies, twin researchers should consider our findings of recent changes in demographic characteristics of parents of twins as well as increased DZ twin birth rates.

A forgotten story of monozygotic twins reared apart is described. The pair, born in 1941 in Fribourg, Switzerland, were separated due to switch-baby incident in the hospital. This caused one twin to be raised as a singleton by an unrelated family, and the other twin to be raised as a ‘dizygotic’ twin with an unrelated child. This is followed by reviews of recent twin research and case studies of X-inactivation and hemophilia, breast reconstruction, chimerism and life histories. The final section of the article includes human interest pieces on academic twins, dating twins, transsexual twins and athletic twins.