Cystic fibrosis (CF), the most common severe autosomal recessive trait among Caucasians, is caused by molecular lesions in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The course of the multi-organ disease CF is highly variable, suggesting the influence of environmental factors and/or modulating genes other than CFTR on the disease phenotype. To evaluate the cause of CF disease variability, the European CF Twin and Sibling Study collected data on two clinical parameters most sensitive for the course and prognosis of CF, ie weight predicted for height (wfh)% (representative for the nutritional status) and FEVPerc (representative for the pulmonary status) for a cohort of 277 sibling pairs, 12 pairs of dizygous twins and 29 pairs of monozygous twins. Of these 318 CF twin and sib pairs, 114 were reported to be homozygous for the most frequent CF disease-causing lesion, ΔF508. Intra-pair discordance was assessed by the intra-pair differences with wfh% and FEVPerc and by DELTA, a composite parameter defined by linear combination of wfh% and FEVPerc in order to describe discordance with respect to the overall disease severity. Monozygous twins had a significantly lower DELTA than dizygous twins (P = 0.05) indicating that CF disease severity is modulated by an inherited component in addition to the CFTR gene itself. Extreme phenotypes are considered to be more informative for the analysis of any quantitative trait. Thus, we aimed to quantify disease severity and intra-pair discordance in order to select pairs with the extreme phenotypes DIS (discordant patient pairs), CON+ (concordant and mildy affected patient pairs) and CON− (concordant and severely affected patient pairs). The algorithm reliably discriminated between pairs DIS, CON+ and CON− among the cohort of ΔF508 homozygotes. The selected pairs from these categories demonstrated non-overlapping properties for wfh%, FEVPerc and the intra-pair difference of both parameters. Twin Research (2000) 3, 277–293.

The aim of this study was to estimate the rates of recovery, treatment-seeking, and natural recovery from pathological gambling (PG) in men and women in a community-based national survey, and to examine the role of gambling problem recognition in recovery from PG. Participants were 4,764 individuals from a community-based Australian national twin registry (104 with a lifetime history of PG) who were administered a structured psychiatric telephone interview. Women were more likely than men to recover from (56% versus 36%; odds ratio = 2.3) and to seek treatment for PG (32% versus 13%; odds ratio = 3.2). Most individuals who recovered from PG did so without treatment (82%), but this was higher among men than among women (92% versus 57%; odds ratio = 5.3). This is the first study to document sex differences in treatment-seeking and recovery from PG. These findings highlight the value in continuing to develop self-help and brief treatments for PG that will appeal to those who are unlikely to seek formal help.

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

The primary aim of the Michigan State University Twin Registry (MSUTR) is to examine developmental differences in genetic, environmental, and neurobiological influences on internalizing and externalizing symptoms, with disordered eating and antisocial behavior representing particular areas of interest. Twin participants span several developmental stages (i.e., childhood, adolescence, and young adulthood). Assessments include comprehensive, multiinformant measures of psychiatric and behavioral phenotypes, buccal swab and salivary DNA samples, assays of adolescent and adult steroid hormone levels (e.g., estradiol, progesterone, testosterone, cortisol), and videotaped parent–child interactions of child and adolescent twin families. To date, we have collected data on over 1000 twins, with additional data collections underway. This article provides an overview of the newly developed MSUTR and describes current and future research directions.

In a longitudinal study of Dutch adolescent and young adult twins, their parents and their siblings, questionnaire data were collected on depression, anxiety and correlated personality traits, such as neuroticism. Data were collected by mailed surveys in 1991, 1993, 1995 and 1997. A total of 13 717 individuals from 3344 families were included in the study. To localise quantitative trait loci (QTLs) involved in anxiety and depression, the survey data were used to select the most informative families for a genome-wide search. For each individual a genetic factor score was computed, based on a genetic multivariate analysis of anxiety, depression, neuroticism and somatic anxiety. A family was selected if at least two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low) and concordant (high-high and low-low) pairs were included in the selected sample. Once an extreme sibling pair was selected, all family members (parents and additional siblings of the selected pair) who had at least once returned a questionnaire booklet were asked to provide a DNA sample. In total, 2724 individuals from 563 families (1007 parents and 1717 offspring) were approached and 1975 individuals from 479 families (643 patients and 1332 offspring) complied by returning a buccal swab for DNA isolation. All offspring from selected families were asked to participate in a psychiatric interview and in a 24-hour ambulatory assessment of cardiovascular parameters and cortisol. The interview consisted of the WHO-Composite International Diagnostic Interview and was administered to 1253 offspring. In this paper we describe the genetic–epidemiological analyses of the survey data on anxiety, somatic anxiety, neuroticism and depression. We detail how these data were used to select families for the QTL study and discuss strategies that may help elucidate the molecular pathways leading from genes to anxious depression. Twin Research (2000) 3, 323–334.

The Danish Twin Registry is the oldest national twin register in the world, initiated in 1954, and, by the end of 2005, contained more than 75,000 twin pairs born in the between 1870 and 2004. The Danish Twin Registry is used as a source for studies on the genetic influence on normal variation in clinical parameters associated with the metabolic syndrome and cardiovascular diseases, clinical studies of specific diseases, and aging and age-related health problems. The combination of survey data, clinical data and linkage to national health-related registers enables follow-up studies of both the general twin population and twins from clinical studies. This paper summarizes the newest extension of the register and gives examples of new developments and phenotypes studied.

Monochorionic twins share a single placenta and are connected with each other through vascular anastomoses. Unbalanced inter-twin blood transfusion may lead to various complications, including twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). TAPS was first described less than a decade ago, and the pathogenesis of TAPS results from slow blood transfusion from donor to recipient through a few minuscule vascular anastomoses. This gradually leads to anemia in the donor and polycythemia in the recipient, in the absence of twin oligo-polyhydramnios sequence (TOPS). TAPS may occur spontaneously in 3–5% of monochorionic twins or after laser surgery for TTTS. The prevalence of post-laser TAPS varies from 2% to 16% of TTTS cases, depending on the rate of residual anastomoses. Pre-natal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and <1.0 in recipients). Post-natal diagnosis is based on large inter-twin hemoglobin (Hb) difference (>8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. Management includes expectant management, and intra-uterine blood transfusion (IUT) with or without partial exchange transfusion (PET) or fetoscopic laser surgery. Post-laser TAPS can be prevented by using the Solomon laser surgery technique. Short-term neonatal outcome ranges from isolated inter-twin Hb differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS. This review summarizes the current knowledge after 10 years of research on the pathogenesis, diagnosis, management, and outcome in TAPS.

All Norwegian twin pairs born 1967–1974 and still living in Norway in 1992 were invited to a health questionnaire study (Q1). 2,570 pairs (65%) participated. These cohorts and the twin cohorts born 1967–1979 were invited to a new questionnaire study (Q2) in 1998. This time 3,334 pairs (53%) participated. Almost all pairs having participated in the 1998 study were invited to an interview study of mental health (MHS), taking place 1999–2004. 1,391 complete pairs (44%) participated. The questionnaire studies included extensive data on somatic health with fewer items on mental health and demography. Health-related and demographic information available from the Medical Birth Registry on all invited twins was applied to predict participation to the first study. A few registry variables indicating poor health predicted nonparticipation in Q1. Health information and demography from Q1 were tested as predictors of participation in the follow-up study (Q2). Monozygosity, female sex, being unmarried, having no children, and high education predicted participation, whereas few indicators of poor mental and somatic health and unhealthy lifestyle moderately predicted nonparticipation in Q2. No health indicators reported in Q2 predicted further participation. Standard genetic twin analyses of indicators of various mental disorders from Q2, validated by diagnostic data from the MHS, did not indicate differences in genetic/environmental covariance structures between participants and nonparticipants in MHS. In general the results show a moderate selection towards good mental and somatic health. Attrition from Q2 to the MHS does not appear to affect twin analyses of mental health related variables.

Structural equation modeling (SEM) is an important research tool, both for path-based model specification (common in the social sciences) and also for matrix-based models (in heavy use in behavior genetics). We developed umx to give more immediate access, relatively concise syntax and helpful defaults for users in these two broad disciplines. umx supports development, modification and comparison of models, as well as both graphical and tabular outputs. The second major focus of umx, behavior genetic models, is supported via functions implementing standard multigroup twin models. These functions support raw and covariance data, including joint ordinal data, and give solutions for ACE models, including support for covariates, common- and independent-pathway models, and gene × environment interaction models. A tutorial site and question forum are also available.

The second to fourth finger length ratio (2d:4d) has been the subject of much recent work and is thought to be related to diverse gender and hormone-related traits including sports ability, disease susceptibility, attractiveness and sexuality. It is established in utero and remains constant in adulthood. Familial clustering has been thought to contribute to the development of 2d:4d from early studies but no twin studies exploring heritability have been reported to date. In this study, a sample of 456 female twin pairs (148 monozygotic [MZ], 308 dizygotic [DZ]) aged 18 to 79 years was used to estimate the heritability of 2d:4d for the right and left hands. Finger lengths were derived from hand xrays. Variance components analysis was used to estimate and contrast genetic and environmental effects on this phenotype. The mean 2d:4d was 0.92 (SD = 0.001) for both hands. The MZ intraclass correlation was higher than in DZ (.66 vs. .35 for right 2d:4d, and .71 vs. .37 for left 2d:4d). The best fit model included additive polygenic and unique environmental effects (‘AE’ model), with no significant common environmental effects detected. Heritability was estimated to be approximately 66% for 2d:4d (95% confidence interval 0.5–0.78). These results suggest a substantial genetic contribution to the determination of this hormonally related skeletal ratio in women, which could be more influential than the effects of common prenatal environmental factors. However the current study design does not preclude the possibility of confounding between heritability estimates and unobserved prenatal effects.

The Early Growth and Development Study is a prospective adoption study of birth parents, adoptive parents, and adopted children recruited in two cohorts (N = 561 triads). The primary study aims are to examine how family, peer, and contextual processes affect children's adjustment, and to examine their interplay (mediation, moderation) with genetic influences. Participants were recruited through adoption agencies located throughout the United States following the birth of a child. Assessments are ongoing, in 9-month intervals until the child reaches 3 years of age and in 1-year intervals thereafter through age 9. Data collection includes the following primary constructs: child temperament, social behavior, school performance, mental health, and health; birth and adoptive parent personality characteristics, mental health, competence, stress, health, context, substance use, parenting, and marital relations; and pregnancy use of drugs and maternal stress during pregnancy. DNA and salivary cortisol samples have also been collected. Analyses have indicated evidence for genotype-environment interactions during early childhood. Study procedures, sample representativeness (including tests of potential confounds in the adoption design), and an overview of findings to date are summarized, and future plans are described.

This study reports the first behavioral genetic investigation of the extent to which genetic and/or environmental factors contribute to the relationship between the Big Five personality factors and trait emotional intelligence. 213 pairs of adult monozygotic twins and 103 pairs of same-sex dizygotic twins completed the NEO-PI-R and the Trait Emotional Intelligence Questionnaire (TEIQue). Replicating previous non-twin studies, many significant phenotypic correlations were found between the Big Five factors — especially Neuroticism, Extraversion, and Conscientiousness — and the facets, factors, and global scores derived from the TEIQue. Bivariate behavioral genetic model-fitting analyses revealed that these phenotypic correlations were primarily attributable to correlated genetic factors and secondarily to correlated non-shared environmental factors. The results support the feasibility of incorporating EI as a trait within existing personality taxonomies.

The Colorado Twin Registry (CTR) is a population-based registry housed at the Institute for Behavioral Genetics, University of Colorado. Recruited subjects' birth years date from 1968. Four samples comprise the CTR: the Community Twin Sample, Infant Twin Sample, Longitudinal Twin Sample, and the Early Reading Development Sample. Criteria for enrollment, recruitment strategies, demographic information and zygosity assignment are explained for each sample. In addition, 8 studies in which CTR twins have participated are highlighted. These include studies of early cognition, early reading ability, executive cognitive function, and vulnerability to substance abuse and antisocial behavior. Goals, measures, and brief results are provided for each study. The development of the CTR is an ongoing and evolving process, and it has proved to be a valuable resource, relatively representative of the population from which it was drawn.

Important genetic influence on intervertebral disc degeneration has been shown previously. However, the role of the disc in pain production is not clear and the genetic influence on the development of the symptoms of low back pain is largely unknown. Therefore, data on lifetime prevalence of low back pain from the young cohort in The Danish Twin Registry (aged 12–41) were analyzed with respect to heredity. Casewise concordance rates, odds ratios, tetrachoric correlation coefficients and biometric liability models were estimated in relation to gender and age. Finally, age-adjusted heritability of liability estimates were obtained. Both concordance rates and odds ratios show significant genetic influence on the liability to develop low back pain. Also, tetrachoric correlation coefficients show gnetic influence, but this is not statistically significant for all age groups. The biometric modeling demonstrates shared environment to be a strong component in the youngest age group (12–15), but not above age 15, and it also demonstrates some non-additive genetic effects in the older age groups. Age-adjusted heritability of liability is estimated to 44% (37–50) for males and 40% (34–46) for females aged 16 to 41. Thus, the various analyses all demonstrate significant genetic influence on the liability to low back pain. The shared environment is an important component until age 15. After age 15, this component is unimportant. As people grow older, the effect of the non-shared environment increases and non-additive genetic effects become more evident, indicating an increasing degree of genetic interaction as age increases.

We compared twins to their gender-matched singleton classmates in peer-assessed behavioral adjustment. Our samples include 1874 11- to 12-year-old Finnish twins (687 monozygotic, MZ; 610 same-sex dizygotic, SSDZ; 577 opposite-sex dizygotic, OSDZ) and their 23,200 non-twin classmates. Data were collected using a 30-item Multidimensional Peer Nomination Inventory containing three factors and their subscales. We found twin-singleton differences: classmates rated twin girls and boys higher than gender-matched singletons in Adaptive Behaviors (constructive, compliant, and socially active behavior), and those effects were particularly evident among OSDZ twins for assessments of social interaction, popularity, and leadership. We found no evidence that individual twins differ from singletons in Externalizing (hyperactivity- impulsivity, inattention, aggression) or Internalizing Problem Behaviors (depressive symptoms, social anxiety). Nor did we find systematic differences between MZ and SSDZ twins. Among both twins and singletons, boys exceeded girls in Externalizing, and girls exceeded boys in Internalizing Problem Behaviors. Results suggest that a twinship forms a positive developmental environment for socioemotional behavior, particularly among OSDZ twins.

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.

The Enrichment Study (ES) was designed to extend the Minnesota Twin Family Study (MTFS) by oversampling 11-year-old twins at especially high risk for substance use disorders by virtue of having a childhood disruptive disorder. The sample was ascertained from Minnesota birth records. To identify high-risk twins, we conducted telephone screening interviews for parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as indications of academic disengagement. Twins who exceeded a predetermined threshold were invited to participate. To facilitate comparison with the previously ascertained MTFS participants, a random sample of 11-year-old twins was also recruited. As part of the ES study, 499 twin pairs, and their parents, visited the University of Minnesota, where each participant completed a clinical interview, psychophysiological evaluation, and thorough assessment of environmental risk. We were highly successful in recruiting at-risk twins; 52% of the screened male twins and 41% of the screened females met criteria for a diagnosis of ADHD, CD, or oppositional defiant disorder (ODD). At the pair level, 63% of the screened pairs had at least one member with a childhood disruptive disorder. This article provides an overview of the study design and includes a review of recent findings using this sample of twins.

Information on personality, on anxiety and depression and on several aspects of religion was collected in 1974 Dutch families consisting of adolescent and young adult twins and their parents. Analyses of these data showed that differences between individuals in religious upbringing, in religious affiliation and in participation in church activities are not influenced by genetic factors. The familial resemblance for different aspects of religion is high, but can be explained entirely by environmental influences common to family members. Shared genes do not contribute to familial resemblances in religion. The absence of genetic influences on variation in several dimensions of religion is in contrast to findings of genetic influences on a large number of other traits that were studied in these twin families. Differences in religious background are associated with differences in personality, especially in Sensation Seeking. Subjects with a religious upbringing, who are currently religious and who engage in church activities score lower on the scales of the Sensation Seeking Questionnaire. The most pronounced effect is on the Disinhibition scale. The resemblances between twins for the Disinhibition scale differ according to their religious upbringing. Receiving a religious upbringing seems to reduce the influence of genetic factors on Disinhibition, especially in males.

The Swedish Twin study of CHild and Adolescent Development (TCHAD) is a longitudinal study of how genes and environments contribute to development of health and behavioral problems from childhood to adulthood. The study includes 1480 twin pairs followed since 1994, when the twins were 8 to 9 years old. The last data collection was in 2005 when the twins were 19 to 20 years old. Both parents and twins have provided data. In this article we describe the sample, data collections, and measures used. In addition, we provide some key findings from the study, focusing on antisocial behavior, criminality, and psychopathic personality.

The purpose of the present study was to determine if a general factor of personality (GFP) could be extracted from the six dimensions of the HEXACO model and four factors of trait emotional intelligence. Participants were 1,192 pairs of twins (666 MZ pairs, 526 DZ pairs) between the ages of 19 to 86 years, who completed the Trait Emotional Intelligence Questionnaire — Short Form and the HEXACO Personality Inventory — Revised. Principal components analysis yielded a strong GFP accounting for 33% of the variance, on which all variables with the exception of honesty-humility from the HEXACO showed moderate to large loadings. Behavioral genetic (BG) analyses revealed that individual differences in the GFP were entirely attributable to additive genetic and non-shared environmental factors — results that are in accord with previous BG analyses of a GFP. The present study adds to the body of evidence in support of a heritable GFP but an alternative perspective is also discussed.