We recently showed that the correlation of gray and white matter volume with full scale IQ and the Working Memory dimension are completely mediated by common genetic factors (Posthuma et al., 2002). Here we examine whether the other WAIS III dimensions (Verbal Comprehension, Perceptual Organization, Processing Speed) are also related to gray and white matter volume, and whether any of the dimensions are related to cerebellar volume. Two overlapping samples provided 135 subjects from 60 extended twin families for whom both MRI scans and WAIS III data were available. All three brain volumes are related to Working Memory capacity (r = 0.27). This phenotypic correlation is completely due to a common underlying genetic factor. Processing Speed was genetically related to white matter volume (rg = 0.39). Perceptual Organization was both genetically (rg = 0.39) and environmentally (re= −0.71) related to cerebellar volume. Verbal Comprehension was not related to any of the three brain volumes. It is concluded that brain volumes are genetically related to intelligence which suggests that genes that influence brain volume may also be important for intelligence. It is also noted however, that the direction of causation (i.e., do genes influence brain volume which in turn influences intelligence, or alternatively, do genes influence intelligence which in turn influences brain volume), or the presence or absence of pleiotropy has not been resolved yet.

Combat-related posttraumatic stress disorder (PTSD) is highly comorbid with other mental disorders. However, the nature of the relationship between PTSD and other mental disorders remains unclear. A discordant high-risk twin design was used on data from a sub-sample of the male-male twin pair members of the Vietnam Era Twin Registry to examine whether patterns of comorbidity are consistent with a psychopathological response to combat exposure or reflect familial vulnerability to psychopathology. Mental disorders were assessed via the Mental Health Diagnostic Interview Schedule Version III — Revised. Discordant monozygotic within-pair comparisons revealed that PTSD probands had higher symptom counts and diagnostic prevalences of mood and anxiety disorders than their non-combat exposed co-twins. Monozygotic co-twins of PTSD probands had significantly more mood disorder symptoms than monozygotic co-twins of combat controls or dizygotic co-twins of veterans with PTSD. These findings suggest that a) major depression, generalized anxiety disorder and panic disorder are part of a post-combat response syndrome; b) a shared familial vulnerability also contributes to the association between PTSD and major depression, PTSD and dysthymia, and c) this shared vulnerability is mediated by genetic factors.

The identification of genetic factors that confer susceptibility to the epilepsies has to date been the focus of genetic efforts in this field. Few studies have assessed the genetic contribution to disease course in epilepsy, yet an understanding of the genetic influences on epilepsy outcome is key to developing new therapeutic strategies. The aim of this study was to assess the genetic contributions to epilepsy outcome in twin pairs concordant for epilepsy. We studied 37 epilepsy concordant twin pairs (27 monozygotic, 10 dizygotic) in whom there were no recognized environmental contributions (e.g., acquired brain injury) to epilepsy, and in whom the most likely cause for epilepsy was a shared genetic susceptibility. Clinical outcome was determined using the binary measure of Seizure Status (seizure remission or recurrence) and on a six-category ordinal Outcome Scale. Epilepsy outcome was independent of age of seizure onset, age at assessment and major epilepsy syndrome diagnosis. The proportion of twin pairs concordant for Seizure Status was 0.81 (22/27) for monozygous and 1.0 (10/10) for dizygous pairs, p = 0.3. Within-pair correlation in outcome (Outcome Scale) was 0.60 (95% CI: 0.32, 0.78) in monozygous and 0.78 (0.48, 0.92) in dizygous pairs. These data provide no evidence for genetic influences on epilepsy outcome independent of those that contribute to disease susceptibility. The observed high correlations for outcome suggest that, for epilepsy, susceptibility genes also have a major influence on outcome.

Using a longitudinal twin study of Moscow children, we have studied the development of psychometric intelligence during the transition from preschool (age 6) to school (age 7). Children were tested using the Wechsler Intelligence Scale for Children (WISC). Simplex models were applied to explore the relationship of different sources of phenotypic variance. The following sources of variation were considered: genetic effects, common or shared family environment and unique environment. At age 6, genetic influences were much greater than those of shared environment but the magnitude of genetic influences decreased and the magnitude of shared environment influences increased substantially by age 7.

Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20–29 and 30–39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.

The authors define a trait “wellness” for good health in 6109 men in the National Academy of Sciences-National Research (NAS-NRC) twin panel aged 70 years and up surveyed by mail in the fall of 1998. Men who responded that they had not had a heart attack, coronary surgery, stroke, diabetes or prostate cancer in the survey questionnaire (Q8) met the broad definition of wellness. A more narrow definition included the absence of hypertension. Genetic analysis indicated that over 50% of the population variance for liability to either wellness definition was genetic. A subset of the NASNRC twins also participates in the National Heart, Lung and Blood Institute (NHLBI) twin study. NHLBI examinations and medical record review was done in 1986–1987 and 1995–1997 for 389 individuals who completed Q8. Excellent agreement (kappa > 0.8) was found between Q8 and outcome review for each condition comprising the wellness definition, ranging from 0.81 for coronary surgery to 0.88 for diabetes. Substantial agreement (kappa = 0.67) was found for hypertension. Kappa values for wellness were 0.82 for the broader definition and 0.74 if high blood pressure was included. Fraternal twin-pairs concordant for the wellness definitions are currently being recruited for linkage studies.

The study examines the effects of being born small for gestational age (SGA) on rates of behavioral problems in twins and siblings, utilising data from the Australian Twin Study of disruptive behavior disorders in twins and their siblings. Participants were 3944 twins and their siblings who were assessed at two intervals three years apart. At the first assessment (1991), they ranged between 4 and 12 years of age. Items assessing Attention Deficit /Hyperactivity Disorder were based on DSM-III-R criteria (Time 1) and DSM-IV criteria (Time 2). Other measures included history of speech and reading therapy, demographic information and obstetric and neonatal history. Results indicated that both male and female twins, who were extremely growth restricted (small for gestational age up to the third percentile—WGA3) showed more inattention, and poorer speech and reading scores. The effects were greater for males. Male twins who were small for gestation age, up to the 10th percentile, were more likely to have a DSM-IV diagnosis of Inattention. Implications of these results included WGA3 male twins being at a “triple disadvantage” for subsequent behavioral and learning problems, in that being male, being a twin and being small for gestational age are all significant factors. Recommendations are made for early intervention for low birthweight male twins. The study is consistent with recent follow-up studies of very-low-birthweight singletons, indicating male disadvantage in cognitive outcome. While there is some genetic component to SGA, it does constitute a potentially major contribution to common environmental effects that must be considered in twin-based genetic analyses.

High rates of twinning have been reported in Africa. This study sought to learn whether mothers of twins experience different stress levels than those who have only singletons. Both twin mothers (101) and singleton mothers (101) were interviewed. Using a scale of 15 stressors the researchers found that the mean stress score was significantly higher for twin mothers than singleton mothers. Higher stress scores were also associated with parity and perceptions of problems in caring for children and inversely related to perceived levels of social support. Confronting stressors or simply accepting them were the two main ways that mothers coped with their problems.

Population and total hip replacement surveys show that primary osteoarthritis of the hip is uncommon in African Americans and rare in Asians, suggesting a genetic basis for this disease. We studied genetic influences on primary osteoarthritis of the hip by estimating monozygotic (MZ) and dizygotic (DZ) twin correlations using a two-stage data collection. A total of 6419 male veteran twins of the NAS-NRC Twin Registry, born between 1917 and 1927, were contacted by telephone (first stage). Telephone interview determined that 2% reported a total hip replacement for arthritis rather than fracture. X-rays of twin pairs in which one twin had undergone total hip replacement were sought and reviewed (second stage), and concordance for primary arthritis was determined based on x-ray diagnosis. Heritability of primary osteoarthritis, Kellgren & Lawrence Grade II and higher, was estimated using a covariance structure analysis for 2-stage data. The best-fitting model included only components for additive genetics and for unique environment. Additive genetics accounted for 53% (95% confidence interval 30–72%) in the liability for self reported hip replacement surgery and unique environment for the remaining 47% (95% confidence interval 28–70%). Additive genetics accounted for 61% (95% confidence interval 18-86%) of the variance in liability for x-ray determined primary osteoarthritis with unique environment accounting for the remaining 39%. These data establish a genetic influence on primary osteoarthritis of the hip in male twins and suggest that further work is indicated to isolate the genes responsible for this disease.

The purpose of the present study was to clarify genetic and environmental origins of psychological traits of eating disorders using a Japanese female twin sample. Participants were 162 pairs of female twins consisting of 116 pairs of monozygotic (MZ) twins and 46 pairs of dizygotic (DZ) twins in their adolescence. Psychological traits of eating disorders were assessed with five subscales of the Eating Disorder Inventory (EDI). As a result of using univariate twin analyses, among five subscales of EDI (maturity fears, ineffectiveness, interpersonal distrust, interoceptive awareness, and perfectionism), perfectionism showed significant additive genetic contributions and individual specific environmental effects. On the other hand, maturity fears, ineffectiveness, interoceptive awareness, and interpersonal distrust indicated significant shared environment contributions and individual specific environment effects. The results suggest the importance of both genetic and shared environmental influences on psychological traits of eating disorders in the present study.

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

Most analyses of data collected from a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins assume that zygosity has been diagnosed without error. However, large scale surveys frequently resort to questionnaire-based methods of diagnosis which classify twins as MZ or DZ with less than perfect accuracy. This article describes a mixture distribution approach to the analysis of twin data when zygosity is not perfectly diagnosed. Estimates of diagnostic accuracy are used to weight the likelihood of the data according to the probability that any given pair is either MZ or DZ. The performance of this method is compared to fully accurate diagnosis, and to the analysis of samples that include some misclassified pairs. Conventional analysis of samples containing misclassified pairs yields biased estimates of variance components, such that additive genetic variance (A) is underestimated while common environment (C) and specific environment (E) components are overestimated. The bias is non-trivial; for 10% misclassification, true values of Additive genetic: Common environment: Specific Environment variance components of .6: .2: .2 are estimated as .48: .29: .23, respectively. The mixture distribution yields unbiased estimates, while showing relatively little loss of statistical precision for misclassification rates of 15% or less. The method is shown to perform quite well even when no information on zygosity is available, and may be applied when pair-specific estimates of zygosity probabilities are available.

Women's mental health can be compromised during reproductive life, but to date there has been relatively little specific investigation of the links between multiple births and perinatal psychiatric illness. There has been more comprehensive examination of some of the psychological sequelae of multiple gestations and births, but many of the studies have small samples and are descriptive in nature. Most of the literature is drawn from investigations of the psychological aspects of multiple births following assisted conception. Current conceptualizations of the determinants of maternal perinatal mental health, with particular reference to multiple gestations and births are discussed and implications for clinical practice suggested.

Overall there is evidence that women with multiple gestation and multiple births may be at elevated risk for pregnancy anxiety, postpartum depression and complicated grief reactions. Much less is currently known about the associations between multiple birth and either maternity blues or postpartum psychosis. The relationships between personal or family psychiatric history, past experience of childhood abuse, intimate partner intimidation and psychological adjustment to multiple births are not known. The interactions between multiple births, operative delivery, prematurity, neonatal illness and separation of mother and infant as contributing factors to maternal postpartum mental health are not known. There is very limited evidence about the psychological functioning of fathers of multiple infants. Routine antenatal, intrapartum and postnatal health care for women with multiple infants needs to take into account the additional psychological demands they face.

Risk factors for coronary heart disease (CHD), including prethrombotic changes in hemostasis, cluster with the insulin resistance (IR) syndrome. The aim of the present study was to investigate to what extent the relation between IR and hemostatic risk factors is due to shared genes or environmental factors. Multivariate genetic analysis was performed using a total of 314 (107 monozygotic and 207 dizygotic) twin pairs on IR assessed by HOMA, fibrinogen, plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA), factor VIII (FVIII), von Willebrand factor (vWF) and factor XIII Bsubunit. The relationship between IR and the 6 hemostatic factors could best be explained by an independent pathway model consisting of 2 common genetic factors, one of which influenced IR and all hemostatic factors, and 3 common environmental factors, each representing the shared variance between IR and different aspects of the hemostatic system. Genetic correlations between IR and hemostatic proteins were larger than their environmental counterparts. Since IR and prethrombotic changes are features of both diabetes and CHD, the finding of one set of pleiotropic genes warrants the identification of these common pathways which may provide new avenues for treatment and prevention of both diabetes and CHD.

Retrospective assessment of maternal smoking or substance use during pregnancy is sometimes unavoidable. The unusually close relationship of twin sister pairs permits comparison of self-report data versus co-twin informant data on substance use during pregnancy. Information about smoking during pregnancy has been gathered from a series of mothers from an Australian volunteer twin panel (576 women reporting on 995 pregnancies), supplemented in many cases by independent ratings of their smoking by twin sister informants (821 pregnancies). Estimates of the proportion of women who had never smoked regularly (56–58%), who had smoked but did not smoke during a particular pregnancy (16–21%), or who smoked throughout the pregnancy (16–18%), were in good agreement whether based on selfreport or twin sister informant data. However, informants underreported cases who smoked during the first trimester but then quit (1–3% versus 7–9% by self-report). Women who smoked throughout pregnancy (by informant report) rarely denied a history of regular smoking (< 1%), although a small proportion of apparent false negative cases were identified where they either denied smoking during a pregnancy (9%) or denied smoking beyond the first trimester (10%). We conclude that retrospective smoking data can safely be used to identify potential associations of later child outcomes with maternal smoking during pregnancy.

Good nutrition is central to achieving optimal fetal growth and development, and to maintaining maternal health and wellbeing. For multiple pregnancies, there is a growing body of evidence linking good maternal nutrition and weight gain to positive perinatal outcomes including reduced incidence of low birthweight and very low birthweight infants. Nutrition intervention appears to have important clinical implications for infant morbidity and mortality. Nutritional counselling can help women improve and maximise their intake of “at risk nutrients” such as iron, folate, essential fatty acids, calcium and ensure adequate energy intake to meet weight gain targets. Recommended optimal weight gains range from 16–20kg for twin pregnancies. Expert dietetic guidance is often warranted, especially for women expecting triplets or quadruplets.

Age-related changes in the composition of the cartilage matrix may be associated with the development of osteoarthritis, a relatively late-onset disease characterised by the destruction of joint cartilage. In order to investigate whether differences in the VNTR polymorphic region of aggrecan affect cartilage functionality and therefore the development of osteoarthritis, we examined the aggrecan polymorphic genotypes of a sample of 134 Australian twins aged over 50 (including 34 monozygotic and 27 dizygotic twin pairs). Clinical measures of hand, hip and knee osteoarthritis, as well as self-reported bone and joint pain, were tested for association with the aggrecan polymorphism. The results were consistent with either a deleterious effect of allele 27, or a protective effect of alleles 25 and 28, providing some additional evidence for an association between the aggrecan VNTR polymorphism and osteoarthritis of the hands, hips and knees.

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.