Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent upon situational factors. We aimed to decompose EA into influences attributable to genetic propensity and to environmental context and their interplay, while considering influences of rearing household economic status (HES) and sex. We use the Project Talent Twin and Sibling Study, drawn from the population-representative cohort of high school students assessed in 1960 and followed through 2014, to ages 68−72. Data from 3552 twins and siblings from 1741 families were analyzed using multilevel regression and multiple group structural equation models. Individuals from less-advantaged backgrounds had lower EA and less variation. Genetic variance accounted for 51% of the total variance, but within women and men, 40% and 58% of the total variance respectively. Men had stable genetic variance on EA across all HES strata, whereas high HES women showed the same level of genetic influence as men, and lower HES women had constrained genetic influence on EA. Unexpectedly, middle HES women showed the largest constraints in genetic influence on EA. Shared family environment appears to make an outsized contribution to greater variability for women in this middle stratum and whether they pursue more EA. Implications are that without considering early life opportunity, genetic studies on education may mischaracterize sex differences because education reflects different degrees of genetic and environmental influences for women and men.

The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942–1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9–12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the ‘common’ environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960–1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68–72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917–1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson’s disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from over 17,500 participants aged 25–102 at baseline (including nearly 2,600 monogygotic and 4,300 dizygotic twin pairs and over 1,700 family members) aims to understand why early life adversity, and social factors such as isolation and loneliness, are associated with diverse outcomes including mortality, physical functioning (health, functional ability), and psychological functioning (well-being, cognition), particularly in later life.

The Study of Dementia in Swedish Twins is a study of dementia in a defined population of twins. The goals included estimating heritability of Alzheimer's disease and identifying risk and protective factors in twin pairs discordant for the disease. The data, including not only diagnoses and age of onset but also extensive information about potential environmental risk factors, are now archived as Study ICPSR 25963 at National Archive for Computerized Data on Aging, Inter-university Consortium for Political and Social Research, at the University of Michigan, and available for researchers to use. Up to the time of archiving, 215 cases of dementia have been identified from a base sample of 2,394 individuals.

The nature of Generalized Anxiety Disorder (GAD) and worry across the lifespan remains incompletely understood. We investigated genetic and environmental influences on GAD and the proportion of genetic and environmental variation in GAD that is shared with neuroticism in older adult twins. Participants included 1618 monozygotic and 2291 same-sexed dizygotic twin pairs from the Swedish Twin Registry aged 55 to 74. Participants provided personality information in 1973 and also participated in a telephone screening between 1998 and 2002 that included an assessment for lifetime GAD. Univariate biometric models indicated that both GAD and neuroticism were moderately heritable (.27 and .47, respectively), while the balance of variation reflected environmental factors unique to the individual. Bivariate analyses indicated that approximately one third of the genetic influences on GAD were in common with genetic influences on neuroticism, while individual specific environmental influences were virtually unshared between GAD and neuroticism. Analyses of sex effects suggested that men and women differed in the frequency of lifetime GAD and level of neuroticism; however, no sex differences for genetic and environmental influences for either trait were identified.

We investigated the extent to which cognitive dysfunction is shaped by genetic or environmental influences, and whether these factors differ in women and men. All members of the Swedish Twin Registry aged 65 and older were screened by telephone using the TELE, a brief cognitive assessment instrument (Gatz et al., 2002), and the Blessed Dementia Rating Scale (Blessed et al., 1968) from relatives of those who scored poorly on the TELE. Data were available for 4308 pairs where both members responded and 5070 pairs where only one member was alive and participated. To analyze all available data, we used a raw data method extended to ordinal data. As the prevalence of cognitive dysfunction increases with age, we incorporated age-adjusted thresholds. The best fitting model from biometric analyses indicated 35% of the variation in liability to cognitive dysfunction could be explained by heritable influences and the remaining 65% by nonfamilial environmental influences. Differences by gender were not significant. As this is a normative population including cognitively intact individuals, preclinical dementia cases and demented individuals, the relative magnitude of genetic and environmental effects is of particular interest in light of high heritabilities found for dementias such as Alzheimer's disease. The findings emphasize the extent to which research is needed to uncover nonfamilial environmental influences on cognitive dysfunction in later life.

The Swedish Twin Registry was first established in the late 1950s. Today it includes more than 170,000 twins — in principle all twins born in Sweden since 1886. In this article we describe some ongoing and recently completed projects based on the registry. In particular, we describe recent efforts to screen all twins born between 1959 and 1985, and young twin pairs when they turn 9 and 12 years of age. For these studies, we present initial frequencies of common conditions and exposures.

The possibility of genotype–environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype–nonshared environment interactions. Multiple ‘variability genes’ were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2A and 5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to ‘contextualize’ the possible nonshared environmental influences for found gene–environment (G × E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G × E relationship observed for ESR1 and APOE and longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors.

In studies that employ matched pair analysis to identify environmental exposures important for a disorder, criteria for discordant pairs are seldom discussed. Yet several assumptions concerning the definition of discordancy may have considerable influence over what results are found. Problems are exacerbated when age of onset for a disorder is late in life. We propose a new set of criteria for defining discordant pairs in studies of dementia, taking into account duration of discordance and competing causes of mortality, and evaluate the consequences of choosing alternative definitions of discordancy. Twin Research (2000) 3, 159–164.

Twins are sometimes used as proxy informants but little is known about reliability and validity of the information thus obtained. The present study asks: (1) to what extent do twin pairs agree with each other on comparative ratings of health, psychosocial traits, and environmental exposures?; and (2) how well do comparative ratings agree with usual self-reported information about the exposures? Using 55 monozygotic (MZ) and 71 dizygotic (DZ) same-sex pairs reared together, percentage agreement was calculated for 44 comparative ratings. Pairs agreed on average about half of the time. Agreement was higher for more discrete exposures, such as smoking, but lower for more subjective variables, such as the degree to which life is experienced as stressful. Signed rank tests were used to contrast comparative ratings to differences in self- reports. Differences between twin partners in their self-report indices, where available, were in the direction suggested by the comparative rating. Comparative ratings appear most accurate for smoking and alcohol use, and less consistent for mental health symptoms and self-rated health.

Background. Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD.

Method. Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998–2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972–1973.

Results. In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1·00 in females and +0·74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0·59 in males and +0·36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD.

Conclusion. Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.

Background: Both anxiety disorders and subclinical anxiety symptoms are related to poorer health and functioning in later life. Because worry is an important component of anxiety, the accurate measurement of worry is crucial to studying the etiology, prevention and treatment of anxiety disorders. Assessment of the trait worry has emerged as the most widely used strategy to establish the presence and extent of pathological worry. However, the Penn State Worry Questionnaire (PSWQ), the most widely used measure of the trait worry, has not been validated cross-culturally in groups outside of the U.S.A.

Methods: We tested the psychometric properties and measurement invariance of an 8 item abbreviated version of the PSWQ (PSWQ-A) in American (N = 206) and Spanish (N = 137) older adult samples.

Results: Internal consistency was high and analyses supported a unidimensional solution in both samples. Measurement invariance was tested using confirmatory factor analysis (CFA) and Rasch models. Results of the CFA suggest that measurement invariance between the samples can be assumed for women but not for men. Rasch modeling results by gender suggested that three items have different endorsability levels in the two samples, suggesting that certain items may more closely represent the construct of the trait worry in American and Spanish older adults.

Conclusions: Overall, the PSWQ-A appears appropriate for cross-cultural use, although deletion of one item (item 6) may improve the psychometric properties of the scale across different populations.

We explored the effect of education and occupational complexity on the rate of cognitive decline (as measured by the Mini-Mental State Examination) in 171 patients with a confirmed Alzheimer's disease (AD) diagnosis. Complexity was measured as substantive complexity of work and complexity of work with data, people, and things. Average lifetime occupational complexity was calculated based on years at each occupation. Participants were followed for an average of 2.5 years and 3.7 visits. In multivariate mixed-effects models, high education, high substantive complexity, and high complexity of work with data and people predicted faster rates of cognitive decline, controlling for age, gender, native language, dementia severity, and entry into the analyses at initial versus follow-up testing. These results provide support for the concept of cognitive reserve according to which greater reserve may postpone clinical onset of AD but also accelerate cognitive decline after the onset. (JINS, 2006, 12, 147–152.)

Background. In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD).

Method. Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models.

Results. Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to ~35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD.

Conclusion. In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.

Background: The purpose of this study was to examine if Type 2 diabetes mellitus is a risk factor for dementia in very old age, specifically for Alzheimer's disease (AD) and vascular dementia (VaD). Methods: We evaluated the risk of dementia in relation to Type 2 diabetes using a population-based sample of 702 individuals aged 80 years and older (mean age 83 years). A total of 187 persons received a dementia diagnosis. Thirty-one individuals had a diabetes diagnosis prior to onset of the dementia. Results: Cox proportional hazard analyses, adjusted for age, gender, education, smoking habits, and circulatory diseases, indicated an elevated risk to develop VaD (relative risk = 2.54, 95% confidence interval 1.35–4.78) in individuals with diabetes mellitus. No association was found between diabetes and AD. Conclusion: Type 2 diabetes is selectively related to the different subtypes of dementia. There is no increased risk of AD but more than a twofold risk of VaD in persons with diabetes.