To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The Murcia Twin Registry (MTR) is the only population-based registry in Spain. Created in 2006, the registry has been growing more than a decade to become one of the references for twin research in the Mediterranean region. The MTR database currently comprises 3545 adult participants born between 1940 and 1977. It also holds a recently launched satellite registry of university students (N = 204). Along five waves of data collection, the registry has gathered questionnaire and anthropometric data, as well as biological samples. The MTR keeps its main research focus on health and health-related behaviors from a public health perspective. This includes lifestyle, health promotion, quality of life or environmental conditions. Future short-term development points to the expansion of the biobank and the continuation of the collection of longitudinal data.
It has been over 5 years since the last special issue of Twin Research and Human Genetics on ‘Twin Registries Worldwide: An Important Resource for Scientific Research’ was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.
Determining (1) the direction of causation and (2) the size of causal effects between two constructs is a central challenge of the scientific study of humans. In the early 1990s, researchers in behavioral genetics invented what was termed the direction of causation (DoC) model to address exactly these two concerns. The model claims that for any two traits whose mode of inheritance is sufficiently different, the direction of causation can be ascertained using a sufficiently large genetically informative sample. Using a series of simulation studies, we demonstrate a major challenge to the DoC model, namely that it is extremely sensitive to even tiny amounts of non-shared confounding. Even under ideal conditions for the DoC model (a large sample, N = 10,000), a large causal relationship (e.g., a causal correlation of .50) with very different modes of inheritance between the two traits (e.g., a pure AE model for one trait and a pure CE model for another trait) and a modest degree (correlation of .10) of non-shared confounding between the two traits results in the choice of the wrong causal models and estimating the wrong causal effects.
Psychological distress (PSYCH), somatic distress (SOMA), affective disorders (AD), and substance use (SU) frequently co-occur. The genetic relationship between PSYCH and SOMA, however, remains understudied. We examined the genetic and environmental influences on these two disorders and their comorbid AD and SU using structural equation modeling. Self-reported PSYCH and SOMA were measured in 1,548 twins using the two subscales of a 12-item questionnaire, the Somatic and Psychological Health Report. Its reliability and psychometric properties were examined. Six ADs, involvement of licit and illicit substance, and two SU disorders were obtained from 1,663–2,132 twins using the World Mental Health Composite International Diagnostic Interview and/or from an online adaption of the same. SU phenotypes (heritability: 49–79%) were found to be more heritable than the affective disorder phenotypes (heritability: 32–42%), SOMA (heritability: 25%), and PSYCH (heritability: 23%). We fit separate non-parametric item response theory models for PSYCH, SOMA, AD, and SU. The IRT scores were used as the refined phenotypes for fitting multivariate genetic models. The best-fitting model showed the similar amount of genetic overlap between PSYCH–AD (genetic correlation rG = 0.49) and SOMA–AD (rG =0.53), as well as between PSYCH–SU (rG = 0.23) and SOMA–SU (rG = 0.25). Unique environmental factors explained 53% to 76% of the variance in each of these four phenotypes, whereas additive genetic factors explained 17% to 46% of the variance. The covariance between the four phenotypes was largely explained by unique environmental factors. Common genetic factor had a significant influence on all the four phenotypes, but they explained a moderate portion of the covariance.
Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the ‘peas in the pod’ questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.
Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.
Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a “chicken-and-egg” question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.
Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness.
The analysis sample included 24 436 twins aged 40–90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms.
Women reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2 s.d. above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness.
Findings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.
One salient characteristic of twin studies and the related behavioral genetics paradigm is the requirement of a large sample size. Countries or regions that are large in size and highly populated are at an advantage when implementing twin studies. However, given the fascinating and promising results obtained from twin studies, many researchers based in smaller countries or regions may still want to conduct twin studies in order to address local and theoretical issues. In this article, we have outlined the development of twin studies in Hong Kong, one of the Special Administrative Regions of China. The historical development and design of the two major twin studies of language and reading development implemented within Hong Kong are discussed, providing insights to researchers who also aspire to conduct twin studies in small regions.
The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.
The German twin family study ‘TwinLife’ was designed to enhance our understanding of the development of social inequalities over the life course. The interdisciplinary project investigates mechanisms of social inequalities across the lifespan by taking into account psychological as well as social mechanisms, and their genetic origin as well as the interaction and covariation between these factors. Main characteristics of the study are: (1) a multidimensional perspective on social inequalities, (2) the assessment of developmental trajectories in childhood, adolescence, and young adulthood in a longitudinal design by using (3) a combination of a multi-cohort cross-sequential and an extended twin family design, while (4) capturing a large variation of behavioral and environmental factors in a representative sample of about 4,000 German twin families. In the present article, we first introduce the theoretical and empirical background of the TwinLife study, and second, describe the design, content, and implementation of TwinLife. Since the data will be made available as scientific use file, we also illustrate research possibilities provided by this project to the scientific community.
Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs.
A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress–tension. We applied a recently developed twin regression methodology – Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) – to test for evidence consistent with the existence of ‘causal’ influences between the DASS factors.
There was evidence consistent with the stress–tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001).
Our findings suggest a critical role for stress–tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.
It is unknown whether influences of midlife whole diet on the long-term CHD mortality risk are independent of genetic and common environmental factors or familial predisposition. We addressed this question prospectively using data from the National Heart, Lung, and Blood Institute Twin Study. We included 910 male twins who were middle-aged and had usual diet assessed with nutritionist-administered, cross-checked dietary history interview at baseline (1969–1973). Moderation-quantified healthy diet (MQHD), a dietary pattern, was created to evaluate a whole diet. Primary outcome was time-to-CHD death. Hazard ratios (HR) were estimated using frailty survival model. Known CHD risk factors were controlled. During the follow-up of 40 years through 31 December 2009, 113 CHD deaths, 198 total cardiovascular deaths and 610 all-cause deaths occurred. In the entire cohort, the multivariable-adjusted HR for the overall association (equivalent to a general population association) was 0·76 (95 % CI 0·66, 0·88) per 10-unit increment in the MQHD score for CHD, and the multivariable-adjusted HR for a twin with a MQHD score ten units higher than his co-twin brother was 0·79 (95 % CI 0·64, 0·96, P=0·02) for CHD independent of familial predisposition. Similar results were found for a slightly more food-specified alternative moderation-quantified healthy diet (aMQHD). The between-pair association (reflecting familial influence) was significant for CHD for both MQHD and aMQHD. It is concluded that associations of MQHD and aMQHD with a lower long-term CHD mortality risk are both nutritionally and familially affected, supporting their use for dietary planning to prevent CHD mortality.
Little is known about the extent to which aging trajectories of different body systems share common sources of variance. We here present a large twin study investigating the trajectories of change in five systems: cardiovascular, respiratory, skeletal, morphometric, and metabolic. Longitudinal clinical data were collected on 3,508 female twins in the TwinsUK registry (complete pairs:740 monozygotic (MZ), 986 dizygotic (DZ), mean age at entry 48.9 ± 10.4, range 18–75 years; mean follow-up 10.2 ± 2.8 years, range 4–17.8 years). Panel data on multiple age-related variables were used to estimate biological ages for each individual at each time point, in linear mixed effects models. A weighted average approach was used to combine variables within predefined body system groups. Aging trajectories for each system in each individual were then constructed using linear modeling. Multivariate structural equation modeling of these aging trajectories showed low genetic effects (heritability), ranging from 2% in metabolic aging to 22% in cardiovascular aging. However, we found a significant effect of shared environmental factors on the variations in aging trajectories in cardiovascular (54%), skeletal (34%), morphometric (53%), and metabolic systems (53%). The remainder was due to environmental factors unique to each individual plus error. Multivariate Cholesky decomposition showed that among aging trajectories for various body systems there were significant and substantial correlations between the unique environmental latent factors as well as shared environmental factors. However, there was no evidence for a single common factor for aging. This study, the first of its kind in aging, suggests that diverse organ systems share non-genetic sources of variance for aging trajectories. Confirmatory studies are needed using population-based twin cohorts and alternative methods of handling missing data.
Approximately 60% of children with reading difficulties (RD) meet criteria for at least one co-occurring disorder. The most common of these, attention deficit-hyperactivity disorder (ADHD), occurs in 20–40% of individuals with RD. Recent studies have suggested that genetic influences are responsible. To assess the genetic etiologies of RD and the comorbidity of RD and two ADHD symptom dimensions –– inattention (IN) and hyperactivity/impulsivity (H/I) –– we are conducting the first longitudinal twin study of RD and ADHD. Data from twin pairs in which at least one member of the pair met criteria for proband status for RD at initial assessment, and were reassessed 5 years later, were subjected to DeFries-Fulker (DF) analysis. Analyses of reading composite data indicated that over 60% of the proband deficit at initial assessment was due to genetic influences, and that reading deficits at follow-up were due substantially to the same genetic influences. When a bivariate DF model was fitted to reading performance and IN data, genetic influences accounted for 60% of contemporaneous comorbidity and over 60% of the longitudinal relationship. In contrast, analysis of the comorbidity between reading performance and H/I indicated that common genetic influences accounted for only about 20% of the contemporaneous and about 10% of the longitudinal relationships. Results indicate that (1) genetic influences on RD are substantial and highly stable; (2) the comorbidity between RD and IN is due largely to genetic influences, both contemporaneously and longitudinally; and (3) genetic influences contribute significantly less to the comorbidity between RD and H/I.
The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability.
AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits.
For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2.
Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes.
Mixed anxiety–depression (MAD) has been under scrutiny to determine its potential place in psychiatric nosology. The current study sought to investigate its prevalence, clinical characteristics, course and potential validators.
Restricted latent-class analyses were fit to 12-month self-reports of depression and anxiety symptom criteria in a large population-based sample of twins. Classes were examined across an array of relevant indicators (demographics, co-morbidity, adverse life events, clinical significance and twin concordance). Longitudinal analyses investigated the stability of, and transitions between, these classes for two time periods approximately 1.5 years apart.
In all analyses, a class exhibiting levels of MAD symptomatology distinctly above the unaffected subjects yet having low prevalence of either major depression (MD) or generalized anxiety disorder (GAD) was identified. A restricted four-class model, constraining two classes to have no prior disorder history to distinguish residual or recurrent symptoms from new onsets in the last year, provided an interpretable classification: two groups with no prior history that were unaffected or had MAD and two with prior history having relatively low or high symptom levels. Prevalence of MAD was substantial (9–11%), and subjects with MAD differed quantitatively but not qualitatively from those with lifetime MD or GAD across the clinical validators examined.
Our findings suggest that MAD is a commonly occurring, identifiable syndromal subtype that warrants further study and consideration for inclusion in future nosologic systems.
Obesity is a substantial health problem in the United States, and is associated with many chronic diseases. Previous studies have linked poor dietary habits to obesity. This cross-sectional study aimed to identify the association between body mass index (BMI) and fast-food consumption among 669 same-sex adult twin pairs residing in the Puget Sound region around Seattle, Washington. We calculated twin-pair correlations for BMI and fast-food consumption. We next regressed BMI on fast-food consumption using generalized estimating equations (GEE), and finally estimated the within-pair difference in BMI associated with a difference in fast-food consumption, which controls for all potential genetic and environment characteristics shared between twins within a pair. Twin-pair correlations for fast-food consumption were similar for identical (monozygotic; MZ) and fraternal (dizygotic; DZ) twins, but were substantially higher in MZ than DZ twins for BMI. In the unadjusted GEE model, greater fast-food consumption was associated with larger BMI. For twin pairs overall, and for MZ twins, there was no association between within-pair differences in fast-food consumption and BMI in any model. In contrast, there was a significant association between within-pair differences in fast-food consumption and BMI among DZ twins, suggesting that genetic factors play a role in the observed association. Thus, although variance in fast-food consumption itself is largely driven by environmental factors, the overall association between this specific eating behavior and BMI is largely due to genetic factors.
Twins reared apart provide a fascinating experiment to distinguish genetic from environmental influences. However, there is as yet no broad report on distribution of twins reared apart, especially in the Chinese population. In this study, information on 18,295 volunteer twin pairs of all age groups was compiled in nine provinces or cities of China, and questionnaires were used for zygosity determination. It was discovered that twins reared apart from 0 to 10 years of age accounted for 2.2% of all twin interviewees, with the proportion of this 0–10 group separated before 1, 2, and 5 years old, accounting for 65.3%, 76.1%, and 91.3%, respectively. The proportion of twins reared apart is not significantly related to zygosity or gender, but it is related to region and twin age. As the age of twins lowers, the proportion of those reared apart gradually decreases. Twins reared apart will become rarer in the future and therefore should be cherished as a resource.
In many Western countries, women now reach educational levels comparable to men, although their income remains considerably lower. For the past decades, it has become increasingly clear that these measures of socio-economic status are influenced by genetic as well as environmental factors. Less is known about the relationship between education and income, and sex differences. The aim of this study was to explore genetic and environmental factors influencing education and income in a large cohort of young Norwegian twins, with special emphasis on gender differences. National register data on educational level and income were obtained for 7,710 twins (aged 29–41 years). Bivariate Cholesky models were applied to estimate qualitative and quantitative gender differences in genetic and environmental influences, the relative contribution of genetic and environmental factors to the correlation between education and income, and genetic correlations within and between sexes and phenotypes. The phenotypic correlation between educational level and income was 0.34 (0.32–0.39) for men and 0.45 (0.43–0.48) for women. An ACE model with both qualitative and quantitative sex differences fitted the data best. The genetic correlation between men and women (rg) was 0.66 (0.22–1.00) for educational attainment and 0.38 (0.01–0.75) for income, and between the two phenotypes 0.31 (0.08–0.52) for men and 0.72 (0.64–0.85) for women. Our results imply that, in relatively egalitarian societies with state-supported access to higher education and political awareness of gender equality, genetic factors may play an important role in explaining sex differences in the relationship between education and income.