Longitudinal Twin Data Research Articles

Development of temperament types from infancy to adolescence: Genetic and environmental influences with an economically and racially/ethnically diverse sample.

Kagan theorized biologically based temperament types that are present in infancy, stable across development, and essential for understanding individual differences. Despite evidence, temperament research remains focused on a few prominent dimensions of temperament, without adequately addressing covariance among dimensions and temperament types. Using longitudinal twin data, we took a person-centered statistical approach to identify temperament types and examined continuity and change across five developmental periods (Ninfancy = 602; Ntoddlerhood = 522; Nearly childhood = 390; Nlate childhood = 718; Nearly adolescence = 700). We then examined the genetic and environmental etiology of temperament types. Twins were boys and girls (51-53% female), primarily Hispanic/Latinx (23-30%) and non-Hispanic/Latinx White (56-63%), and from socioeconomically diverse families (28-38% near-or-below the poverty line). Using latent profile analysis, we identified three temperament types at each age characterized by negative reactivity and dysregulation, positive reactivity and strong self-regulation, and moderate reactivity and regulation. Latent transition analyses revealed considerable continuity in membership type for "negative dysregulated" beginning in infancy, log odds = 1.58 (SE = .65) to 3.16 (SE = .77), p < .01, of remaining relative to transitioning to "typical expressive", and "positive well-regulated" beginning in early childhood, log odds = 1.41 (SE = .56) to 2.25 (SE = .47), p < .05. Twin analyses revealed moderate heritability and a consistent role of the shared environment on positive well-regulated, with negative dysregulated and typical expressive also moderately heritable with the shared environment being important at some ages. Findings support the presence of theorized biologically based temperament types that develop rapidly in infancy and toddlerhood and provide a foundation for the study of individual differences and risk and resilience processes across the lifespan. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Social anxiety disorder is a risk factor for alcohol use problems in the National Comorbidity Surveys

BackgroundAccording to the self-medication and biopsychosocial models, individuals with social anxiety disorder (SAD) are at increased risk of developing an alcohol use disorder (AUD) as alcohol represents a maladaptive coping mechanism for some sufferers of SAD. The SAD-to-AUD causation was earlier supported in Norwegian longitudinal twin data and later questioned using longitudinal data from the USA. MethodsWe re-analyzed partly the same USA-based data (National Comorbidity Surveys, n = 5001), conducting theoretical and simulation analyses on different formulations of temporality and using real-data Logistic regression analysis to investigate whether baseline SAD was associated with AUD at the follow-up. ResultsUpon proper analysis of temporality, SAD preceded AUD. Specifically, SAD was the only one of the seven anxiety disorders that predicted 10-year later AUD after adjusting for all other anxiety disorders and AUD at the baseline (odds ratio was 1.70% and 95% confidence interval 1.12–2.57). SAD was also associated with incident AUD (OR = 1.64, 95% CI = 1.14–2.37). We provide formal, simulation-based, and data-based arguments on how certain flawed models of incidence attenuate the temporal association. ConclusionsWe demonstrated temporality and specificity in SAD-to-AUD association, which are considered signs of causation. We further identified and discussed problems in previous statistical analyses with different conclusions. Our findings add support for models positing causal effects of SAD on AUD, such as the self-medication and biopsychosocial models. The available evidence suggests that treating SAD should incur better chances of preventing AUD compared to treating other anxiety disorders, which lack comparable evidence on causation.

The role of pain and psychological distress in fatigue: a co-twin and within-person analysis of confounding and causal relations

ABSTRACT Objective Fatigue is a common symptom in somatic and mental illness. Musculoskeletal pain and psychological distress have in turn frequently been shown to be associated with fatigue across clinical conditions and in the general population. The study aims to disentangle direct effects from those due to mere confounding from shared etiologies. Design The study used genetically informative longitudinal twin data, through a co-twin control design with an additional within-person dimension. Methods Data on fatigue, pain and distress from 2196 mono – and dizygotic twins from the Norwegian Twin Registry examined at two time points five years apart was analyzed using multilevel generalized linear regression modeling. Fatigue was regressed on pain and distress, with further controls added for confounding from genetic and stable non-shared environmental sources. Results Pain and distress had a significant impact on fatigue at genetic, stable non-shared environmental and time-varying levels, even when controlling for somatic comorbidity. Conclusion The findings indicate that a significant proportion of the association between fatigue, pain and distress is due to genetic and environmental confounding. Pain and distress exert significant, albeit smaller effects on fatigue even when controlling for genetic and stable environmental contributions, indicating direct effects. Potential etiological pathways and underlying mechanisms are discussed.

Not Seeing Double: Discordance in Disease, Function, and Their Longitudinal Associations in Monozygotic Twins

Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being. The Twins sub-sample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (Wave 1: 1995-1996, Wave 2: 2004-2006). Only monozygotic twins (N = 713) were included in analyses. In separate multi-level models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1. Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = .40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = .06, p = .02). Well-being was not a moderator in either model. We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.

Not Seeing Double: Discordance in Disease, Function, and Their Longitudinal Associations in Monozygotic Twins.

Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being. The twin subsample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (wave 1, 1995-1996; wave 2, 2004-2006). Only monozygotic twins (n = 713) were included in analyses. In separate multilevel models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1. Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = 0.40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = 0.06, p = .02). Well-being was not a moderator in either model. We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.

Etiological pathways of depressive and anxiety symptoms linked to personality traits: A genetically-informative longitudinal study

BackgroundThe comorbidity of depression and anxiety is associated with an increased risk of prolonged adverse mental health status. However, little is currently known about their genetic and environmental influences that help to explain both the comorbidity and distinctiveness. Using longitudinal twin data, the present study investigated both the overlapping and distinct relationships between depression and anxiety viewed from the perspective of Gray's Reinforcement Sensitivity Theory (RST): two personality traits of the Behavioral Inhibition and Activation Systems (BIS and BAS). MethodsA total of 422 twin pairs (298 monozygotic and 124 dizygotic pairs) participated by completing a personality questionnaire at wave 1, and mood symptoms questionnaires at wave 2. The waves were on average 2.23 years apart. ResultsMultivariate Cholesky decomposition indicated that the genetic variance of the personality traits (BIS and BAS) explained all of the genetic variance in depressive and anxiety symptoms. Additionally, genetic factors related to the BIS positively explained depressive and anxiety symptoms, whereas genetic factors related to the BAS negatively explained only depressive symptoms. LimitationsLimitations include shorter time interval and the reliance on self-reported data. ConclusionsThe present study provided evidence explaining the overlap and differentiation of depressive and anxiety symptoms by using data on personality traits in a longitudinal, genetically-informative design. The findings suggested the personality traits from Gray's RST model played an important role in the prediction, and clarified the description, of both depressive and anxiety symptoms.

A Brief History of the Collaboration between Dr Nathan Gillespie and Professor Nick Martin Including Personal Reflections

This article describes Dr Nathan Gillespie's PhD training and supervision under Professor Nick Martin and their ongoing collaborations. Drs Gillespie and Martin have collaborated on numerous biometrical genetic analyses applied to cross-sectional and longitudinal twin data, combined molecular and phenotypic modeling, as well as genomewide meta-analyses of psychoactive substance use and misuse. Dr Gillespie remains an active collaborator with Professor Martin, including ongoing data collection, analysis and publications related to the Brisbane Longitudinal Twin Study.

Assessing causal pathways between physical formidability and aggression in human males

Studies suggest the existence of an association between the physical formidability of human males and their level of aggression. This association is theoretically predictable from animal models of conflict behavior but could emerge from multiple different causal pathways. Previous studies have not been able to tease apart these paths, as they have almost exclusively relied on bivariate correlations and cross-sectional data. Here, we apply longitudinal twin data from two different samples to (1) estimate the direction of causality between formidability and aggression by means of quasi-experimental methods and (2) estimate the relative contribution of genetic and environmental factors by means of twin modeling. Importantly, the results suggest, on the one hand, that the association between formidability and aggression is less reliable than previously thought. On the other hand, the results also suggest that when the association occurs, the causal direction is from formidability to aggression and the primary part of the causal relationship is genetic in nature. These latter findings are consistent with adaptionist models suggesting that human male aggression is ‘reactively heritable’ to genetic components of formidability.

Genetic influences on alcohol use behaviors have diverging developmental trajectories: a prospective study among male and female twins.

Both alcohol-specific genetic factors and genetic factors related to externalizing behavior influence problematic alcohol use. Little is known, however, about the etiologic role of these 2 components of genetic risk on alcohol-related behaviors across development. Prior studies conducted in a male cohort of twins suggest that externalizing genetic factors are important for predicting heavy alcohol use in adolescence, whereas alcohol-specific genetic factors increase in importance during the transition to adulthood. In this report, we studied twin brothers and sisters and brother-sister twin pairs to examine such developmental trajectories and investigate whether sex and cotwin sex effects modify these genetic influences. We used prospective, longitudinal twin data collected between ages 12 and 22 within the population-based FinnTwin12 cohort study (analytic n=1,864). Our dependent measures of alcohol use behaviors included alcohol initiation (age 12), intoxication frequency (ages 14 and 17), and alcohol dependence criteria (age 22). Each individual's genetic risk of alcohol use disorders (AUD-GR) was indexed by his/her parents' and cotwin's DSM-IV Alcohol Dependence (AD) criterion counts. Likewise, each individual's genetic risk of externalizing disorders (EXT-GR) was indexed with a composite measure of parents' and cotwin's DSM-IV Conduct Disorder and Antisocial Personality Disorder criterion counts. EXT-GR was most strongly related to alcohol use behaviors during adolescence, while AUD-GR was most strongly related to alcohol problems in young adulthood. Further, sex of the twin and sex of the cotwin significantly moderated the associations between genetic risk and alcohol use behaviors across development: AUD-GR influenced early adolescent alcohol use behaviors in females more than in males, and EXT-GR influenced age 22 AD more in males than in females. In addition, the associations of AUD-GR and EXT-GR with intoxication frequency were greater among 14- and 17-year-old females with twin brothers. We found divergent developmental trajectories for alcohol-specific and externalizing behavior-related genetic influences on alcohol use behaviors; in early adolescence, genetic influences on alcohol use behaviors are largely nonspecific, and later in adolescence and young adulthood, alcohol-specific genetic influences on alcohol use are more influential. Importantly, within these overall trajectories, several interesting sex differences emerged. We found that the relationship between genetic risk and problematic drinking across development is moderated by the individual's sex and his/her cotwin's sex. AUD-GR influenced adolescent alcohol outcomes in females more than in males and by age 22, EXT-GR influenced AD criteria more for males than females. In addition, the association between genetic risk and intoxication frequency was greater among 14- and 17-year-old females with male cotwins.

Genetic and environmental stability of intelligence in childhood and adolescence.

The present study examined the genetic and environmental contributions to the temporal stability of verbal, non-verbal and general intelligence across a developmental period spanning childhood and adolescence (5-18 years). Longitudinal twin data collected in four different studies on a total of 1,748 twins, comprising 4,641 measurement points in total, were analyzed using genetic adaptations of the simplex model. The heterogeneity in the type of instrument used to assess psychometric intelligence across the different subsamples and ages allowed us to address the auxiliary question of how to optimally utilize the existing longitudinal data in the context of gene-finding studies. The results were consistent across domains (verbal, non-verbal and general intelligence), and indicated that phenotypic stability was driven primarily by the high stability of additive genetic factors, that the stability of common environment was moderate, and that the unique environment contributed primarily to change. The cross-subscale stability was consistently low, indicating a small overlap between different domains of intelligence over time. The high stability of additive genetic factors justifies the use of a linear combination of scores across the different ages in the context of gene-finding studies.

GE covariance through phenotype to environment transmission: an assessment in longitudinal twin data and application to childhood anxiety.

We considered identification of phenotype (at occasion t) to environment (at occasion t + 1) transmission in longitudinal model comprising genetic, common and unique environmental simplex models (autoregressions). This type of transmission, which gives rise to genotype-environment covariance, is considered to be important in developmental psychology. Having established identifying constraints, we addressed the issue of statistical power to detect such transmission given a limited set of parameter values. The power is very poor in the ACE simplex, but is good in the AE model. We investigated misspecification, and found that fitting the standard ACE simplex to covariance matrices generated by an AE simplex with phenotype to E transmission produces the particular result of a rank 1 C (common environment) covariance matrix with positive transmission, and a rank 1 D (dominance) matrix given negative transmission. We applied the models to mother ratings of anxiety in female twins (aged 3, 7, 10, and 12 years), and obtained support for the positive effect of one twin’s phenotype on the other twin’s environment.

Inference about Causation from Examination of Familial Confounding: Application to Longitudinal Twin Data on Mammographic Density Measures that Predict Breast Cancer Risk

Mammographic density is a strong risk factor for breast cancer. It is unknown whether there are different causes of variation in mammographic density at different ages. Mammograms and questionnaires were obtained on average 8 years apart from 327 Australian female twin pairs (204 monozygous and 123 dizygous). Mammographic dense area and percentage dense area were measured using a computer-assisted method. The correlational structure of the longitudinal twin data was estimated under a multivariate normal model using FISHER. Inference about causation from examination of familial confounding was made by regressing each twin's recent mammographic density measure against one or both of her and her co-twin's past measures. For square root dense area and percentage dense area (age- and body mass index-adjusted), the correlations over time within twins were 0.86 and 0.82, and the cross-twin correlations were 0.71 and 0.65 for monozygous pairs and 0.25 and 0.20 for dizygous pairs, respectively. As a predictor of a twin's recent dense area, the regression coefficient (SE) for the co-twin's past dense area reduced after adjusting for her own past measure from 0.84 (0.03) to 0.09 (0.03) for monozygous pairs and from 0.63 (0.04) to 0.04 (0.03) for dizygous pairs. Corresponding estimates for percentage dense area were 0.73 (0.04), 0.10 (0.03), 0.42 (0.05), and 0.03 (0.03). Mammographic density measures are highly correlated over time and the familial/genetic components of their variation are established before mid-life. Mammographic density of young women could provide a means for breast cancer control.

A Biometric Latent Curve Analysis of Memory Decline in Older Men of the NAS-NRC Twin Registry

Previous research has shown cognitive abilities to have different biometric patterns of age-changes. We examined the variation in episodic memory (word recall task) for over 6,000 twin pairs who were initially aged 59-75, and were subsequently re-assessed up to three more times over 12 years. In cross-sectional analyses, variation in the number of words recalled independent of age was explained largely by non-shared influences (65-72%), with clear additive genetic influences (12-32%), and marginal shared family influences (1-18%). The longitudinal phenotypic analysis of the word recall task showed systematic linear declines over age, but several nonlinear models with more dramatic changes at later ages, improved the overall fit. A two-part spline model for the longitudinal twin data with an optimal turning point at age 74 led to: (a) a separation of non-shared environmental influences and transient measurement error (~50%); (b) strong additive genetic components of this latent curve (~44% at age 60) with increases (over 50%) up to age 74, but with no additional genetic variation after age 74; (c) the smaller influences of shared family environment (~15% at age 74) were constant over all ages; (d) non-shared effects play an important role over most of the life-span but diminish after age 74.

Direction of Causation Between Shared and Non-Shared Environmental Factors

Determining the direction of causation between two related variables is an interesting and challenging problem. A simple regression model is a frequently used statistical tool to find out whether a dependent variable is significantly predicted by an independent variable; however using a simple regression model cannot determine the direction of causation, because the model fit takes no account of this direction. As an approach to this problem, non-normal structural equation modeling (nnSEM; Shimizu and Kano, J Stat Plan Inference 138:3483-3491, 2008) using higher order moments (third, fourth,...) as well as first and second order moments, can be useful. This method enables us to determine the direction of causation using goodness of fit, even for a simple regression model. In this paper, nnSEM is applied to behavior genetics, in particular, to the genetic simplex model. In this context, nnSEM enables us to determine the direction of causation between C (shared environment) factors and between E (non-shared environment) factors. The efficiency of this method is illustrated by simulation studies and the analysis of real longitudinal twin data.

Genetic variance in processing speed drives variation in aging of spatial and memory abilities.

Previous analyses have identified a genetic contribution to the correlation between declines with age in processing speed and higher cognitive abilities. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories for processing speed and cognitive abilities. Longitudinal twin data from the Swedish Adoption/Twin Study of Aging, including up to 5 measurement occasions covering a 16-year period, were available from 806 participants ranging in age from 50 to 88 years at the 1st measurement wave. Factors were generated to tap 4 cognitive domains: verbal ability, spatial ability, memory, and processing speed. Model-fitting indicated that genetic variance for processing speed was a leading indicator of variation in age changes for spatial and memory ability, providing additional support for processing speed theories of cognitive aging.

Mapping growth patterns and genetic influences on early brain development in twins.

Despite substantial progress in understanding the anatomical and functional development of the human brain, little is known on the spatial-temporal patterns and genetic influences on white matter maturation in twins. Neuroimaging data acquired from longitudinal twin studies provide a unique platform for scientists to investigate such issues. However, the interpretation of neuroimaging data from longitudinal twin studies is hindered by the lacking of appropriate image processing and statistical tools. In this study, we developed a statistical framework for analyzing longitudinal twin neuroimaging data, which is consisted of generalized estimating equation (GEE2) and a test procedure. The GEE2 method can jointly model imaging measures with genetic effect, environmental effect, and behavioral and clinical variables. The score test statistic is used to test linear hypothesis such as the association between brain structure and function with the covariates of interest. A resampling method is used to control the family-wise error rate to adjust for multiple comparisons. With diffusion tensor imaging (DTI), we demonstrate the application of our statistical methods in quantifying the spatiotemporal white matter maturation patterns and in detecting the genetic effects in a longitudinal neonatal twin study. The proposed approach can be easily applied to longitudinal twin data with multiple outcomes and accommodate incomplete and unbalanced data, i.e., subjects with different number of measurements.

Attributional style as a risk marker of genetic effects for adolescent depressive symptoms.

Genetic effects on adolescent depression have been consistently reported, but little is known about mediating pathways from the distal genotype to resultant behavioral symptoms. Identifying intermediate risk markers may provide clues on these pathways. In the present study, longitudinal twin and sibling data were used to address 3 issues pertaining to attributional style as a putative marker of genetic risk for adolescent depression: state independence by assessing predictive effects between attributional style and depressive symptoms, heritability of attributional style at different time points, and genetic links between attributional style and depressive symptoms characterizing concurrent and longitudinal associations. The authors further examined whether these predictive and genetic links varied across levels of stress, age, and gender. Negative attributions preceded, co-occurred with, and followed symptoms. The predictive association between earlier negative attributions and later depressive symptoms did not differ by stress, age, or gender. Attributional style was moderately heritable at both time points. Genetic links with concurrent and prospective depressive symptoms were larger in individuals reporting higher levels of stress, who were older and female. Implications for attributional style as a marker reflecting genetic risks are discussed.

Word reading and reading comprehension: stability, overlap and independence

Longitudinal twin data were analyzed to investigate the etiology of the stability of genetic and environmental influences on word reading and reading comprehension, as well as the stability of those influences on their relationship. Participating twin pairs were initially tested at a mean age of 10.3 years, and retested approximately five years later. Both word reading and comprehension were found to be highly stable, and genetic influences were primarily responsible for that stability. In contrast to studies with younger participants, no unique genetic influences were observed at follow-up testing in this older sample. High genetic correlations were obtained between word reading and reading comprehension at both ages, indicating common genetic influences. However, significant genetic influence on comprehension was also observed, independent of that on word reading. Although the phenotypic relation between the two measures appeared to decline across time, the genetic etiology of this relation was highly stable.

A Longitudinal Genetic Study of Plasma Lipids in Adolescent Twins

Plasma lipids such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol and triglyceride levels contribute to variation in the risk of cardiovascular disease. The early stages of atherosclerosis in childhood have also been associated with changes in triglycerides, LDL and HDL. Heritability estimates for lipids and lipoproteins for adolescents are in the range .71 to .82, but little is known about changes of genetic and environmental influences over time in adolescence. We have investigated the contribution of genetic and environmental influences to variation in lipids in adolescent twins and their nontwin siblings using longitudinal twin and family data. Plasma HDL and LDL cholesterol, total cholesterol and triglycerides data from 965 twin pairs at 12, 14 and 16 years of age and their siblings have been analyzed. Longitudinal genetic models that included effects of age, sex and their interaction were fitted to assess whether the same or different genes influence each trait at different ages. Results suggested that more than one genetic factor influences HDL, LDL, total cholesterol and triglycerides over time at ages 12, 14 and 16 years. There was no evidence of shared environmental effects except for HDL and little evidence of long-term nonshared environmental effects was found. Our study suggested that there are developmental changes in the genes affecting plasma lipid concentrations across adolescence.

Longitudinal Genetic Analysis of Plasma Lipids

The consensus from published studies is that plasma lipids are each influenced by genetic factors, and that this contributes to genetic variation in risk of cardiovascular disease. Heritability estimates for lipids and lipoproteins are in the range .48 to .87, when measured once per study participant. However, this ignores the confounding effects of biological variation measurement error and ageing, and a truer assessment of genetic effects on cardiovascular risk may be obtained from analysis of longitudinal twin or family data. We have analyzed information on plasma high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides, from 415 adult twins who provided blood on two to five occasions over 10 to 17 years. Multivariate modeling of genetic and environmental contributions to variation within and across occasions was used to assess the extent to which genetic and environmental factors have long-term effects on plasma lipids. Results indicated that more than one genetic factor influenced HDL and LDL components of cholesterol, and triglycerides over time in all studies. Nonshared environmental factors did not have significant long-term effects except for HDL. We conclude that when heritability of lipid risk factors is estimated on only one occasion, the existence of biological variation and measurement errors leads to underestimation of the importance of genetic factors as a cause of variation in long-term risk within the population. In addition our data suggest that different genes may affect the risk profile at different ages.