Non-additive and Additive Genetic Effects on Extraversion in 3314 Dutch Adolescent Twins and Their Parents

The influence of non-additive genetic influences on personality traits has been increasingly reported in adult populations. Less is known, however, with respect to younger samples. In this study, we examine additive and non-additive genetic contributions to the personality trait of extraversion in 1,689 Dutch twin pairs, 1,505 mothers and 1,637 fathers of the twins. The twins were on average 15.5 years (range 12-18 years). To increase statistical power to detect non-additive genetic influences, data on extraversion were also collected in parents and simultaneously analyzed. Genetic modeling procedures incorporating age as a potential modifier of heritability showed significant influences of additive (20-23%) and non-additive genetic factors (31-33%) in addition to unshared environment (46-48%) for adolescents and for their parents. The additive genetic component was slightly and positively related to age. No significant sex differences were found for either extraversion means or for the magnitude of the genetic and environmental influences. There was no evidence of non-random mating for extraversion in the parental generation. Results show that in addition to additive genetic influences, extraversion in adolescents is influenced by non-additive genetic factors.     

An evolutionary perspective on the trans-generational basis of obesity

Until recently, obesity was considered the product of interactions between genotype and lifestyle. However, recent work suggests that the genetic heritability of adiposity has been over-estimated, whilst epidemiological studies show that although many genes are associated with nutritional status, the effect of each is very small. A polygenic basis of obesity risk may arise through bet-hedging of numerous traits to accommodate diverse unpredictable environments, rather than through systematic local adaptation. Such 'fragmentation' of the genetic component of metabolism across multiple alleles may be a necessary pre-requisite for complementary enhancement of phenotypic plasticity. The inter-generational component of obesity refers to phenotypic effects transmitted across generations, arising from exposure to maternal, familial and environmental niches during development. Inter-generational transfers of somatic capital (height, lean mass) may respond to ecological conditions through a slow-response damping system, through the influence of maternal phenotype on offspring growth and body composition. The primary traits subject to inter-generational effects may be physique and life history strategy, with adiposity both aiding and responding as a flexible risk management strategy. The biological processes that underpin the offspring's developmental plasticity appear sensitive to the obesogenic niche. Through this sensitivity, diverse environmental factors can induce excess weight gain from childhood onwards.     

Maternal and paternal effects on offspring internalizing problems: Results from genetic and family‐based analyses

It is unclear to what extent parental influences on the development of internalizing problems in offspring are explained by indirect genetic effects, reflected in the environment provided by the parent, in addition to the genes transmitted from parent to child. In this study, these effects were investigated using two innovative methods in a large birth cohort. Using maternal‐effects genome complex trait analysis (M‐GCTA), the effects of offspring genotype, maternal or paternal genotypes, and their covariance on offspring internalizing problems were estimated in 3,801 mother–father–child genotyped trios. Next, estimated genetic correlations within pedigree data, including 10,688 children, were used to estimate additive genetic effects, maternal and paternal genetic effects, and a shared family effect using linear mixed effects modeling. There were no significant maternal or paternal genetic effects on offspring anxiety or depressive symptoms at age 8, beyond the effects transmitted via the genetic pathway between parents and children. However, indirect maternal genetic effects explained a small, but nonsignificant, proportion of variance in childhood depressive symptoms in both the M‐GCTA (~4%) and pedigree (~8%) analyses. Our results suggest that parental effects on offspring internalizing problems are predominantly due to transmitted genetic variants, rather than the indirect effect of parental genes via the environment.     

Co-occurrence of Aggressive Behavior and Rule-Breaking Behavior at Age 12: Multi-Rater Analyses

Aggressive Behavior (AGG) and Rule-Breaking Behavior (RB) are two of the eight CBCL syndromes. The phenotypic correlation between AGG and RB ranges from .48 to .76, and varies depending on the rater and the sex of the child. Prevalence of AGG and RB (i.e., T 67) is in the range of 6%–7% in both boys and girls. Fifty percent to 60% of the children who are deviant on AGG are also deviant on RB and vice versa. Why so many children show problem behavior in the clinical range for both syndromes is unclear. This co-occurrence could be due to genetic factors influencing both traits, to environmental factors influencing both traits, or to both. The purpose of this study is to use a genetically informative sample to estimate genetic and environmental influences on AGG and RB and to investigate the etiology of the co-occurrence of both behaviors. We do this using multiple informants to take into account underlying sources of parental agreement and disagreement in ratings of their offspring. To this end, mother and father ratings of AGG and RB were collected by using the Child Behavior Checklist in a large sample of 12-year-old twins. Parental agreement is represented by an interparent correlation in the range of .53–.76, depending on phenotype (AGG or RB) and sex of the child. Genetic influences account for 79% and 69% of the individual differences in RB and AGG behavior (defined as AGG and RB on which both parents do agree) in boys. In girls 56% and 72% of the variance in RB and AGG are accounted for by genetic factors. Shared environmental influences are significant for RB in girls only, explaining 23% of the total variance. Eighty percent of the covariance between AGG and RB, similarly assessed by both parents, can be explained by genetic influences. So, co-occurrence in AGG and RB is mainly caused by a common set of genes. Parental disagreement seems to be a combination of so-called rater bias and of parental specific views.     

Estimating genetic correlations among discontinuous phenotypes: An analysis of criminal convictions and psychiatric-hospital diagnoses in Danish adoptees

A biometrical model-fitting approach was applied to data from a full adoption design to study phenotypic variation and covariation among multiple discontinuous traits. Using statistical methods available for factor analyses of dichotomous-item data, generalized least-squares estimates were obtained for parameters of additive polygenic and environmental influences on criminal convictions and psychiatric-hospital diagnoses in 2532 Danish male adoptees and their family members. The procedure also provided estimates of genetic correlations, environmental correlations, and genotype-environment correlations among the measures while taking into account the effects of selective placement, assortative mating, and cultural transmission from parental phenotypes to off-spring environments. Significant heritable influences were found for property crime and for a composite psychiatric variable pertaining to hospital admissions for alcohol abuse, drug abuse, and personality disorders. Both correlated environmental factors and correlated genetic factors important to the different variables accounted for the observed phenotypic relationship between property crime and these antisocial disorders. No cultural transmission was present for the adoptees' antisocial disorders, although significant paternal cultural transmission was found for property crimes. Patterns of assortative mating differed for the biological versus adoptive parents, and selective placement was found to be negligible.This work was supported by NIMH Grant MH39904-01 and PHS Grant 31353 from the Center for Studies of Crime and Delinquency.     

Discriminating among single locus models using small pedigrees

Simulated small pedigrees (2 parents, 4 offspring) were used to illustrate the applications and limitations of a “model choice” approach designed to detect genetic heterogeneity in familial diseases. While it is possible to identify groups of pedigrees which have different genetic causes for quantitative phenotypic trait(s), theoretical limitations on discriminating between 4 single locus models exist for certain pedigree structures. These limitations originate from the overlapping phenotypic predictions of the various genetic models. Such limitations must be carefully considered in the design of genetic studies. Studies aimed at detecting genetic heterogeneity in familial diseases should limit the different genetic models being considered and tailor the sampling strategy to avoid collecting pedigrees which are non-informative for certain comparisons.     

The genetic epidemiology of parental discipline

BACKGROUND: Previous studies of parental discipline have identified little influence of heritability on parental control, and some influence of gene-environment correlations, shared environment and child temperament. METHOD: Using interview data from 2003 female twins from a population-based twin registry and 1472 of their parents, we examined reports of parental discipline from four perspectives: (1) father and mother reporting separately on the type of discipline they provided for their offspring; (2) each twin reporting on the type of discipline they received from their parents; (3) each parent reporting on the discipline provided by their spouse; and, (4) each twin reporting on the discipline they provided for their own offspring. Using factor analysis and univariate structural equation modelling, we examined the structure of parental discipline, and the genetic and environmental influences thereon. RESULTS: The seven discipline items yielded two factors, physical discipline and limit setting, which were moderately positively correlated. Parents perceived discipline as largely a common environmental experience for the twins, whereas the twins indicated that discipline was influenced by unique environmental factors and the genotype of the child. Twins as parents indicated no influence of shared environment on discipline, with the majority of influence accounted for by non-shared environment and parental genotype. CONCLUSIONS: Parents recall providing similar discipline to their children, whereas children emphasize the differences in parental discipline. Sources of individual variation in parental discipline vary according to which family member report is examined. In total, parental discipline is partially influenced by the genotype of both the parent and child, and by environmental factors shared by the twins and unique to the individual.     

Quantitative genetic analysis of IQ development in young children: Multivariate multiple regression with orthogonal polynomials

The study of psychological development has recently benefited from innovative analytic methods for estimating and examining the correlates of individual growth curves. These methods are more consistent with a conceptualization of development as an ongoing, continuous process, rather than as increases or decreases in a trait between two discrete time points. Recent developmental behavior genetic models have focused on continuity and change in the genetic and environmental influences underlying phenotypes. In contrast, we present a model for genetic and environmental influences on phenotypic development per se. In this model, we adapted multiple regression methods developed for twin designs (DeFries and Fulker, 1985) to a parent-offspring adoption design and to a multivariate framework in which repeated measurements are decomposed into orthogonal polynomial trends. We applied these analyses to the development of IQ during infancy and early childhood using parent-offspring data from adoptive and nonadoptive families in the Colorado Adoption Project. The results suggested familial environmental influences on children's mean IQ for ages 1–4 but environmental influences specific to fathers' cognitive ability on children's IQ development. We also discuss advantages and disadvantages of the multivariate multiple regression method for studying genetic and environmental influences on development.     

Ontogeny in the Family

When ontogeny takes place in a family, and parents provide essential resources for development, the parents become an environmental component to the development of a wide range of offspring traits. Because differences among parents may partly reflect genetic variation, this environmental component contains genes and may itself evolve. Also, when offspring play an active role in family interactions, offspring become a social environmental component to parents, affecting their behavior in turn, which potentially results in reciprocal social selection. Thus, an evolutionary process of coadaptation to family life, additionally driven by conflicts of interests, may have shaped the expression and development patterns underlying infant behaviors. The complex genetics arising from family interactions can be formalized by extending standard quantitative genetic models. These models demonstrate how the explicit consideration of the family environment can profoundly alter both the expression and evolutionary response to selection of behaviors involved in family interactions. Behavioral genetic studies have begun to unravel the complex genetics underlying infant solicitation behaviors and parental provisioning, although many focus on one side of the interaction. A genetic analysis incorporating interactions among family members explicitly may be critical because the genes underlying the expression of parental provisioning indirectly affect offspring behaviors, and vice versa.     

Analysis of behavioral traits in the presence of cultural transmission and assortative mating: Applications to IQ and SES

General linear models of familial resemblance are described which allow for polygenic inheritance, cultural transmission from parent to offspring, phenotypic assortative mating, common environment, and maternal and parental effects. These models use observed phenotypic correlations between multiple classes of relatives and/or correlations between individuals reared in separated and extended family structures to yield maximum likelihood parameter estimates. The models are first applied to American kinship data for IQ, with the variance of IQ partitioned as 30% additive genetic, 29% due to cultural inheritance, 9% due to gene-culture covariance, and 32% due to nontransmissible environment. Under the assumption that the correlations between (nontransmissible) environments of DZ and MZ twins are the same, an approximate treatment of dominance yields an estimate of 23% dominance variation.This work was supported in part by USPHS Grants AA-03539, MH-07081, MH-25430, and MH-31302 and by Research Scientist Development Award MH-00048 (C. R. C.).     

The intergenerational transmission of externalizing behaviors in adult participants: the mediating role of childhood abuse

Childhood abuse was investigated as a potential mediator of the intergenerational transmission of externalizing behaviors (EXT) in adulthood among a large general population sample drawn from the National Comorbidity Survey. Community participants (N = 5,424) underwent diagnostic and psychosocial interviews and reported on their own adult symptoms of antisocial behavior and substance dependence, parental symptoms, and childhood abuse history. Multiple group structural equation modeling revealed that (a) EXT in parents was associated with childhood abuse in offspring, particularly among mother- daughter dyads, (b) abuse had a unique influence on adult EXT in offspring above parental EXT, and (c) abuse accounted for the relationship between parental EXT and offspring EXT in female but not male participants. This article emphasizes the importance of examining different environmental processes which may explain familial transmission of destructive behaviors in men and women and highlights the importance of family interventions that target parental symptoms to ameliorate risk to offspring.     

Heritability Estimation for Speech-Sound Traits with Developmental Trajectories

Numerous studies have examined genetic influences on developmental problems such as speech sound disorders (SSD), language impairment (LI), and reading disability. Disorders such as SSD are often analyzed using their component endophenotypes. Most studies, however, have involved comparisons of twin pairs or siblings of similar age, or have adjusted for age ignoring effects that are peculiar to age-related trajectories for phenotypic change. Such developmental changes in these skills have limited the usefulness of data from parents or siblings who differ substantially in age from the probands. Employing parent–offspring correlation in heritability estimation permits a more precise estimate of the additive component of genetic variance, but different generations have to be measured for the same trait. We report on a smoothing procedure which fits a series of lines that approximate a curve matching the developmental trajectory. This procedure adjusts for changes in measures with age, so that the adjusted values are on a similar scale for children, adolescents, and adults. We apply this method to four measures of phonological memory and articulation in order to estimate their heritability. Repetition of multisyllabic real words (MSW) showed the best heritability estimate of 45% in this sample. We conclude that differences in measurement scales across the age span can be reconciled through non-linear modeling of the developmental process.     

Parental Education and Child's Verbal IQ in Adoptive and Biological Families in the National Longitudinal Study of Adolescent Health

This study compared adoptive children and matched, biological children to estimate the genetic and environmental effect of years of mothers' and fathers' education on children's verbal intelligence (VIQ), as assessed by knowledge of vocabulary words. Adoptive and biological adolescent children in the National Longitudinal Study of Adolescent Health (Add Health) were matched for sex, age, parental education, and ethnicity. The adolescents all resided with two parents. Structural equation modeling was employed using Mx to estimate the genetic and transmissible environmental components of the correlation between parental education and children's VIQ. The mother-child and father-child correlations in biological families were .41 and .36, respectively, vs .16 and .18 in adoptive families. As suggested by these correlations, both genetic and shared environmental influences were statistically significant in the Mx models. We conclude that parental education exerts a modest shared environmental effect, explaining no more than 3 to 4% of the variation in verbal intelligence.     

The resolution of cultural and biological inheritance: Informativeness of different relationships

The informativeness of different relationships for resolving the genetic and cultural transmission of a continuous variable is explored by computer simulation. Extended twin, extended nuclear-family, and adoption designs are considered. Combining data on twin and parent-offspring pairs provides a powerful means of detecting genetic and cultural transmission. The addition of uncle-nephew and first-cousin data sometimes leads to an increase in power. Designs involving monozygotic twin pairs and their offspring are weaker. The most powerful adoption designs involve data on both biological parent-adopted-away offspring and adoptive parent-adopted offspring pairs. In the absence of information about biological parents, combining nuclear-family, adoptive parent-adopted offspring, and adoptive/natural sibling relationships still provides a powerful strategy for hypothesis testing. Adoption designs are more robust than extended twin and extended nuclear-family designs for resolving cultural and biological inheritance in the presence of genetic dominance or phenotypic assortative mating.Research reported in this paper was supported by Grants GM30250, GM32732, and AG04954 from the National Institutes of Health and by the Department of Mental Health and Mental Retardation of the Commonwealth of Virginia.     

Exploring the inter-relationship of smoking age-at-onset, cigarette consumption and smoking persistence: genes or environment?

BACKGROUND: We investigated the genetic and environmental contributions to covariation between smoking age-at-onset, cigarette consumption and smoking persistence. METHOD: Multivariate biometrical modelling methods were applied to questionnaire data from Australian twins and their siblings (14 472 individuals from 6247 families). The contributions of genetic and environmental factors to covariation between the three traits were estimated, allowing for sex differences in both trait prevalence and the magnitude of genetic and environmental effects. RESULTS: All traits were moderately heritable in males and females (estimates between 0.40 and 0.62), but there were sex differences in the extent to which additive genetic influences were shared across traits. Twin-specific environmental factors accounted for a substantial proportion of the variance in smoking age-at-onset in females (0.19) and males (0.12), but had little influence (<0.08) on other traits. Unique environmental factors were estimated to have a moderate influence on smoking age-at-onset (0.17 for females, 0.19 for males), but a stronger influence on other traits (between 0.39 and 0.49). CONCLUSIONS: These results provide some insight into observed sex differences in smoking behaviour, and suggest that searching for pleiotropic genes may prove fruitful. However, further work on phenotypic definitions of smoking behaviour, particularly persistence, is warranted.     

Major gene and multifactorial inheritance of mandibular prognathism

Mandibular prognathism typically shows familial aggregation. Various genetic models have been described and it is assumed to be a multifactorial and polygenic trait, with a threshold for expression. Our goal was to examine specific genetic models of the familial transmission of this trait. The study sample comprised of 2,562 individuals from 55 families. Complete family histories for each proband were ascertained and the affection status of relatives were confirmed by lateral cephalograms, photographs, and dental models. Pedigrees were drawn using PELICAN and complex segregation analysis was performed using POINTER. Parts of some pedigrees were excluded to create one founder pedigrees, so the total N was 2,050. Analysis showed more affected females than males (P = 0.030). The majority of the pedigrees suggest autosomal dominant inheritance. Incomplete penetrance was demonstrated by the ratio of affected/unaffected parents and siblings. The heritability of mandibular prognathism was estimated to be 0.316. We conclude that there is a major gene that influences the expression of mandibular prognathism with clear signs of Mendelian inheritance and a multifactorial component.     

Mendelian inheritance of polygenic diseases: a hypothetical basis for increasing incidence

The incidence of common polygenic diseases, such as type 1 diabetes, bronchial asthma, and gluten-sensitive enteropathy, is increasing. Although this is usually attributed to environmental factors, it is possible that this rising incidence also has a genetic basis. The hypothesis is put forth that, in the past, these diseases, with their increased morbidity and mortality, were selected against. In contrast to monogenic diseases, the incidence of polygenic diseases can be reduced by selection against susceptibility alleles of any of the genetic loci necessary for disease to occur. In different isolated populations, different disease susceptibility loci may have been selected against. Parents who derive from different isolated populations in which there are inversely different susceptibility allele frequencies because of selection or genetic drift, would be expected to have offspring with an increased risk for that polygenic disease. It is shown mathematically that the incidence of a hypothetical polygenic disease increases under these circumstances. The increased risk in these offspring results from a kind of genetic complementation in which they have inherited a more complete set of susceptibility alleles at all susceptibility loci than is carried by either of their parents. Hallmarks of this hypothesized phenomenon would be increased heterozygosity for specific population markers (whether susceptibility alleles or not) among the disease-affected offspring and a paucity of such heterozygotes among their parents. The parents and patients would also be expected to give more evidence of ethnic or subethnic disparity than that observed in controls.     

Bivariate path analysis of familial resemblance for reading ability and symbol processing speed

A bivariate path model which incorporates measures of phenotypic assortative and cross-assortative mating is formulated for the analysis of familial resemblance for two characters in nuclear families (parents and at least one child). The model facilitates the partitioning of phenotypic variances for the two characters and their covariance into components due to transmissible familial (genetic and/or family environmental) influences and specific, nontransmissible environmental influences. The model is applied to the joint transmission of reading ability and symbol processing speed in families with a reading-disabled child and in those with children of normal reading ability. Although the model is not adequate to explain data on families with a reading-disabled child, it provides an acceptable fit to the data on control families, and parameter estimates obtained for the two data sets are very similar. Familial sources of variation are important for both reading ability and symbol processing speed, and more than half of the phenotypic correlation between the two variables is due to familial influences.This work was supported in part by grants from the Spencer Foundation and NICHD (HD-11681) to J. C. DeFries.     

Genetic and Environmental Sources of Individual Religiousness: The Roles of Individual Personality Traits and Perceived Environmental Religiousness

In the current study, we examined the genetic and environmental sources of the links between individual religiousness and individual personality traits, perceived parental religiousness, and perceived peer religiousness. Data from 870 individuals (incl. 394 twin pairs) were analyzed. Variance in individual religiousness was significantly influenced by genetic effects, environmental influences shared by twins reared together, and individual-specific environmental influences. Individual religiousness showed significant associations with age, sex, specific personality traits (e.g., agreeableness, openness to values), and perceived religiousness of important social interaction partners, such as parents, best friends, and spouses. The links to personality traits were relatively small and primarily genetically mediated. The associations between individual religiousness and parental religiousness were substantial and mediated by shared environmental effects. These links significantly decreased across age accompanying a significant decrease of shared environmental influences on individual religiousness. The correlations between individual religiousness and perceived religiousness of spouses and best friends were relatively moderate but increased with age. These associations were mediated by genetic as well as nonshared environmental sources accompanying an increase of nonshared environmental influences on individual religiousness with age. The results suggest that inter-individual differences in religiousness are due to multiple sources.     

Current parental depression and offspring perceived self-competence: a quasi-experimental examination

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52?%) and female offspring aged 15.7?±?2.4?years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression.