Bridging temperament and the Big Five in children: A genetically informative study.

Early temperament precedes children's emerging Big Five personality, but shared models of temperament and personality are scarce. We wanted to estimate the genetic factor structure underlying both temperament and the Big Five in children, employing a genetically informed study. Within the Norwegian Mother and Child Cohort Study, we selected 26,354 twins, siblings, and cousins. Mothers rated their children's temperament three times between the ages of 1.5 and 5 years, and the children's Big Five personality at the age of 8. We analyzed the data using biometric modeling. The mean heritability of single-time temperamental traits and Big Five personality traits was .48 and .45, respectively. The mean genetic correlations of temperament across time were .80. The genetic correlations of temperament at 5 years and the Big Five at 8 years revealed two factors, the first comprising reversed Big Five Neuroticism, Agreeableness, Conscientiousness, and reversed EAS Emotionality, the second comprising Big Five Extraversion, Openness to Experience, EAS Activity, Sociability, and reversed Shyness. A confirmatory factor analysis estimated the two factors showing heritabilities of .96 and .72, respectively. The two factors mirrored the metatraits Stability and Plasticity by John M. Digman. Temperament and personality in childhood can be meaningfully bridged using just two metafactors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genetic similarity between relatives provides evidence on the presence and history of assortative mating.

Assortative mating - the non-random mating of individuals with similar traits - is known to increase trait-specific genetic variance and genetic similarity between relatives. However, empirical evidence is limited for many traits, and the implications hinge on whether assortative mating has started recently or many generations ago. Here we show theoretically and empirically that genetic similarity between relatives can provide evidence on the presence and history of assortative mating. First, we employed path analysis to understand how assortative mating affects genetic similarity between family members across generations, finding that similarity between distant relatives is more affected than close relatives. Next, we correlated polygenic indices of 47,135 co-parents from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and found genetic evidence of assortative mating in nine out of sixteen examined traits. The same traits showed elevated similarity between relatives, especially distant relatives. Six of the nine traits, including educational attainment, showed greater genetic variance among offspring, which is inconsistent with stable assortative mating over many generations. These results suggest an ongoing increase in familial similarity for these traits. The implications of this research extend to genetic methodology and the understanding of social and economic disparities.

Intergenerational transmission of ADHD behaviors: genetic and environmental pathways.

BACKGROUND: We investigate if covariation between parental and child attention-deficit hyperactivity disorder (ADHD) behaviors can be explained by environmental and/or genetic transmission. METHODS: We employed a large children-of-twins-and-siblings sample (N = 22 276 parents and 11 566 8-year-old children) of the Norwegian Mother, Father and Child Cohort Study. This enabled us to disentangle intergenerational influences via parental genes and parental behaviors (i.e. genetic and environmental transmission, respectively). Fathers reported on their own symptoms and mothers on their own and their child's symptoms. RESULTS: Child ADHD behaviors correlated with their mother's (0.24) and father's (0.10) ADHD behaviors. These correlations were largely due to additive genetic transmission. Variation in children's ADHD behaviors was explained by genetic factors active in both generations (11%) and genetic factors specific to the children (46%), giving a total heritability of 57%. There were small effects of parental ADHD behaviors (2% environmental transmission) and gene-environment correlation (3%). The remaining variability in ADHD behaviors was due to individual-specific environmental factors. CONCLUSIONS: The intergenerational resemblance of ADHD behaviors is primarily due to genetic transmission, with little evidence for parental ADHD behaviors causing children's ADHD behaviors. This contradicts theories proposing environmental explanations of intergenerational transmission of ADHD, such as parenting theories or psychological life-history theory.

Non-random Mating Patterns in Education, Mental, and Somatic Health: A Population Study on Within- and Cross-Trait Associations.

Partners resemble each other on many traits, such as health and education. The traits are usually studied one by one in data from established couples and with potential participation bias. We studied all Norwegian parents who had their first child between 2016 and 2020 (N=187,926) and the siblings of these parents. We analysed grade point averages (GPA), educational attainment (EA), and medical records with prospective diagnostic data on 10 mental and 10 somatic health conditions measured 10 to 5 years before childbirth. We found stronger partner similarity in mental (median r=0.14) than in somatic health conditions (median r=0.04), with ubiquitous cross-trait correlations for mental health conditions (median r=0.13). GPA correlated 0.43 and EA 0.47 between partners. High GPA or EA was associated with better mental (median r=-0.16) and somatic (median r=-0.08) health in partners. Elevated correlations for mental health (median r=0.25) in established couples indicated convergence. Analyses of data on siblings and in-laws revealed deviations from direct assortment, suggesting instead indirect assortment based on related traits. GPA and EA accounted for 30-40% of the partner correlations in health. This has implications for the distribution of risk factors among children and for studies of intergenerational transmission.

The p factor of psychopathology and personality in middle childhood: genetic and gestational risk factors.

BACKGROUND: A joint, hierarchical structure of psychopathology and personality has been reported in adults but should also be investigated at earlier ages, as psychopathology often develops before adulthood. Here, we investigate the joint factor structure of psychopathology and personality in eight-year-old children, estimate factor heritability and explore external validity through associations with established developmental risk factors. METHODS: Phenotypic and biometric exploratory factor analyses with bifactor rotation on genetically informative data from the Norwegian Mother, Father, and Child Cohort (MoBa) study. The analytic sub-sample comprised 10 739 children (49% girls). Mothers reported their children's symptoms of depression (Short Moods and Feelings Questionnaire), anxiety (Screen for Anxiety Related Disorders), attention-deficit/hyperactivity disorder inattention and hyperactivity, oppositional-defiant disorder, conduct disorder (Parent/Teacher Rating Scale for Disruptive Behavior Disorders), and Big Five personality (short Hierarchical Personality Inventory for Children). Developmental risk factors (early gestational age and being small for gestational age) were collected from the Medical Birth Registry. RESULTS: Goodness-of-fit indices favored a p factor model with three residual latent factors interpreted as negative affectivity, positive affectivity, and antagonism, whereas psychometric indices favored a one-factor model. ADE solutions fitted best, and regression analyses indicated a negative association between gestational age and the p factor, for both the one- and four-factor solutions. CONCLUSION: Correlations between normative and pathological traits in middle childhood mostly reflect one heritable and psychometrically interpretable p factor, although optimal fit to data required less interpretable residual latent factors. The association between the p factor and low gestational age warrants further study of early developmental mechanisms.

Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study.

Identifying mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) traits can inform interventions and provide insights into the role of parents in shaping their children's outcomes. We investigated whether genetic transmission and genetic nurture (environmentally mediated effects) underlie associations between polygenic scores indexing parental risk and protective factors and their offspring's ADHD traits. This birth cohort study included 19,506 genotyped mother-father-offspring trios from the Norwegian Mother, Father and Child Cohort Study. Polygenic scores were calculated for parental factors previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment, and cognitive performance. Mothers reported on their 8-year-old children's ADHD traits (n = 9,454 children) using the Parent/Teacher Rating Scale for Disruptive Behaviour Disorders. We found that associations between ADHD maternal and paternal polygenic scores and child ADHD traits decreased significantly when adjusting for the child polygenic score (pΔß = 9.95 × 10-17 for maternal and pΔß = 1.48 × 10-14 for paternal estimates), suggesting genetic transmission of ADHD risk. Similar patterns suggesting genetic transmission of risk were observed for smoking, educational attainment, and cognition. The maternal polygenic score for neuroticism remained associated with children's ADHD ratings even after adjusting for the child polygenic score, indicating genetic nurture. There was no robust evidence of genetic nurture for other parental factors. Our findings indicate that the intergenerational transmission of risk for ADHD traits is largely explained by the transmission of genetic variants from parents to offspring rather than by genetic nurture. Observational associations between parental factors and childhood ADHD outcomes should not be interpreted as evidence for predominantly environmentally mediated effects.

Estimating effects of parents' cognitive and non-cognitive skills on offspring education using polygenic scores.

Understanding how parents' cognitive and non-cognitive skills influence offspring education is essential for educational, family and economic policy. We use genetics (GWAS-by-subtraction) to assess a latent, broad non-cognitive skills dimension. To index parental effects controlling for genetic transmission, we estimate indirect parental genetic effects of polygenic scores on childhood and adulthood educational outcomes, using siblings (N = 47,459), adoptees (N = 6407), and parent-offspring trios (N = 2534) in three UK and Dutch cohorts. We find that parental cognitive and non-cognitive skills affect offspring education through their environment: on average across cohorts and designs, indirect genetic effects explain 36-40% of population polygenic score associations. However, indirect genetic effects are lower for achievement in the Dutch cohort, and for the adoption design. We identify potential causes of higher sibling- and trio-based estimates: prenatal indirect genetic effects, population stratification, and assortative mating. Our phenotype-agnostic, genetically sensitive approach has established overall environmental effects of parents' skills, facilitating future mechanistic work.

Modeling assortative mating and genetic similarities between partners, siblings, and in-laws.

Assortative mating on heritable traits can have implications for the genetic resemblance between siblings and in-laws in succeeding generations. We studied polygenic scores and phenotypic data from pairs of partners (n = 26,681), siblings (n = 2,170), siblings-in-law (n = 3,905), and co-siblings-in-law (n = 1,763) in the Norwegian Mother, Father and Child Cohort Study. Using structural equation models, we estimated associations between measurement error-free latent genetic and phenotypic variables. We found evidence of genetic similarity between partners for educational attainment (rg = 0.37), height (rg = 0.13), and depression (rg = 0.08). Common genetic variants associated with educational attainment correlated between siblings above 0.50 (rg = 0.68) and between siblings-in-law (rg = 0.25) and co-siblings-in-law (rg = 0.09). Indirect assortment on secondary traits accounted for partner similarity in education and depression, but not in height. Comparisons between the genetic similarities of partners and siblings indicated that genetic variances were in intergenerational equilibrium. This study shows genetic similarities between extended family members and that assortative mating has taken place for several generations.

Direct and Indirect Effects of Maternal, Paternal, and Offspring Genotypes: Trio-GCTA.

Indirect genetic effects from relatives may result in misleading quantifications of heritability, but can also be of interest in their own right. In this paper we propose Trio-GCTA, a model for separating direct and indirect genetic effects when genome-wide single nucleotide polymorphism data have been collected from parent-offspring trios. The model is applicable to phenotypes obtained from any of the family members. We discuss appropriate parameter interpretations and apply the method to three exemplar phenotypes: offspring birth weight, maternal relationship satisfaction, and paternal body-mass index, using real data from the Norwegian Mother, Father and Child Cohort Study (MoBa).

Parental Prenatal Symptoms of Depression and Offspring Symptoms of ADHD: A Genetically Informed Intergenerational Study.

Objective: The primary aim of the present study was to separate the direct effect of maternal prenatal depression on offspring ADHD from the passive transmission of genetic liability. Method: A children-of-twins and siblings design including 17,070 extended-family units participating in the Norwegian Mother and Child Cohort Study was used. Self-ratings were obtained from parents using the Symptom Checklist during pregnancy. Maternal ratings using Conner's Parent Rating Scale were obtained when the children were 5 years of age. Results: Genetic influences were important for explaining similarity between parents and offspring. There was also evidence for a maternal effect after accounting for genetic transmission (m = 0.06, 95% confidence interval [CI] = [0.02, 0.09]). Conclusion: Our results were consistent with hypotheses suggesting that maternal prenatal depression influences symptoms of ADHD in offspring. However, the effect was weak and a substantial portion of the association could be accounted for by shared genetic influences.

How important are parents in the development of child anxiety and depression? A genomic analysis of parent-offspring trios in the Norwegian Mother Father and Child Cohort Study (MoBa).

BACKGROUND: Many studies detect associations between parent behaviour and child symptoms of anxiety and depression. Despite knowledge that anxiety and depression are influenced by a complex interplay of genetic and environmental risk factors, most studies do not account for shared familial genetic risk. Quantitative genetic designs provide a means of controlling for shared genetics, but rely on observed putative exposure variables, and require data from highly specific family structures. METHODS: The intergenerational genomic method, Relatedness Disequilibrium Regression (RDR), indexes environmental effects of parents on child traits using measured genotypes. RDR estimates how much the parent genome influences the child indirectly via the environment, over and above effects of genetic factors acting directly in the child. This 'genetic nurture' effect is agnostic to parent phenotype and captures unmeasured heritable parent behaviours. We applied RDR in a sample of 11,598 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) to estimate parental genetic nurture separately from direct child genetic effects on anxiety and depression symptoms at age 8. We tested for mediation of genetic nurture via maternal anxiety and depression symptoms. Results were compared to a complementary non-genomic pedigree model. RESULTS: Parental genetic nurture explained 14% of the variance in depression symptoms at age 8. Subsequent analyses suggested that maternal anxiety and depression partially mediated this effect. The genetic nurture effect was mirrored by the finding of family environmental influence in our pedigree model. In contrast, variance in anxiety symptoms was not significantly influenced by common genetic variation in children or parents, despite a moderate pedigree heritability. CONCLUSIONS: Genomic methods like RDR represent new opportunities for genetically sensitive family research on complex human traits, which until now has been largely confined to adoption, twin and other pedigree designs. Our results are relevant to debates about the role of parents in the development of anxiety and depression in children, and possibly where to intervene to reduce problems.

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.

Mechanisms linking parental educational attainment with child ADHD, depression, and academic problems: a study of extended families in The Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Low educational attainment in parents is associated with child psychopathology. It is not clear whether the associations are due to risk factors that family members share or due to effects of maternal or paternal education on the offspring. We investigate whether associations between maternal and paternal educational attainment and child symptoms of attention deficit/hyperactivity disorder (ADHD), depression, and academic problems are due to shared genetic factors, shared family environmental factors, or effects of the parental phenotype educational attainment itself. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). The sample comprised 34,958 children (17,128 girls) in 28,372 extended-family units. We used data from related nuclear families linked by siblings in the parent generation. We applied a quasi-experimental extended children-of-twins design that included siblings in both generations and took account of nonrandom mating by including partners. Educational attainment was self-reported by mothers and fathers. Mothers reported children's symptoms of ADHD, symptoms of depression, and academic problems by questionnaire when the children were 8 years old. RESULTS: Children of lowly educated parents scored higher on all outcomes and had an approximate doubling of the risk of high symptom levels. The association between maternal and paternal educational attainment and child symptoms of ADHD and academic problems persisted after controlling for shared genetic and family environmental factors. Phenotypic transmission to depression was weaker and in the best fitting model fully explained by genetic factors shared by the two generations. CONCLUSIONS: Associations between educational attainment of mothers and fathers and child symptoms of ADHD and academic problems could not be ascribed to shared familial risk factors, whereas associations with symptoms of depression could. Parental education or resources and behaviors resulting from low education might be targets of interventions aimed at reducing symptoms of ADHD and academic problems.

Does prenatal stress amplify effects of postnatal maternal depressive and anxiety symptoms on child problem behavior?

Emerging evidence suggests that prenatal stress does not solely undermine child functioning but increases developmental plasticity to both negative and positive postnatal experiences. Here we test this proposition using the Norwegian Mother and Child Cohort study while implementing an extreme-group (i.e., high vs. low prenatal stress) design (n = 27,889 children for internalizing and n = 27,892 for externalizing problems). To measure prenatal stress, mothers reported on depressive and anxiety symptoms at gestational weeks 17 and 30 and of stressful life events at gestational week 30. We then evaluated whether, collectively, such prenatal stress amplified the effect of mothers' postnatal depressive and anxiety symptoms on children's internalizing and externalizing behavior problems at age 5 years. Results showed prenatal stress amplified effects of postnatal maternal depression/anxiety on child internalizing but not externalizing behavior, with some indication that this Prenatal-Stress-×-Postnatal-Maternal-Depression interaction proved more consistent with differential susceptibility than diathesis stress thinking: Children exposed to prenatal stress evinced greater internalizing problems if exposed to more postnatal maternal depressive/anxiety symptoms and, somewhat less strongly, displayed less internalizing problems if they experienced lower postnatal maternal depressive/anxiety symptoms. However, analyses using the whole sample instead of extreme groups yielded opposing results with children exposed to the least prenatal stress evincing greater sensitivity to postnatal maternal depressive/anxiety symptoms with regards to externalizing and internalizing behavior. Taken together, it appears that prenatal stress may have differing effects on plasticity depending on prenatal stress severity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Development of ADHD symptoms in preschool children: Genetic and environmental contributions.

We examined genetic and environmental contributions to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) in preschool children. ADHD symptoms in siblings at 1.5, 3, and 5 years of age were investigated in a population-based sample from the prospective Norwegian Mother and Child Cohort Study. The longitudinal contributions of additive genetic, shared, twin-specific, and unique environmental influences were estimated using biometric structural equation models. Heritability of ADHD symptoms ranged from 54% to 70%. There was evidence of partially new genetic influences at successive ages, with genetic correlations ranging from .58 to .89. Contributions from shared environmental factors and twin-specific factors were minor. The importance of unique environmental effects appeared to increase across ages, and was mostly specific to a given age. There was no evidence suggesting that this pattern differs across males and females. Symptoms of ADHD are highly heritability in young children from as early as 1.5 years of age. Longitudinal stability of ADHD symptoms is mainly attributable to genetic influences, but there is also some evidence for age-specific genetic influences. These findings contribute to our understanding of development of ADHD early in life, and can guide future molecular genetics studies.

Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study.

BACKGROUND: Maternal prenatal depression is a known risk factor for early-life psychopathology among offspring; however, potential risk transmission mechanisms need to be distinguished. We aimed to test the relative importance of passive genetic transmission, direct exposure, and indirect exposure in the association between maternal prenatal depressive symptoms and early-life internalising and externalising psychopathology in offspring. METHODS: We used structural equation modelling of phenotypic data and genetically informative relationships from the families of participants in the Norwegian Mother and Child Birth Cohort Study (MoBa). The analytic subsample of MoBa used in the current study comprises 22 195 mothers and 35 299 children. We used mothers' self-reported depressive symptoms during pregnancy, as captured by the Symptom Checklist, and their reports of symptoms of psychopathology in their offspring during the first few years of life (measured at 18, 36, and 60 months using the Child Behavior Checklist). FINDINGS: Maternal prenatal depressive symptoms were found to be associated with early-life psychopathology primarily via intergenerationally shared genetic factors, which explained 41% (95% CI 36-46) of variance in children's internalising problems and 37% (30-44) of variance in children's externalising problems. For internalising problems, phenotypic transmission also contributed significantly, accounting for 14% (95% CI 5-19) of the association, but this contribution was found to be explained by exposure to concurrent maternal depressive symptoms, rather than by direct exposure in utero. INTERPRETATION: Associations between maternal prenatal depressive symptoms and offspring behavioural outcomes in early childhood are likely to be at least partially explained by shared genes. This genetic confounding should be considered when attempting to quantify risks posed by in-utero exposure to maternal depressive symptoms. FUNDING: UK Economic and Social Research Council, Norwegian Research Council, Norwegian Ministries of Health and Care Services, and Education & Research, Wellcome Trust, Royal Society, and National Institute for Health Research.

Revisiting the Children-of-Twins Design: Improving Existing Models for the Exploration of Intergenerational Associations.

Datasets comprising twins and their children can be a useful tool for understanding the nature of intergenerational associations between parent and offspring phenotypes. In the present article we explore structural equation models previously used to analyse Children-of-Twins data, highlighting some limitations and considerations. We then present new variants of these models, showing that extending the models to include multiple offspring per parent addresses several of the limitations discussed. Accompanying the updated models, we provide power calculations and demonstrate with application to simulated data. We then apply to intergenerational analyses of height and weight, using a sub-study of the Norwegian Mother and Child Cohort (MoBa); the Intergenerational Transmission of Risk (IToR) project, wherein all kinships in the MoBa data have been identified (a children-of-twins-and-siblings study). Finally, we consider how to interpret the findings of these models and discuss future directions.

Maternal alcohol use during pregnancy and offspring attention-deficit hyperactivity disorder (ADHD): a prospective sibling control study.

Background: Maternal alcohol use during pregnancy has repeatedly been associated with development of attention-deficit hyperactivity disorder (ADHD) in the offspring. It is, however not known whether this reflects a direct casual intra-uterine effect or a non-causal relationship due to confounding. We used three different approaches to control for measured and unmeasured confounding: statistical adjustment for covariates, negative control comparison against maternal pre-pregnancy alcohol use, and comparison among differentially exposed siblings. Methods: The sample comprised 114 247 children (34 283 siblings) from 94 907 mothers, recruited to the Norwegian Mother and Child Birth Cohort Study between 1999 and 2008. Self-reported measurements of alcohol use were obtained in week 30 during the pregnancy. Mothers rated offspring ADHD symptoms at 5 years on two measures. Clinical ADHD diagnoses were obtained from the Norwegian Patient Registry. Results: We found an overall positive association between maternal alcohol use during pregnancy and offspring ADHD symptoms, which was only marginally attenuated after inclusion of measured covariates. Both the negative control and the sibling comparison analysis further attenuated the estimated association, but it remained greater than zero [ß = 0.017, 95% confidence interval (CI) = 0.005-0.030). No association was found between maternal alcohol use during pregnancy and offspring ADHD diagnosis. Conclusions: For offspring ADHD symptoms we found a weak, but possibly causal association with maternal alcohol use during pregnancy, but no such effect was observed for clinical ADHD diagnosis.