ABSTRACT
Objective. Fathers are of great importance for healthy child development. This randomized controlled study investigated the longer-term effects of an intervention using a soft baby carrier on fathers' observed sensitive caregiving, involvement, and oxytocin and cortisol levels. Design. First-time fathers were randomly assigned to use a baby carrier (n = 41) or baby seat (n = 39) and were asked to use the carrier or seat for at least 6 h per week for 3 weeks. Pretest (M child age = 2.67 months), posttest (M child age = 3.99 months), and follow-up (M child age = 8.25 months) father data were collected. Results. No intervention effects of baby carrier use on fathers' sensitivity, involvement, and oxytocin or cortisol levels at follow-up emerged. Unexpectedly, fathers in the baby seat condition reported an increase in the amount of time spent with the infant. Fathers' sensitivity and oxytocin levels decreased over time, while cortisol levels increased over time, irrespective of condition. Conclusions. This study showed less optimal hormonal levels in fathers over time, suggesting that support during the first months of fatherhood is needed. Furthermore, use of a baby seat may have contributed to fathers enjoying their time with their infant and consequently their involvement in child caregiving.
ABSTRACT
Mood variability, the day-to-day fluctuation in mood, differs between individuals and develops during adolescence. Because adolescents show higher mood variability and average mood than children and adults, puberty might be a potential biological mechanism underlying this increase. The goal of this preregistered developmental study was to examine the neural and hormonal underpinnings of adolescent-specific within-person changes in mood variability, with a specific focus on testosterone, cortisol, pubertal status, and resting-state functional brain connectivity. Data from two longitudinal cohorts were used: the L-CID twin study (aged 7-13, N at the first timepoint = 258) and the accelerated Leiden Self-Concept study (SC; aged 11-21, N at the first timepoint = 138). In both studies resting-state functional magnetic resonance imaging (rs-fMRI) data was collected, as well as daily mood. Additionally, in the SC study self-reported puberty testosterone and cortisol were collected. Random intercept cross-lagged panel models (RI-CLPM) were used to study the within-person relations between these biological measures and mood variability and average mood. Mood variability and average mood peaked in adolescence and testosterone levels and self-reported puberty also showed an increase. Connectivity between prefrontal cortex (dlPFC and vmPFC) and subcortical regions (caudate, amygdala) decreased across development. Moreover, higher testosterone predicted average negative mood at the next time point, but not vice versa. Further, stronger vmPFC-amygdala functional connectivity predicted decreases in mood variability. Here, we show that brain connectivity during development is an important within-person biological mechanism of the development of mood in adolescents. PRACTITIONER POINTS: Mood variability peaks in adolescence. Within-person changes in testosterone predict within-person changes in mood. Within-person changes in vmPFC-amygdala connectivity predict within-person changes in mood variability.
Subject(s)
Affect , Hydrocortisone , Magnetic Resonance Imaging , Puberty , Testosterone , Humans , Adolescent , Child , Male , Testosterone/blood , Affect/physiology , Female , Hydrocortisone/blood , Hydrocortisone/metabolism , Longitudinal Studies , Puberty/physiology , Young Adult , Brain/diagnostic imaging , Brain/growth & development , Brain/physiology , Adult , Connectome , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , Prefrontal Cortex/growth & development , Amygdala/diagnostic imaging , Amygdala/physiology , Amygdala/growth & development , Adolescent Development/physiologyABSTRACT
Numerous theories suggest that parents and adolescents influence each other in diverse ways; however, whether these influences differ between subgroups or are unique to each family remains uncertain. Therefore, this study explored whether data-driven subgroups of families emerged that exhibited a similar daily interplay between parenting and adolescent affective well-being. To do so, Subgrouping Group Iterative Multiple Model Estimation (S-GIMME) was used to estimate family-specific dynamic network models, containing same- and next-day associations among five parenting practices (i.e., warmth, autonomy support, psychological control, strictness, monitoring) and adolescent positive and negative affect. These family-specific networks were estimated for 129 adolescents (Mage = 13.3, SDage = 1.2, 64% female, 87% Dutch), who reported each day on parenting and their affect for 100 consecutive days. The findings of S-GIMME did not identify data-driven subgroups sharing similar parenting-affect associations. Instead, each family displayed a unique pattern of temporal associations between the different practices and adolescent affect. Thus, the ways in which parenting practices were related to adolescents' affect in everyday life were family specific.
Subject(s)
Adolescent Behavior , Parenting , Humans , Adolescent , Female , Infant , Male , Parenting/psychology , Parents/psychology , Parent-Child Relations , Adolescent Behavior/psychologyABSTRACT
[This corrects the article DOI: 10.3389/fnbeh.2022.942363.].
ABSTRACT
This randomized, double-blind, placebo-controlled within-subject study examined the effects of intranasal administration of oxytocin and vasopressin on fathers' sensitive and challenging parenting behaviors. Furthermore, we examined the moderating role of fathers' early childhood experiences. The sample consisted of 70 fathers with their 2- to 12-month-old infants. All fathers were assigned to each of the three experimental sessions (oxytocin, vasopressin, and placebo), on three separate days, with random order and intervening periods of one to two weeks. Sensitive and challenging parenting behaviors (CPB) were observed during a 10-minute free play task. Results showed no effects of vasopressin administration on paternal sensitivity. Fathers in the oxytocin condition were less sensitive than fathers in the placebo condition, and this effect was moderated by fathers' own childhood experiences: Fathers who reported higher levels of experienced parental love withdrawal were less sensitive in the oxytocin condition as compared to the placebo condition, whereas fathers with less experienced parental love withdrawal showed no difference in sensitivity between the oxytocin and placebo condition. No effects were found of oxytocin and vasopressin administration on fathers' CPB. Our results, although partly unexpected, are largely in line with previous literature showing that oxytocin administration can exert negative effects in individuals with adverse childhood experiences.
Subject(s)
Adverse Childhood Experiences , Oxytocin , Parenting , Paternal Behavior , Vasopressins , Administration, Intranasal , Adverse Childhood Experiences/psychology , Fathers , Humans , Infant , Male , Oxytocin/pharmacology , Parenting/psychology , Paternal Behavior/drug effects , Paternal Behavior/psychology , Role , Vasopressins/pharmacologyABSTRACT
In a randomized double-blind within-subject control study we investigated the effects of oxytocin and vasopressin administration on neural reactivity to infant cry sounds in 70 first-time fathers in the first year of fatherhood. Additionally, we examined whether effects of oxytocin and vasopressin administration on neural reactivity were moderated by fathers' early childhood experiences. Neural reactivity to infant cry sounds (versus control sounds) was measured using functional magnetic resonance imaging (fMRI). Furthermore, participants reported on their childhood experiences of parental harsh discipline and parental love withdrawal. Whole brain analyses revealed no significant effect of vasopressin or oxytocin administration on neural activation in response to infant cry sounds. Region of interest analyses showed decreased amygdala activation in both the oxytocin condition and the vasopressin condition as compared to placebo. We found no moderating effects of fathers' early childhood experiences. Our findings suggest that oxytocin administration may decrease feelings of anxiety or aversion to a crying infant. Whether decreased amygdala activation after vasopressin administration might be explained by contextual factors (e.g., absence of high levels of threat, unfamiliarity of the infant) or represents an affiliative response to infant distress warrants further investigation. Findings of the present study showed that oxytocin and vasopressin are important hormones implicated in neural models of infant cry perception in fatherhood.
Subject(s)
Crying , Oxytocin , Administration, Intranasal , Brain , Child, Preschool , Fathers , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Oxytocin/pharmacology , Vasopressins/pharmacologyABSTRACT
Introduction: Parenthood can be experienced as a pleasant but challenging period for parents, possibly accompanied by parenting stress. Early parenthood in particular is a vulnerable period as many parents experience biological and psychosocial changes related to new parenthood. Previous studies have shown that parenting stress is related to child behavior problems, but few studies have investigated the transactional relations across time between parenting stress and child internalizing and externalizing outcomes separately, examining within-person changes. The first aim of this study was to examine the transactional within-person associations of parenting stress and child internalizing and externalizing behavior problems across childhood from age 9 months to 9 years. As a second aim, we examined parenting as a possible underlying mechanism of the transactional associations by testing whether parental warmth and hostility mediate within-person associations of parenting stress and child behavior across time. Method: Data were analyzed from the Growing Up in Ireland longitudinal child cohort study including 7,208 caregiver-child dyads at wave 1 (child's age 9 months), who were followed at child's age three (wave 2), five (wave 3), and 9 years (wave 5). Primary caregiver's and child's age and gender, household income, occupational status, educational status, partner status, and cultural background were covariates assessed at all waves. Data were analyzed using a random intercept cross-lagged panel model (CLPM) in R-lavaan. Results: Bidirectional relations between parenting stress and child behavior were found for both internalizing and externalizing behavior from age 5 to 9, but not for earlier time points. Discussion: Our results did not indicate mediating effects of parental warmth or parental hostility in the associations between parenting stress and child behavior problems. Therefore, we conclude that parenting stress and child internalizing as well as parenting stress and child externalizing behaviors have transactional associations from child's age 5 to 9 years. Future research examining transactional associations of parenting stress and child behaviors should investigate possible other mediations taking a within-person approach by utilizing the RI-CLPM.
ABSTRACT
This longitudinal study examined developmental trajectories of infant sleep problems from 3 to 24 months old and investigated associations with infant-parent attachment security and dependency. In a sample of 107 Israeli families, number and duration of infant nighttime awakenings were measured at 3, 6, 9, and 24 months old, using mothers' and fathers' reports on the Brief Infant Sleep Questionnaire (BISQ). Infant-parent attachment security and infant-parent dependency was assessed at 24 months old, using the observer Attachment Q-Sort procedure (AQS) with both parents. Latent growth curve models showed a non-linear decline in number and duration of infant nighttime awakenings over time. A higher number and longer duration of infant nighttime awakenings at 3 months were associated with higher infant-father attachment security at 24 months. In contrast, longer infant nighttime awakenings at 3 months were predictive of lower infant-mother attachment security at 24 months. A steeper decrease in duration of infant nighttime awakenings was associated with higher infant-father attachment security and lower infant-mother attachment security. As a potential mechanism, paternal involvement in nighttime caregiving was explored in relation to infant-father attachment security. Results of our post-hoc analyses revealed no significant associations between paternal involvement in nighttime caregiving and infant-father attachment security. Our results highlight the need to examine potential mechanisms explaining the divergent associations of infant sleep problems with infant-mother and infant-father attachment security in future research.
Subject(s)
Father-Child Relations , Mothers , Child, Preschool , Fathers , Female , Humans , Infant , Longitudinal Studies , Male , Mother-Child Relations , Object AttachmentABSTRACT
BACKGROUND: Young people with disabilities are more at risk of experiencing loneliness in later life than their typically developing peers. AIM: To identify those who become lonely in later life, trajectories of perceived parent and peer support from adolescence to adulthood of young people with a visual impairment were studied. METHODS: A total of 316 adolescents (Mâ¯=â¯18 years; SDâ¯=â¯6.5) enrolled in a cohort study in 1996; 205 of them participated in 2005, 178 in 2010, and 161 in 2016. Latent growth curve models were fitted to the data. RESULTS: Perceived parent support followed a linear decreasing course. No association was found between perceived parent support and loneliness in later life. For perceived peer support a quadratic growth pattern was found, with an increase in peer support up to age 27, and thereafter a decrease. Both the initial level and the rate of change in perceived peer support significantly predicted loneliness in adulthood. CONCLUSIONS: The course of peer support is a better indicator for the risk of loneliness in later life than support from parents. Normative life transitions may affect the already vulnerable social support for young people with a visual impairment. This study highlights the importance of establishing and maintaining peer relationships throughout life.
Subject(s)
Loneliness/psychology , Parents , Peer Group , Social Support , Vision Disorders/psychology , Adolescent , Adult , Female , Humans , Longitudinal Studies , Male , Netherlands , Social Networking , Young AdultABSTRACT
The development of problem behavior in children is associated with exposure to environmental factors, including the maternal environment. Both are influenced by genetic factors, which may also be correlated, that is, environmental risk and problem behavior in children might be influenced by partly the same genetic factors. In addition, environmental and genetic factors could interact with each other increasing the risk of problem behavior in children. To date, limited research investigated these mechanisms in a genome-wide approach. Therefore, the goal of this study was to investigate the association between genetic risk for psychiatric and related traits, as indicated by polygenetic risk scores (PRSs), exposure to previously identified maternal risk factors, and problem behavior in a sample of 1,154 children from the Amsterdam Born Children and their Development study at ages 5-6 and 11-12 years old. The PRSs were derived from genome-wide association studies (GWASs) on schizophrenia, major depressive disorder, neuroticism, and wellbeing. Regression analysis showed that the PRSs were associated with exposure to multiple environmental risk factors, suggesting passive gene-environment correlation. In addition, the PRS based on the schizophrenia GWAS was associated with externalizing behavior problems in children at age 5-6. We did not find any association with problem behavior for the other PRSs. Our results indicate that genetic predispositions for psychiatric disorders and wellbeing are associated with early environmental risk factors for children's problem behavior.
Subject(s)
Child Behavior Disorders/psychology , Mental Disorders/etiology , Mothers/psychology , Child , Child, Preschool , Depressive Disorder, Major/etiology , Depressive Disorder, Major/genetics , Female , Genetic Association Studies/methods , Genome-Wide Association Study/methods , Health , Humans , Male , Mental Disorders/genetics , Multifactorial Inheritance/genetics , Neuroticism/physiology , Psychiatric Status Rating Scales , Regression Analysis , Risk Factors , Schizophrenia/etiology , Schizophrenia/geneticsABSTRACT
BACKGROUND: Previous research has mostly focused on the hormonal, behavioral and neural correlates of maternal caregiving. We present a randomized, double-blind, placebo-controlled within-subject design to examine the effects of intranasal administration of oxytocin and vasopressin on parenting behavior and the neural and behavioral responses to infant cry sounds and infant threat. In addition, we will test whether effects of oxytocin and vasopressin administration are moderated by fathers' early childhood experiences. METHODS: Fifty-five first-time fathers of a child between two and seven months old will participate in three experimental sessions with intervening periods of one to two weeks. Participants self-administer oxytocin, vasopressin or a placebo. Infant-father interactions and protective parenting responses are observed during play. Functional Magnetic Resonance Imaging (fMRI) is used to examine the neural processing of infant cry sounds and infant threat. A handgrip dynamometer is used to measure use of handgrip force when listening to infant cry sounds. Participants report on their childhood experiences of parental love-withdrawal and abuse and neglect. DISCUSSION: The results of this study will provide important insights into the hormonal, behavioral and neural correlates of fathers' parenting behavior during the early phase of fatherhood. TRIAL REGISTRATION: Dutch Trial Register: NTR (ID: NL8124); Date registered: October 30, 2019.
Subject(s)
Brain/drug effects , Fathers , Neurophysins/administration & dosage , Oxytocin/administration & dosage , Paternal Behavior/drug effects , Protein Precursors/administration & dosage , Vasopressins/administration & dosage , Administration, Intranasal , Adult , Brain/diagnostic imaging , Child , Child, Preschool , Double-Blind Method , Female , Hand Strength/physiology , Humans , Infant , Infant Behavior , Magnetic Resonance Imaging/methods , Male , Randomized Controlled Trials as Topic , Research DesignABSTRACT
Adverse childhood experiences (ACEs) have an impact on women's adaptation to parenthood, but mechanisms are poorly understood. Autonomic nervous system reactivity was tested as a potential mediating mechanism in a sample of 193 at-risk primiparous women. ACEs were measured retrospectively during pregnancy. A baby cry-response task was administered during pregnancy while indicators of sympathetic reactivity (pre-ejection period; PEP) and parasympathetic reactivity (respiratory sinus arrhythmia; RSA) were recorded. Parenting self-efficacy, anxiety, and depressive symptoms were measured during pregnancy and 1 year after giving birth. Harsh discipline was measured 2 years after giving birth. Structural equation modeling was employed to test whether baseline PEP and RSA and reactivity mediated links between ACEs and postnatal outcomes, adjusted for prenatal variables. High ACEs predicted less RSA reactivity (p = .02), which subsequently predicted increases in depressive symptoms (p = .03). The indirect effect was not significant (p = .06). There was no indirect link between high ACEs and harsh parenting through PEP nor RSA (n = 98). The parasympathetic nervous system may be involved in negative affective responses in the transition to parenthood among women exposed to childhood trauma.
ABSTRACT
Executive Functions (EFs) have been associated with aggression in children and adolescents. EFs as higher-order cognitive abilities are assumed to affect cognitive functions such as Social Information Processing (SIP). We explored SIP skills as a mediating mechanism linking EFs to aggression in adolescents with mild to borderline intellectual disability (MBID with IQ from 50-84), a high risk group for aggressive behaviors and EF impairments. A total of 153 adolescents (Mage = 15.24, SD = 1.35; 54% male) with MBID participated. Focused attention, behavioral inhibition, and working memory were tested with multiple neurocognitive tasks to define latent EF constructs. Participants responded to a video-based SIP task. A latent construct for aggression was defined by caretaker, teacher, and adolescent self-reports of aggression (Child Behavior Check List, Teacher Report Form, and Youth Self Report). Structural equation modeling was performed to test mediation. Results were consistent with mediation of the relation between focused attention and aggression by SIP, namely via hostile interpretations and self-efficacy for aggression. Behavioral inhibition was linked to aggression, but this relation was not mediated by SIP. The relation between working memory and aggression was mediated by SIP, namely via hostile interpretations, aggressive response generation and via self-efficacy for aggressive responses. Bearing the cross-sectional design in mind, support was found for SIP skills as a mechanism linking EFs, in particular focused attention and working memory, to aggression, providing a viable explanation for the high vulnerability of adolescents with MBID for aggression.
Subject(s)
Aggression/psychology , Cognition/physiology , Executive Function/physiology , Intellectual Disability/psychology , Social Skills , Adolescent , Cross-Sectional Studies , Female , Humans , MaleABSTRACT
This study tested experimentally whether the combination of a history of childhood abuse and confrontation with difficult infant temperament is associated with negative changes in parenting self-efficacy. First-time pregnant women (N = 243) participated in the Adult Attachment Interview, which was used to assess the occurrence of abuse by parents in childhood and unresolved representations, and completed a task asking them to respond to infant cries. Sixty of the 243 participants (25%) experienced childhood abuse, mostly physical or sexual. The task simulated infant temperamental difficulty by manipulating soothing success in order to reflect an easy-to-soothe (80% soothing success) and a difficult-to-soothe infant (20% soothing success). Both after baseline and after each of the two stimulus series women assessed their parenting self-efficacy. Women who reported childhood abuse did not differ from women who reported no childhood abuse in parenting self-efficacy at baseline or in response to the easy-to-soothe infant (relative to baseline), but decreased more in parenting self-efficacy following the difficult-to-soothe infant. Effects did not vary according to resolution of trauma. These findings suggest that in response to infant temperamental difficulty, women who experienced childhood abuse may more easily lose confidence in their parenting abilities, which underlines the importance of preparing at-risk women for the possible challenges that come along with parenthood.
Subject(s)
Child Abuse/psychology , Mother-Child Relations/psychology , Parenting , Resilience, Psychological , Self Efficacy , Adult , Child , Female , Humans , Pregnancy , Risk Factors , Self ReportABSTRACT
Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
Subject(s)
Extraversion, Psychological , Genome-Wide Association Study , Personality/genetics , Cohort Studies , Humans , Multifactorial Inheritance/genetics , Polymorphism, Single Nucleotide/genetics , Risk FactorsABSTRACT
Anger is an emotion consisting of feelings of variable intensity ranging from mild irritation to intense fury. High levels of trait anger are associated with a range of psychiatric, interpersonal, and health problems. The objectives of this study were to explore heterogeneity of anger as measured by the Spielberger Trait Anger Scale (STAS), and to assess the association of the different anger facets with a selection of psychiatric disorders covering externalizing and internalizing problems, personality disorders, and substance use. Factor mixture models differentiated between a high and low scoring class (28% vs. 72%), and between three factors (anger-temperament, anger-reaction, and immediacy of an anger response). Whereas all psychiatric scales correlated significantly with the STAS total score, regressing the three STAS factors on psychiatric behaviors model showed a more detailed pattern. Only borderline affect instability and depression were significantly associated with all three factors in both classes whereas other problem behaviors were associated only with 1 or 2 of the factors. Alcohol problems were associated with immediacy only in the high scoring class, indicating a non-linear relation in the total sample. Taking into account these more specific associations is likely to be beneficial when investigating differential treatment strategies.
Subject(s)
Alcohol-Related Disorders/physiopathology , Anger/physiology , Anxiety Disorders/physiopathology , Attention Deficit Disorder with Hyperactivity/physiopathology , Borderline Personality Disorder/physiopathology , Depression/physiopathology , Registries/statistics & numerical data , Temperament/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Alcohol-Related Disorders/epidemiology , Anxiety Disorders/epidemiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Borderline Personality Disorder/epidemiology , Depression/epidemiology , Diseases in Twins/epidemiology , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Neuroticism , Young AdultABSTRACT
Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE = 0.12, P = 0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P = 7.58 × 10(-7) ). This first GWAS of AD using the AUDIT measure found results consistent with previous genetic studies using DSM diagnosis: concordance in heritability estimates and direction of SNPs effect and overlap with top hits from previous GWAS. Thus, the use of appropriate questionnaires may represent cost-effective strategies to phenotype samples in large-scale biobanks or other population-based datasets.
Subject(s)
Alcoholism/genetics , Twins/genetics , Adult , Alcoholism/epidemiology , Case-Control Studies , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Netherlands/epidemiology , Polymorphism, Single Nucleotide , Quantitative Trait LociABSTRACT
IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.
Subject(s)
Anxiety Disorders/genetics , Cell Adhesion Molecules, Neuronal/genetics , Depressive Disorder, Major/genetics , Personality/genetics , Adaptor Proteins, Signal Transducing , Anxiety Disorders/psychology , Cell Adhesion Molecules , Depressive Disorder, Major/psychology , Genetic Predisposition to Disease , Genome-Wide Association Study , Guanylate Kinases , Humans , Multifactorial Inheritance , Neuroticism , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Variation in the liver enzyme levels in humans is moderately heritable, as indicated by twin-family studies. At present, genome-wide association studies have traced <2% of the variance back to genome-wide significant single-nucleotide polymorphisms (SNPs). We estimated the SNP-based heritability of levels of three liver enzymes (gamma-glutamyl transferase (GGT); alanine aminotransferase (ALT); and aspartate aminotransferase (AST)) using genome-wide SNP data in a sample of 5421 unrelated Dutch individuals. Two estimation methods for SNP-based heritability were compared, one based on the distant genetic relatedness among all subjects as summarized in a Genetic Relatedness Matrix (GRM), and the other one based on density estimation (DE). The DE method was also applied to meta-analysis results on GGT and ALT. GRM-derived SNP-based heritability estimates were significant for GGT (16%) and AST (11%), but not for ALT (6%). DE estimates in the same sample varied as a function of pruning and were around 23% for all liver enzymes. Application of the DE approach to meta-analysis results for GGT and ALT gave SNP-based heritability estimates of 6 and 3%. The significant results in the Dutch sample indicate that genome-wide SNP platforms contain substantial information regarding the underlying genetic variation in the liver enzyme levels. A major part of this genetic variation remains however undetected. SNP-based heritability estimates, based on meta-analysis results, may point at substantial heterogeneity among cohorts contributing to the meta-analysis. This type of analysis may provide useful information to guide future gene searches.
Subject(s)
Alanine Transaminase/genetics , Aspartate Aminotransferases/genetics , Inheritance Patterns , Liver/enzymology , Polymorphism, Single Nucleotide , gamma-Glutamyltransferase/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Female , Genome, Human , Genome-Wide Association Study , Humans , Liver/chemistry , Male , Meta-Analysis as Topic , Middle Aged , Phenotype , gamma-Glutamyltransferase/metabolismABSTRACT
Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.