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1.
J Youth Adolesc ; 53(4): 982-997, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38055136

RESUMEN

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.


Asunto(s)
Conducta del Adolescente , Responsabilidad Parental , Humanos , Adolescente , Femenino , Lactante , Masculino , Responsabilidad Parental/psicología , Padres/psicología , Relaciones Padres-Hijo , Conducta del Adolescente/psicología
3.
Horm Behav ; 142: 105175, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35430502

RESUMEN

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.


Asunto(s)
Experiencias Adversas de la Infancia , Oxitocina , Responsabilidad Parental , Conducta Paterna , Vasopresinas , Administración Intranasal , Experiencias Adversas de la Infancia/psicología , Padre , Humanos , Lactante , Masculino , Oxitocina/farmacología , Responsabilidad Parental/psicología , Conducta Paterna/efectos de los fármacos , Conducta Paterna/psicología , Rol , Vasopresinas/farmacología
4.
Psychoneuroendocrinology ; 140: 105731, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35334388

RESUMEN

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.


Asunto(s)
Llanto , Oxitocina , Administración Intranasal , Encéfalo , Preescolar , Padre , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Oxitocina/farmacología , Vasopresinas/farmacología
5.
Front Behav Neurosci ; 16: 942363, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36590923

RESUMEN

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.

6.
Infant Behav Dev ; 65: 101653, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34655886

RESUMEN

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.


Asunto(s)
Relaciones Padre-Hijo , Madres , Preescolar , Padre , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Relaciones Madre-Hijo , Apego a Objetos
7.
Res Dev Disabil ; 101: 103634, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32315928

RESUMEN

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 (M = 18 years; SD = 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.


Asunto(s)
Soledad/psicología , Padres , Grupo Paritario , Apoyo Social , Trastornos de la Visión/psicología , Adolescente , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Países Bajos , Red Social , Adulto Joven
8.
Am J Med Genet B Neuropsychiatr Genet ; 183(1): 17-25, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31444904

RESUMEN

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.


Asunto(s)
Trastornos de la Conducta Infantil/psicología , Trastornos Mentales/etiología , Madres/psicología , Niño , Preescolar , Trastorno Depresivo Mayor/etiología , Trastorno Depresivo Mayor/genética , Femenino , Estudios de Asociación Genética/métodos , Estudio de Asociación del Genoma Completo/métodos , Salud , Humanos , Masculino , Trastornos Mentales/genética , Herencia Multifactorial/genética , Neuroticismo/fisiología , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Factores de Riesgo , Esquizofrenia/etiología , Esquizofrenia/genética
9.
BMC Psychol ; 7(1): 81, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31843012

RESUMEN

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.


Asunto(s)
Encéfalo/efectos de los fármacos , Padre , Neurofisinas/administración & dosificación , Oxitocina/administración & dosificación , Conducta Paterna/efectos de los fármacos , Precursores de Proteínas/administración & dosificación , Vasopresinas/administración & dosificación , Administración Intranasal , Adulto , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Método Doble Ciego , Femenino , Fuerza de la Mano/fisiología , Humanos , Lactante , Conducta del Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación
10.
Child Neuropsychol ; 25(5): 573-598, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30010484

RESUMEN

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.


Asunto(s)
Agresión/psicología , Cognición/fisiología , Función Ejecutiva/fisiología , Discapacidad Intelectual/psicología , Habilidades Sociales , Adolescente , Estudios Transversales , Femenino , Humanos , Masculino
11.
Dev Psychopathol ; 31(1): 127-141, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30585566

RESUMEN

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.

12.
PLoS One ; 11(2): e0141801, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26848573

RESUMEN

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.


Asunto(s)
Maltrato a los Niños/psicología , Relaciones Madre-Hijo/psicología , Responsabilidad Parental , Resiliencia Psicológica , Autoeficacia , Adulto , Niño , Femenino , Humanos , Embarazo , Factores de Riesgo , Autoinforme
13.
Behav Genet ; 46(2): 170-82, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26362575

RESUMEN

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.


Asunto(s)
Extraversión Psicológica , Estudio de Asociación del Genoma Completo , Personalidad/genética , Estudios de Cohortes , Humanos , Herencia Multifactorial/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo
14.
Psychiatry Res ; 230(2): 553-60, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26454404

RESUMEN

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.


Asunto(s)
Trastornos Relacionados con Alcohol/fisiopatología , Ira/fisiología , Trastornos de Ansiedad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno de Personalidad Limítrofe/fisiopatología , Depresión/fisiopatología , Sistema de Registros/estadística & datos numéricos , Temperamento/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastornos Relacionados con Alcohol/epidemiología , Trastornos de Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno de Personalidad Limítrofe/epidemiología , Depresión/epidemiología , Enfermedades en Gemelos/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Neuroticismo , Adulto Joven
15.
Am J Med Genet B Neuropsychiatr Genet ; 168(8): 739-48, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26365420

RESUMEN

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.


Asunto(s)
Alcoholismo/genética , Gemelos/genética , Adulto , Alcoholismo/epidemiología , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Países Bajos/epidemiología , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo
16.
JAMA Psychiatry ; 72(7): 642-50, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25993607

RESUMEN

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.


Asunto(s)
Trastornos de Ansiedad/genética , Moléculas de Adhesión Celular Neuronal/genética , Trastorno Depresivo Mayor/genética , Personalidad/genética , Proteínas Adaptadoras Transductoras de Señales , Trastornos de Ansiedad/psicología , Moléculas de Adhesión Celular , Trastorno Depresivo Mayor/psicología , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Guanilato-Quinasas , Humanos , Herencia Multifactorial , Neuroticismo , Polimorfismo de Nucleótido Simple , Factores de Riesgo
17.
Eur J Hum Genet ; 23(9): 1223-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25424715

RESUMEN

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.


Asunto(s)
Alanina Transaminasa/genética , Aspartato Aminotransferasas/genética , Patrón de Herencia , Hígado/enzimología , Polimorfismo de Nucleótido Simple , gamma-Glutamiltransferasa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Femenino , Genoma Humano , Estudio de Asociación del Genoma Completo , Humanos , Hígado/química , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Fenotipo , gamma-Glutamiltransferasa/metabolismo
18.
Behav Genet ; 44(4): 295-313, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24828478

RESUMEN

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.


Asunto(s)
Modelos Estadísticos , Determinación de la Personalidad , Personalidad/genética , Trastornos de Ansiedad/genética , Extraversión Psicológica , Estudio de Asociación del Genoma Completo , Humanos , Neuroticismo , Fenotipo
19.
Biomed Res Int ; 2014: 591717, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24734235

RESUMEN

PURPOSE: Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680) and three variable number of tandem repeats (VNTRs in DRD4, upstream of DRD5, and in DAT1) were investigated for an association with regular leisure time exercise behavior. MATERIALS AND METHODS: Data on exercise activities and at least one SNP/VNTR were available for 8,768 individuals aged 7 to 50 years old that were part of the Netherlands Twin Register. Exercise behavior was quantified as weekly metabolic equivalents of task (MET) spent on exercise activities. Mixed models were fitted in SPSS with genetic relatedness as a random effect. RESULTS: None of the genetic variants were associated with exercise behavior (P>.02), despite sufficient power to detect small effects. DISCUSSION AND CONCLUSIONS: We did not confirm that allelic variants involved in dopaminergic function play a role in creating individual differences in exercise behavior. A plea is made for large genome-wide association studies to unravel the genetic pathways that affect this health-enhancing behavior.


Asunto(s)
Alelos , Recompensa , Adolescente , Adulto , Algoritmos , Niño , Simulación por Computador , Dopamina/metabolismo , Ejercicio Físico , Femenino , Variación Genética , Genotipo , Conductas Relacionadas con la Salud , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Países Bajos , Fenotipo , Polimorfismo de Nucleótido Simple , Receptores Dopaminérgicos/genética , Sistema de Registros , Adulto Joven
20.
J Stud Alcohol Drugs ; 75(2): 201-10, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24650813

RESUMEN

OBJECTIVE: The current study aimed to describe what proportion of variation in adult alcohol intake is attributable to genetic differences among individuals and what proportion to differences in environmental experiences individuals have been exposed to. Effects of age, gender, spousal resemblance, and cultural transmission of alcohol intake from parents to offspring were taken into account. METHOD: In a twin-family design, the effects of genetic and cultural transmission and shared and nonshared environment on alcohol intake were estimated with genetic structural equation models. Data originated from adult twins, their siblings, parents (n = 12,587), and spouses (n = 429) registered with the population-based Netherlands Twin Register (63.5% female; ages 18-97 years). RESULTS: Alcohol intake (grams per day) was higher among men than women and increased with age. Broad-sense heritability estimates were similar across sex and age (53%). Spousal resemblance was observed (r = .39) but did not significantly affect the heritability estimates. No effects of cultural transmission were detected. In total, 23% of the variation in alcohol intake was explained by additive genetic effects, 30% by dominant (nonadditive) gene action, and 47% by environmental effects that were not shared among family members. CONCLUSIONS: Individual differences in adult alcohol intake are explained by genetic and individual-specific environmental effects. The same genes are expressed in males and females and in younger and older participants. A substantial part of the heritability of alcohol intake is attributable to nonadditive gene action. Effects of cultural transmission that have been reported in adolescence are not present in adulthood.


Asunto(s)
Consumo de Bebidas Alcohólicas/etnología , Consumo de Bebidas Alcohólicas/genética , Cultura , Individualidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos/etnología , Sistema de Registros , Adulto Joven
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