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1.
Behav Genet ; 49(5): 432-443, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502010

RESUMO

Bullying comes in different forms, yet most previous genetically-sensitive studies have not distinguished between them. Given the serious consequences and the high prevalence of bullying, it is remarkable that the aetiology of bullying and its different forms has been under-researched. We present the first study to investigate the genetic architecture of bullying perpetration, bullying victimization, and their co-occurrence for verbal, physical and relational bullying. Primary-school teachers rated 8215 twin children on bullying perpetration and bullying victimization. For each form of bullying, we investigated, through genetic structural equation modelling, the genetic and environmental influences on being a bully, a victim or both. 34% of the children were involved as bully, victim, or both. The correlation between being a bully and being a victim varied from 0.59 (relational) to 0.85 (physical). Heritability was ~ 70% for perpetration and ~ 65% for victimization, similar in girls and boys, yet both were somewhat lower for the relational form. Shared environmental influences were modest and more pronounced among girls. The correlation between being a bully and being a victim was explained mostly by genetic factors for verbal (~ 71%) and especially physical (~ 77%) and mostly by environmental factors for relational perpetration and victimization (~ 60%). Genes play a large role in explaining which children are at high risk of being a victim, bully, or both. For victimization this suggests an evocative gene-environment correlation: some children are at risk of being exposed to bullying, partly due to genetically influenced traits. So, genetic influences make some children more vulnerable to become a bully, victim or both.

2.
Twin Res Hum Genet ; 22(3): 164-176, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31198125

RESUMO

A literature review was carried out to identify pre and perinatal characteristics associated with variation in Apgar scores in population-based studies. The parameters identified in the literature search were included in the classical twin design study to estimate effects of pre and perinatal factors shared and nonshared by twins and to test for a contribution of genetic factors in 1- and 5-min Apgar scores in a large sample of Dutch monozygotic (MZ) and dizygotic (DZ) twins. The sample included MZ and DZ twins (N = 5181 pairs) recruited by the Netherlands Twin Register shortly after birth, with data on prenatal characteristics and Apgar scores at first and/or fifth minutes. The ordinal regression and structural equation modeling were used to analyze the effects of characteristics identified in the literature review and to estimate genetic and nongenetic variance components. The literature review identified 63 papers. Consistent with the review, we observed statistically significant effects of birth order, zygosity and gestational age (GA) for 1- and 5-min Apgar scores of both twins. Apgar scores are higher in first-born versus second-born twins and DZ first-born versus MZ first-born twins. Birth weight had an effect on the 5-min Apgar of the first born. Fetal presentation and mode of delivery had different effects on Apgar scores of first- and second-born twins. Parental characteristics and chorionicity did not have significant main effects on Apgar scores. The MZ twins' Apgar correlations equaled the DZ Apgar correlations. Our analyses suggest that individual differences in 1- and 5-min Apgar scores are attributable to shared and nonshared pre and perinatal factors, but not to genotypic factors of the newborns. The main predictors of Apgar scores are birth order, zygosity, GA, birth weight, mode of delivery and fetal presentation.

3.
Front Psychiatry ; 9: 261, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962975

RESUMO

Whether well-being and depressive symptoms can be considered as two sides of the same coin is widely debated. The aim of this study was to gain insight into the etiology of the association between well-being and depressive symptoms across the lifespan. In a large twin-design, including data from 43,427 twins between age 7 and 99, we estimated the association between well-being and depressive symptoms throughout the lifespan and assessed genetic and environmental contributions to the observed overlap. For both well-being (range 31-47%) and depressive symptoms (range 49-61%), genetic factors explained a substantial part of the phenotypic variance across the lifespan. Phenotypic correlations between well-being and depressive symptoms across ages ranged from -0.34 in childhood to -0.49 in adulthood. In children, genetic effects explained 49% of the phenotypic correlation while in adolescents and young adults, genetic effects explained 60-77% of the phenotypic correlations. Moderate to high genetic correlations (ranging from -0.59 to -0.66) were observed in adolescence and adulthood, while in childhood environmental correlations were substantial but genetic correlations small. Our results suggest that in childhood genetic and environmental effects are about equally important in explaining the relationship between well-being and depressive symptoms. From adolescence onwards, the role of genetic effects increases compared to environmental effects. These results provided more insights into the etiological underpinnings of well-being and depressive symptoms, possibly allowing to articulate better strategies for health promotion and resource allocation in the future.

4.
Behav Genet ; 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29882082

RESUMO

Although experimental studies are regarded as the method of choice for determining causal influences, these are not always practical or ethical to answer vital questions in health and social research (e.g., one cannot assign individuals to a "childhood trauma condition" in studying the causal effects of childhood trauma on depression). Key to solving such questions are observational studies. Mendelian Randomization (MR) is an influential method to establish causality in observational studies. MR uses genetic variants to test causal relationships between exposures/risk factors and outcomes such as physical or mental health. Yet, individual genetic variants have small effects, and so, when used as instrumental variables, render MR liable to weak instrument bias. Polygenic scores have the advantage of larger effects, but may be characterized by horizontal pleiotropy, which violates a central assumption of MR. We developed the MR-DoC twin model by integrating MR with the Direction of Causation twin model. This model allows us to test pleiotropy directly. We considered the issue of parameter identification, and given identification, we conducted extensive power calculations. MR-DoC allows one to test causal hypotheses and to obtain unbiased estimates of the causal effect given pleiotropic instruments, while controlling for genetic and environmental influences common to the outcome and exposure. Furthermore, the approach allows one to employ strong instrumental variables in the form of polygenic scores, guarding against weak instrument bias, and increasing the power to detect causal effects of exposures on potential outcomes. Beside allowing to test pleiotropy directly, incorporating in MR data collected from relatives provide additional within-family data that resolve additional assumptions like random mating, the absence of the gene-environment interaction/covariance, no dyadic effects. Our approach will enhance and extend MR's range of applications, and increase the value of the large cohorts collected at twin/family registries as they correctly detect causation and estimate effect sizes even in the presence of pleiotropy.

5.
Twin Res Hum Genet ; 21(3): 239-252, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29743129

RESUMO

Twin registers are wonderful research resources for research applications in medical and behavioral genetics, epidemiology, psychology, molecular genetics, and other areas of research. New registers continue to be launched all over the world as researchers from different disciplines recognize the potential to boost and widen their research agenda. In this article, we discuss multiple aspects that need to be taken into account when initiating a register, from its preliminary sketch to its actual development. This encompasses aspects related to the strategic planning and key elements of research designs, promotion and management of a twin register, including recruitment and retaining of twins and family members of twins, phenotyping, database organization, and collaborations between registers. We also present information on questions unique to twin registers and twin-biobanks, such as the assessment of zygosity by SNP arrays, the design of (biomarker) studies involving related participants, and the analyses of clustered data. Altogether, we provide a number of basic guidelines and recommendations for reflection when planning a twin register.

6.
Twin Res Hum Genet ; 21(3): 203-213, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29792248

RESUMO

OBJECTIVE: The human gut microbiota has been demonstrated to be associated with a number of host phenotypes, including obesity and a number of obesity-associated phenotypes. This study is aimed at further understanding and describing the relationship between the gut microbiota and obesity-associated measurements obtained from human participants. SUBJECTS/METHODS: Here, we utilize genetically informative study designs, including a four-corners design (extremes of genetic risk for BMI and of observed BMI; N = 50) and the BMI monozygotic (MZ) discordant twin pair design (N = 30), in order to help delineate the role of host genetics and the gut microbiota in the development of obesity. RESULTS: Our results highlight a negative association between BMI and alpha diversity of the gut microbiota. The low genetic risk/high BMI group of individuals had a lower gut microbiota alpha diversity when compared to the other three groups. Although the difference in alpha diversity between the lean and heavy groups of the BMI-discordant MZ twin design did not achieve significance, this difference was observed to be in the expected direction, with the heavier participants having a lower average alpha diversity. We have also identified nine OTUs observed to be associated with either a leaner or heavier phenotype, with enrichment for OTUs classified to the Ruminococcaceae and Oxalobacteraceae taxonomic families. CONCLUSION: Our study presents evidence of a relationship between BMI and alpha diversity of the gut microbiota. In addition to these findings, a number of OTUs were found to be significantly associated with host BMI. These findings may highlight separate subtypes of obesity, one driven by genetic factors, the other more heavily influenced by environmental factors.

7.
Nat Genet ; 50(5): 668-681, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29700475

RESUMO

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

8.
J Child Psychol Psychiatry ; 59(11): 1205-1214, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29635740

RESUMO

BACKGROUND: This study investigates the causal relationships between reading and print exposure and investigates whether the amount children read outside school determines how well they read, or vice versa. Previous findings from behavioural studies suggest that reading predicts print exposure. Here, we use twin-data and apply the behaviour-genetic approach of direction of causality modelling, suggested by Heath et al. (), to investigate the causal relationships between these two traits. METHOD: Partial data were available for a large sample of twin children (N = 11,559) and 262 siblings, all enrolled in the Netherlands Twin Register. Children were assessed around 7.5 years of age. Mothers completed questionnaires reporting children's time spent on reading activities and reading ability. Additional information on reading ability was available through teacher ratings and performance on national reading tests. For siblings reading test, results were available. RESULTS: The reading ability of the twins was comparable to that of the siblings and national norms, showing that twin findings can be generalized to the population. A measurement model was specified with two latent variables, Reading Ability and Print Exposure, which correlated .41. Heritability analyses showed that Reading Ability was highly heritable, while genetic and environmental influences were equally important for Print Exposure. We exploited the fact that the two constructs differ in genetic architecture and fitted direction of causality models. The results supported a causal relationship running from Reading Ability to Print Exposure. CONCLUSIONS: How much and how well children read are moderately correlated. Individual differences in print exposure are less heritable than individual differences in reading ability. Importantly, the present results suggest that it is the children's reading ability that determines how much they choose to read, rather than vice versa.

9.
Behav Genet ; 48(2): 135-146, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29404830

RESUMO

This study used a theoretically-derived set of items of the Achenbach System of Empirically Based Assessment to develop the Achenbach Self-Control Scale (ASCS) for 7-16 year olds. Using a large dataset of over 20,000 children, who are enrolled in the Netherlands Twin Register, we demonstrated the psychometric properties of the ASCS for parent-, self- and teacher-report by examining internal and criterion validity, and inter-rater and test-retest reliability. We found associations between the ASCS and measures of well-being, educational achievement, and substance use. Next, we applied the classical twin design to estimate the genetic and environmental contributions to self-control. Genetic influences accounted for 64-75% of the variance in self-control based on parent- and teacher-report (age 7-12), and for 47-49% of the variance in self-control based on self-report (age 12-16), with the remaining variance accounted by non-shared environmental influences. In conclusion, we developed a validated and accessible self-control scale, and show that genetic influences explain a majority of the individual differences in self-control across youth aged 7-16 years.


Assuntos
Psicometria/métodos , Autocontrole/psicologia , Gêmeos/psicologia , Adolescente , Fatores Etários , Criança , Feminino , Interação Gene-Ambiente , Humanos , Individualidade , Masculino , Países Baixos , Pais , Inventário de Personalidade , Reprodutibilidade dos Testes , Autorrelato , Gêmeos/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
11.
Behav Genet ; 48(1): 1-11, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29043520

RESUMO

For the participants in the Netherlands Twin Register (NTR) we constructed the extended pedigrees which specify all relations among nuclear and larger twin families in the register. A total of 253,015 subjects from 58,645 families were linked to each other, to the degree that we had information on the relations among participants. We describe the algorithm that was applied to construct the pedigrees. For > 30,000 adolescent and adult NTR participants data were available on harmonized neuroticism scores. We analyzed these data in the Mendel software package (Lange et al., Bioinformatics 29(12):1568-1570, 2013) to estimate the contributions of additive and non-additive genetic factors. In contrast to much of the earlier work based on twin data rather than on extended pedigrees, we could also estimate the contribution of shared household effects in the presence of non-additive genetic factors. The estimated broad-sense heritability of neuroticism was 47%, with almost equal contributions of additive and non-additive (dominance) genetic factors. A shared household effect explained 13% and unique environmental factors explained the remaining 40% of the variance in neuroticism.


Assuntos
Doenças em Gêmeos/genética , Neuroticismo/fisiologia , Gêmeos/genética , Família/psicologia , Feminino , Humanos , Masculino , Modelos Genéticos , Países Baixos/epidemiologia , Linhagem , Sistema de Registros , Meio Social , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
12.
Nicotine Tob Res ; 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29228387

RESUMO

Introduction: The common genetic variant (rs1051730) in the 15q24 nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 was associated with smoking quantity and has been reported to be associated also with reduced ability to quit smoking in pregnant women but results were inconsistent in non pregnant women. The aim of this study was to explore the association between rs1051730 and smoking cessation during pregnancy in a sample of Dutch women. Methods: Data on smoking during pregnancy were available from 1,337 women who ever smoked registered at the Netherlands Twin Register (NTR). Logistic regression was used to assess evidence for association of rs1051730 genotype on smoking during pregnancy. In a subsample of 561 women we investigated the influence of partner's smoking. Educational attainment and year of birth were used as covariates in both analyses. Results: There was evidence for a significant association between having 1 or more T allele's of the rs1051730 polymorphism and the likelihood of smoking during pregnancy (P = 0.03, odds ratio = 1.28, 95% confidence interval: 1.02, 1.61). However, this association attenuated when adjusting for birth cohort and educational attainment (P = 0.37, odds ratio = 1.12, 95% confidence interval: 0.87, 1.43). In the subsample, Smoking spouse was highly associated with smoking during pregnancy, even when educational attainment and birth cohort were included in the model. Conclusions: Our results did not support a strong association between this genetic variant and smoking during pregnancy. However, a strong association was observed with smoking behavior of the partner, regardless of the genotype of the women. Implications: The present study emphasizes the importance of social influences like spousal smoking on smoking behavior of pregnant women. Further research is needed to address the role of rs1051730 genetic variant in influencing smoking cessation and the interaction with important environmental factors like smoking behavior of the partner.

13.
Biol Psychiatry ; 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-29129318

RESUMO

BACKGROUND: The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS × CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample. METHODS: Data were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ∼110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect. RESULTS: MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10-5, R2 = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10-18 and OR = 2.62, p = 1.4 ×10-5 for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66). CONCLUSIONS: No meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT.

14.
Twin Res Hum Genet ; 20(6): 550-557, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29125095

RESUMO

Twin research has offered evidence that monozygotic (MZ) twins are more socially close than dizygotic (DZ) twins, but has not paid much attention to the way twins compare themselves with their co-twin. The few studies in this area suggest that 'horizontal comparisons' (social comparison motivated by solidarity or communion with others) matter more for MZ twins than for DZ twins, at least when the co-twin is the social comparison standard. Consistent with this view, we predicted higher interest in MZ twins relative to DZ twins to select their co-twin rather than other people in general as the social comparison standard. The Social Comparison Orientation (SCO) scale, which measures the inclination to compare with others in a horizontal rather than vertical mode (comparing either upward or downward), was administered in 90 MZ pairs and 57 same-sex DZ pairs (63% female; average age 18.06 years) from the Netherlands Twin Register. MZ twin pairs showed significantly higher SCO scores than DZ twin pairs (with a large effect size) on the co-twin SCO, whereas the two groups did not differ from each other on the general SCO excluding the co-twin as social comparison standard. In MZ twin pairs, anxiety was associated with social comparison with others in general, not with their co-twin. For both scales, twin resemblance was explained by additive genetic variance. The present findings provide direct evidence that horizontal comparisons with the co-twin are of particular importance for MZ twins.


Assuntos
Habilidades Sociais , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto Jovem
15.
Twin Res Hum Genet ; 20(2): 108-118, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28238293

RESUMO

Sequence-based association studies are at a critical inflexion point with the increasing availability of exome-sequencing data. A popular test of association is the sequence kernel association test (SKAT). Weights are embedded within SKAT to reflect the hypothesized contribution of the variants to the trait variance. Because the true weights are generally unknown, and so are subject to misspecification, we examined the efficiency of a data-driven weighting scheme. We propose the use of a set of theoretically defensible weighting schemes, of which, we assume, the one that gives the largest test statistic is likely to capture best the allele frequency-functional effect relationship. We show that the use of alternative weights obviates the need to impose arbitrary frequency thresholds. As both the score test and the likelihood ratio test (LRT) may be used in this context, and may differ in power, we characterize the behavior of both tests. The two tests have equal power, if the weights in the set included weights resembling the correct ones. However, if the weights are badly specified, the LRT shows superior power (due to its robustness to misspecification). With this data-driven weighting procedure the LRT detected significant signal in genes located in regions already confirmed as associated with schizophrenia - the PRRC2A (p = 1.020e-06) and the VARS2 (p = 2.383e-06) - in the Swedish schizophrenia case-control cohort of 11,040 individuals with exome-sequencing data. The score test is currently preferred for its computational efficiency and power. Indeed, assuming correct specification, in some circumstances, the score test is the most powerful test. However, LRT has the advantageous properties of being generally more robust and more powerful under weight misspecification. This is an important result given that, arguably, misspecified models are likely to be the rule rather than the exception in weighting-based approaches.


Assuntos
Interpretação Estatística de Dados , Estudos de Associação Genética/métodos , Modelos Genéticos , Estudos de Casos e Controles , Simulação por Computador , Pesquisa Empírica , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , Variação Genética , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Humanos , Desequilíbrio de Ligação , Masculino , Proteínas/genética , Esquizofrenia/genética , Software , Suécia , Valina-tRNA Ligase/genética
16.
PLoS One ; 12(1): e0170765, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28125671

RESUMO

Telomere length has garnered interest due to the potential role it may play as a biomarker for the cellular aging process. Telomere measurements obtained from blood-derived DNA are often used in epidemiological studies. However, the invasive nature of blood draws severely limits sample collection, particularly with children. Buccal cells are commonly sampled for DNA isolation and thus may present a non-invasive alternative for telomere measurement. Buccal and leukocyte derived DNA obtained from samples collected at the same time period were analyzed for telomere repeat mass (TRM). TRM was measured in buccal-derived DNA samples from individuals for whom previous TRM data from blood samples existed. TRM measurement was performed by qPCR and was normalized to the single copy 36B4 gene relative to a reference DNA sample (K562). Correlations between TRM from blood and buccal DNA were obtained and also between the same blood DNA samples measured in separate laboratories. Using the classical twin design, TRM heritability was estimated (N = 1892, MZ = 1044, DZ = 775). Buccal samples measured for TRM showed a significant correlation with the blood-1 (R = 0.39, p < 0.01) and blood-2 (R = 0.36, p < 0.01) samples. Sex and age effects were observed within the buccal samples as is the norm within blood-derived DNA. The buccal, blood-1, and blood-2 measurements generated heritability estimates of 23.3%, 47.6% and 22.2%, respectively. Buccal derived DNA provides a valid source for the determination of TRM, paving the way for non-invasive projects, such as longitudinal studies in children.


Assuntos
DNA/genética , Leucócitos Mononucleares/metabolismo , Mucosa Bucal/metabolismo , Telômero/química , Adolescente , Adulto , Fatores Etários , Idoso , Criança , DNA/isolamento & purificação , Primers do DNA/química , Feminino , Humanos , Células K562 , Leucócitos Mononucleares/química , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/química , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência , Fatores Sexuais , Irmãos , Gêmeos Dizigóticos , Gêmeos Monozigóticos
17.
Am J Med Genet B Neuropsychiatr Genet ; 174(3): 202-213, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27770494

RESUMO

We review the hypotheses concerning the association between the paternal age at childbearing and childhood psychiatric disorders (autism spectrum- and attention deficit/hyperactive disorder) and adult disorders (schizophrenia, bipolar-, obsessive-compulsive-, and major depressive disorder) based on epidemiological studies. Several hypotheses have been proposed to explain the paternal age effect. We discuss the four main-not mutually exclusive-hypotheses. These are the de novo mutation hypothesis, the hypothesis concerning epigenetic alterations, the selection into late fatherhood hypothesis, and the environmental resource hypothesis. Advanced paternal age in relation to autism spectrum disorders and schizophrenia provided the most robust epidemiological evidence for an association, with some studies reporting a monotonic risk increase over age, and others reporting a marked increase at a given age threshold. Although there is evidence for the de novo mutation hypothesis and the selection into late fatherhood hypothesis, the mechanism(s) underlying the association between advanced paternal age and psychiatric illness in offspring remains to be further clarified. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.


Assuntos
Transtornos Mentais/etiologia , Transtornos do Neurodesenvolvimento/etiologia , Idade Paterna , Fatores Etários , Transtorno do Espectro Autista/genética , Transtorno Bipolar/genética , Transtorno Depressivo Maior/genética , Meio Ambiente , Epigenômica , Feminino , Humanos , Masculino , Idade Materna , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Mutação , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/genética , Fatores de Risco , Esquizofrenia/genética
18.
Dev Psychopathol ; 29(3): 919-928, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27427290

RESUMO

This study sought to identify trajectories of DSM-IV based internalizing (INT) and externalizing (EXT) problem scores across childhood and adolescence and to provide insight into the comorbidity by modeling the co-occurrence of INT and EXT trajectories. INT and EXT were measured repeatedly between age 7 and age 15 years in over 7,000 children and analyzed using growth mixture models. Five trajectories were identified for both INT and EXT, including very low, low, decreasing, and increasing trajectories. In addition, an adolescent onset trajectory was identified for INT and a stable high trajectory was identified for EXT. Multinomial regression showed that similar EXT and INT trajectories were associated. However, the adolescent onset INT trajectory was independent of high EXT trajectories, and persisting EXT was mainly associated with decreasing INT. Sex and early life environmental risk factors predicted EXT and, to a lesser extent, INT trajectories. The association between trajectories indicates the need to consider comorbidity when a child presents with INT or EXT disorders, particularly when symptoms start early. This is less necessary when INT symptoms start at adolescence. Future studies should investigate the etiology of co-occurring INT and EXT and the specific treatment needs of these severely affected children.


Assuntos
Ansiedade/diagnóstico , Desenvolvimento Infantil/fisiologia , Mecanismos de Defesa , Depressão/diagnóstico , Transtornos Mentais/diagnóstico , Adolescente , Ansiedade/psicologia , Criança , Depressão/psicologia , Feminino , Humanos , Masculino , Idade Materna , Transtornos Mentais/psicologia
19.
Biomark Med ; 2016 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-27690543

RESUMO

AIM: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are biomarkers for disease development, for whom little is known about causes of variation in the general population. MATERIALS & METHODS: We estimated the heritability of PLR and NLR and examined their association with gender, demographic, lifestyle and environmental factors in a Dutch nonpatient twin family population (n = 8108). RESULTS: Heritability was estimated at 64% for PLR and 36% for NLR. Men had on average higher NLR, but lower PLR levels than women. PLR and NLR increased significantly with age, decreased in colder months and showed small but significant sex- and age-specific associations with body composition and smoking. CONCLUSION: NLR and PLR levels are heritable and influenced by age, sex and environmental factors, such as seasonal conditions and lifestyle.

20.
Am J Hum Genet ; 99(4): 917-927, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27616482

RESUMO

Here we present a method of genome-wide inferred study (GWIS) that provides an approximation of genome-wide association study (GWAS) summary statistics for a variable that is a function of phenotypes for which GWAS summary statistics, phenotypic means, and covariances are available. A GWIS can be performed regardless of sample overlap between the GWAS of the phenotypes on which the function depends. Because a GWIS provides association estimates and their standard errors for each SNP, a GWIS can form the basis for polygenic risk scoring, LD score regression, Mendelian randomization studies, biological annotation, and other analyses. GWISs can also be used to boost power of a GWAS meta-analysis where cohorts have not measured all constituent phenotypes in the function. We demonstrate the accuracy of a BMI GWIS by performing power simulations and type I error simulations under varying circumstances, and we apply a GWIS by reconstructing a body mass index (BMI) GWAS based on a weight GWAS and a height GWAS. Furthermore, we apply a GWIS to further our understanding of the underlying genetic structure of bipolar disorder and schizophrenia and their relation to educational attainment. Our analyses suggest that the previously reported genetic correlation between schizophrenia and educational attainment is probably induced by the observed genetic correlation between schizophrenia and bipolar disorder and the previously reported genetic correlation between bipolar disorder and educational attainment.


Assuntos
Estudo de Associação Genômica Ampla , Fenótipo , Transtorno Bipolar/genética , Estatura/genética , Índice de Massa Corporal , Peso Corporal/genética , Escolaridade , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Desequilíbrio de Ligação , Masculino , Menarca , Metanálise como Assunto , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Projetos de Pesquisa , Esquizofrenia/genética
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