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1.
Twin Res Hum Genet ; 23(4): 214-220, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32885774

RESUMO

Loneliness is related to mental and somatic health outcomes, including borderline personality disorder. Here, we analyze the sources of variation that are responsible for the relationship between borderline personality features (including four dimensions, affective instability, identity disturbance, negative relationships, self-harm and a total score) and loneliness. Using genetically informative data from two large nonclinical samples of adult twin pairs from Australia and the Netherlands (N = 11,329), we estimate the phenotypic, genetic and environmental correlations between self-reported borderline personality features and loneliness. Individual differences in borderline personality and loneliness were best explained by additive genetic factors with heritability estimates h2 = 41% for the borderline personality total score and h2 = 36% for loneliness, with the remaining variation explained by environmental influences that were not shared by twins from the same pair. Genetic and environmental factors influencing borderline personality (total score and four subscales separately) were also partial causes of loneliness. The correlation between loneliness and the borderline personality total score was rph = .51. The genetic correlation was estimated at rg = .64 and the environmental correlation at re = .40. Our study suggests common etiological factors in loneliness and borderline personality features.

2.
Behav Genet ; 50(5): 363-373, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32419065

RESUMO

The adult self report (ASR) is a well-validated instrument with multiple scales relating to adult psychopathology. Recently, an 18-item version has been introduced, the brief problem monitor (BPM) to measure Internalizing behavior (INT), Externalizing behavior (EXT), and attention problems (ATT). The present study compared the BPM and ASR and investigated how well the BPM can serve as a supplement or an alternative for the ASR for specific clinical and scientific purposes. In a large sample of adult twins (N = 9.835) from the Netherlands Twin Register (NTR), we compared the internal consistency, clinical classification concordance, means, and variances of the ASR and BPM. Using the classical twin design, we investigated the genetic covariance structure. For external validation, the associations between subjective well-being and different subscales of the ASR and BPM were compared. The internal consistency of the BPM scales (around α = 0.75) was somewhat lower than the ASR (α ~ 0.85). The BPM Externalizing scale showed the lowest internal consistency (α = 0.63). ASR and BPM scores showed good clinical classification concordance (0.61-0.80) and high correlations (r > 0.88). A small reversed sex difference in the BPM Externalizing scale appeared (women > men). Genetic (0.34-0.54) and environmental components (0.46-0.66) explained the variance to a similar extent for the ASR and BPM. The phenotypic and genetic associations with well-being were comparable. In situations where sum scores are sufficient, the BPM performs as well as the longer ASR. Depending on the situation and goal, it is worth considering the BPM as an alternative for the ASR to reduce the participant burden.

3.
Biol Psychiatry ; 87(5): 409-418, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635762

RESUMO

BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons. METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses. RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein A1 were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms. CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity.

4.
Twin Res Hum Genet ; 22(6): 623-636, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31666148

RESUMO

The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources - the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping - allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.

5.
Neurology ; 92(16): e1899-e1911, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30944236

RESUMO

OBJECTIVE: To identify a plasma metabolomic biomarker signature for migraine. METHODS: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS: Decreases in the level of apolipoprotein A1 (ß -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (ß -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (ß -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.


Assuntos
Lipoproteínas HDL/metabolismo , Transtornos de Enxaqueca/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Ressonância Magnética Nuclear Biomolecular , Espectroscopia de Prótons por Ressonância Magnética , Fatores Sexuais
6.
Nat Neurosci ; 21(12): 1656-1669, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30482948

RESUMO

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.


Assuntos
Alcoolismo/genética , Predisposição Genética para Doença , Transtornos Mentais/genética , Polimorfismo de Nucleotídeo Único , Alelos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fenótipo
7.
Eur J Hum Genet ; 26(8): 1202-1216, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29995844

RESUMO

Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2 = 12%) and MDD (h2 = 19%), and a significant cross-disorder genetic correlation (rG = 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP ≤ 5 × 10-8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based ≤ 0.05) with both migraine and MDD (Pbinomial-test = 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher's combined gene-based P values that surpassed the genome-wide significance threshold (PFisher's-combined ≤ 3.6 × 10-6). Pathway analysis of genes with PFisher's-combined ≤ 1 × 10-3 suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.


Assuntos
Transtorno Depressivo Maior/genética , Desequilíbrio de Ligação , Transtornos de Enxaqueca/genética , Repetição de Anquirina/genética , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Canais de Potássio de Domínios Poros em Tandem/genética
8.
Blood ; 132(17): 1842-1850, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30042098

RESUMO

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry-specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Metilação de DNA , Hemostasia/fisiologia , Epigênese Genética/fisiologia , Humanos
9.
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.

10.
J Oral Facial Pain Headache ; 32(2): 107­112, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29509827

RESUMO

AIMS: (1) To examine the heritability of TMD pain and of neck pain; and (2) to estimate the potential overlap in genetic and environmental factors influencing TMD pain and neck pain. METHODS: Data from 2,238 adult female twins who completed a survey on TMD pain and neck pain were analyzed. The total variance of TMD pain and neck pain was decomposed into variance attributable to additive genetic effects and nonshared environmental effects. Bivariate structural equation modeling was applied to estimate trait-specific and genetic effects shared between traits. RESULTS: The prevalence of TMD pain and neck pain was 8.6% and 46.8%, respectively, while 6.7% of the twins reported both TMD pain and neck pain. The phenotypic correlation between TMD pain and neck pain, based on a liability threshold model, was 0.43 (95% confidence interval [CI] 0.34 to 0.51). The heritability for TMD was 0.35 (0.17 to 0.51), and for neck pain was 0.33 (0.23 to 0.43). The genetic correlation between TMD pain and neck pain was 0.64 (0.35 to 1.00), and the environmental correlation was 0.32 (0.14 to 0.48). CONCLUSION: This study shows that variation in TMD pain and neck pain can in part be attributed to genes. The comorbidity between them is partly explained by genes that influence both traits and partly by the same environmental factors.

11.
Twin Res Hum Genet ; 21(2): 112-118, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29582723

RESUMO

Migraine and tension-type headache (TTH) are often viewed as distinct entities and defined as such in the International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria, although there is also empirical evidence to suggest they may be etiologically similar. This study aims to investigate whether migraine and TTH are etiologically related conditions. First, we explored whether migraine and TTH were associated with the same environmental and lifestyle risk factors at the population level. Second, we examined comorbidity of migraine and TTH in a twin design. By comparing the associations in monozygotic (MZ) and dizygotic (DZ) twin pairs, we investigated whether the comorbidity can be explained by genetic factors that influence both conditions. Results indicated that migraine and TTH were largely associated with the same environmental and lifestyle factors, including younger age, female sex, higher body mass index, more depression, stress at home, and less participation in regular exercise, with consistently stronger effects for migraine than for TTH. Migraine in one twin was significantly associated with TTH in the other twin. A stronger cross-trait, cross-twin association in MZ than DZ twins suggested that this comorbidity may also be partly due to shared genetic factors, although the difference in associations was not significant. In conclusion, our findings are consistent with the hypothesis that migraine and TTH have partly shared etiologies. For both treatment and research, it may be advisable not to make a rigid distinction, but to treat migraine and TTH as related conditions.


Assuntos
Estilo de Vida , Transtornos de Enxaqueca , Cefaleia do Tipo Tensional , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/fisiopatologia , Fatores de Risco , Cefaleia do Tipo Tensional/genética , Cefaleia do Tipo Tensional/fisiopatologia
12.
Eur Child Adolesc Psychiatry ; 27(9): 1123-1132, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28638947

RESUMO

Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.


Assuntos
Transtorno da Personalidade Antissocial/genética , Transtorno da Conduta/genética , Doenças em Gêmeos/genética , Exposição Ambiental/efeitos adversos , Adolescente , Adulto , Idoso , Transtorno da Personalidade Antissocial/patologia , Criança , Transtorno da Conduta/patologia , Doenças em Gêmeos/patologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
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
14.
Med Sci Sports Exerc ; 50(4): 700-708, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29135816

RESUMO

PURPOSE: Most candidate gene studies on the neurobiology of voluntary exercise behavior have focused on the dopaminergic signaling pathway and its role in the mesolimbic reward system. We hypothesized that dopaminergic candidate genes may influence exercise behavior through additional effects on executive functioning and that these effects are only detected when the types of exercise activity are taken into account. METHODS: Data on voluntary exercise behavior and at least one single-nucleotide polymorphism/variable number of tandem repeat (VNTR) were available for 12,929 participants of the Netherlands Twin Registry. Exercise activity was classified as externally paced if a high level of executive function skill was required. The total volume of voluntary exercise (minutes per week) as well as the volume specifically spent on externally paced activities were tested for association with nine functional dopaminergic polymorphisms (DRD1: rs265981, DRD2/ANKK1: rs1800497, DRD3: rs6280, DRD4: VNTR 48 bp, DRD5: VNTR 130-166 bp, DBH: rs2519152, DAT1: VNTR 40 bp, COMT: rs4680, MAOA: VNTR 30 bp), a polygenic score (PGS) based on nine alleles leading to lower dopamine responsiveness, and a PGS based on three alleles associated with both higher reward sensitivity and better executive functioning (DRD2/ANKK1: "G" allele, COMT: Met allele, DAT1: 440-bp allele). RESULTS: No association with total exercise volume or externally paced exercise volume was found for individual alleles or the nine-allele PGS. The volume of externally paced exercise behavior was significantly associated with the reward and executive function congruent PGS. This association was driven by the DAT1 440-bp and COMT Met allele, which acted as increaser alleles for externally paced exercise behavior. CONCLUSIONS: Taking into account the types of exercise activity may increase the success of identifying genetic variants and unraveling the neurobiology of voluntary exercise behavior.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Exercício Físico , Receptores Dopaminérgicos/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Dopamina/fisiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Herança Multifatorial , Países Baixos , Fenótipo , Polimorfismo de Nucleotídeo Único , Recompensa , Adulto Jovem
15.
Drug Alcohol Depend ; 183: 7-12, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29220643

RESUMO

BACKGROUND: Genetic and environmental factors contribute about equally to alcohol-related phenotypes in adulthood. In the present study, we examined whether more stress at home or low satisfaction with life might be associated with heavier drinking or more alcohol-related problems in individuals with a high genetic susceptibility to alcohol use. METHODS: Information on polygenic scores and drinking behavior was available in 6705 adults (65% female; 18-83 years) registered with the Netherlands Twin Register. Polygenic risk scores (PRSs) were constructed for all subjects based on the summary statistics of a large genome-wide association meta-analysis on alcohol consumption (grams per day). Outcome measures were quantity of alcohol consumption and alcohol-related problems assessed with the Alcohol Use Disorders Identification Test (AUDIT). Stress at home and life satisfaction were moderating variables whose significance was tested by Generalized Estimating Equation analyses taking familial relatedness, age and sex into account. RESULTS: PRSs for alcohol were significantly associated with quantity of alcohol consumption and alcohol-related problems in the past year (R2=0.11% and 0.10% respectively). Participants who reported to have experienced more stress in the past year and lower life satisfaction, scored higher on alcohol-related problems (R2=0.27% and 0.29 respectively), but not on alcohol consumption. Stress and life satisfaction did not moderate the association between PRSs and the alcohol outcome measures. CONCLUSIONS: There were significant main effects of polygenic scores and of stress and life satisfaction on drinking behavior, but there was no support for PRS-by-stress or PRS-by-life satisfaction interactions on alcohol consumption and alcohol-related problems.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Herança Multifatorial/genética , Satisfação Pessoal , Estresse Psicológico/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/complicações , Feminino , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Fatores de Risco , Estresse Psicológico/complicações , Adulto Jovem
16.
Twin Res Hum Genet ; 20(4): 267-270, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28540843

RESUMO

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10-8) and gene-based (p = 1.48 × 10-7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.


Assuntos
Proteínas do Citoesqueleto/genética , Transtorno Depressivo Maior/genética , Neuropeptídeos/genética , Polimorfismo de Nucleotídeo Único , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino
17.
Eur J Oral Sci ; 125(3): 195-201, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28421630

RESUMO

There is limited empirical information as to whether or how stimuli associated with dental fear can be classified into distinct subtypes. The purpose of the current study was to develop a descriptive framework for the classification of dental fear. Data were collected using a survey among Dutch twin families (n = 11,771). The sample was randomly divided into two subsamples of, respectively, 5,920 and 5,851 individuals. An exploratory factor analysis (EFA) was performed on the first subsample to delineate the multidimensional structure of a set of 28 dental-fear-provoking objects and situations. The second sample was used to confirm the newly derived model using confirmatory factor analysis (CFA). The EFA yielded a three-factor solution with 70.7% explained variance pertaining to: (i) invasive treatment or pain; (ii) losing control; and (iii) physical sensations. The CFA showed an acceptable fit to the data, thereby confirming the stability of the three-factor structure. There are at least three different subtypes of dental fear. As these subtypes require a different treatment approach in clinical practice, it could be important to assess the severity of patients' fear response along these three dimensions.


Assuntos
Ansiedade ao Tratamento Odontológico/classificação , Adulto , Ansiedade ao Tratamento Odontológico/etiologia , Ansiedade ao Tratamento Odontológico/psicologia , Análise Fatorial , Medo/psicologia , Feminino , Humanos , Masculino , Modelos Teóricos , Inquéritos e Questionários
18.
Schizophr Bull ; 43(6): 1197-1207, 2017 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-28338919

RESUMO

Background: Several nonpsychotic psychiatric disorders in childhood and adolescence can precede the onset of schizophrenia, but the etiology of this relationship remains unclear. We investigated to what extent the association between schizophrenia and psychiatric disorders in childhood is explained by correlated genetic risk factors. Methods: Polygenic risk scores (PRS), reflecting an individual's genetic risk for schizophrenia, were constructed for 2588 children from the Netherlands Twin Register (NTR) and 6127 from the Avon Longitudinal Study of Parents And Children (ALSPAC). The associations between schizophrenia PRS and measures of anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder/conduct disorder (ODD/CD) were estimated at age 7, 10, 12/13, and 15 years in the 2 cohorts. Results were then meta-analyzed, and a meta-regression analysis was performed to test differences in effects sizes over, age and disorders. Results: Schizophrenia PRS were associated with childhood and adolescent psychopathology. Meta-regression analysis showed differences in the associations over disorders, with the strongest association with childhood and adolescent depression and a weaker association for ODD/CD at age 7. The associations increased with age and this increase was steepest for ADHD and ODD/CD. Genetic correlations varied between 0.10 and 0.25. Conclusion: By optimally using longitudinal data across diagnoses in a multivariate meta-analysis this study sheds light on the development of childhood disorders into severe adult psychiatric disorders. The results are consistent with a common genetic etiology of schizophrenia and developmental psychopathology as well as with a stronger shared genetic etiology between schizophrenia and adolescent onset psychopathology.


Assuntos
Transtornos de Ansiedade , Transtorno do Deficit de Atenção com Hiperatividade , Transtorno da Conduta , Transtorno Depressivo , Herança Multifatorial , Sistema de Registros , Medição de Risco , Esquizofrenia , Adolescente , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/genética , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/etiologia , Transtorno da Conduta/genética , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Transtorno Depressivo/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Países Baixos , Esquizofrenia/epidemiologia , Esquizofrenia/etiologia , Esquizofrenia/genética , Reino Unido
20.
Int J Public Health ; 62(8): 911-919, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28220234

RESUMO

OBJECTIVES: The current study aimed to define the prevalence of dieting and fear of weight gain among men and women across the entire lifespan and identify factors associated with them. METHODS: Data were available for 31,636 participants (60.2% women; age 13-98 years) from the Netherlands Twin Register. Dieting and fear of weight gain were described by age and sex. Associations with BMI, exercise behavior, urbanization and educational attainment were examined by regression analyses in 19,294 participants. RESULTS: Dieting was most frequently reported by 35- to 65-year-old women (56.6-63%), and 45- to 65-year-old men (31.7-31.9%). Fear of weight gain was most prevalent in women between 16 and 25 (73.2-74.3%), and in 25- to 55-year-old men (43.2-46.1%). In addition to sex and BMI, dieting and fear of weight gain were associated with each other. Furthermore, fear was associated with the age × sex interaction and educational attainment. CONCLUSIONS: Dieting and fear of weight gain is common during the entire lifespan for women, but is also endorsed by a substantial number of men. Given the low rate of overweight in young women, the high levels of fear of weight gain are striking.


Assuntos
Dieta Redutora/estatística & dados numéricos , Medo , Ganho de Peso , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Prevalência , Distribuição por Sexo , Adulto Jovem
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