RESUMO
BACKGROUND: Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. METHOD: In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. RESULTS: Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. CONCLUSIONS: Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.
Assuntos
Predisposição Genética para Doença , Núcleo Familiar , Sistema de Registros , Transtornos de Tique/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Linhagem , Transtornos de Tique/epidemiologia , Adulto JovemRESUMO
We examined the longitudinal genetic architecture of three parameters of functional brain connectivity. One parameter described overall connectivity (synchronization likelihood, SL). The two others were derived from graph theory and described local (clustering coefficient, CC) and global (average path length, L) aspects of connectivity. We measured resting state EEG in 1,438 subjects from four age groups of about 16, 18, 25 and 50 years. Developmental curves for SL and L indicate that connectivity is more random at adolescence and old age, and more structured in middle-aged adulthood. Individual variation in SL and L were moderately to highly heritable at each age (SL: 40-82%; L: 29-63%). Genetic factors underlying these phenotypes overlapped. CC was also heritable (25-49%) but showed no systematic overlap with SL and L. SL, CC, and L in the alpha band showed high phenotypic and genetic stability from 16 to 25 years. Heritability for parameters in the beta band was lower, and less stable across ages, but genetic stability was high. We conclude that the connectivity parameters SL, CC, and L in the alpha band show the hallmarks of a good endophenotype for behavior and developmental disorders.
Assuntos
Encéfalo/patologia , Adolescente , Adulto , Comportamento , Mapeamento Encefálico/métodos , Análise por Conglomerados , Deficiências do Desenvolvimento/genética , Eletroencefalografia/métodos , Genótipo , Humanos , Pessoa de Meia-Idade , Modelos Genéticos , Fenótipo , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
Recent studies suggest that individuals with dyslexia may be impaired in probability learning and performance monitoring. These observations are consistent with findings indicating atypical neural activations in frontostriatal circuits in the brain, which are important for associative learning. The current study further examined probability learning and performance monitoring in adult individuals with dyslexia (n = 23) and typical readers (n = 31) using two varieties of a typical probabilistic learning task. In addition to performance measures, we measured heart rate, focusing on cardiac slowing with negative feedback as a manifestation of the automatic performance monitoring system. One task required participants to learn associations between artificial script and speech sounds and the other task required them to learn associations between geometric forms and bird sounds. Corrective feedback (informative or random) was provided in both tasks. Performance results indicated that individuals with dyslexia and typical readers learned the associations equally well in contrast to expectations. We found the typical cardiac response associated with feedback processing consisting of a heart rate slowing with the presentation of the feedback and a return to baseline thereafter. Interestingly, the heart rate slowing associated with feedback was less pronounced and the return to baseline was delayed in individuals with dyslexia relative to typical readers. These findings were interpreted in relation to current theorizing of performance monitoring linking the salience network in the brain to autonomic functioning.
Assuntos
Aprendizagem por Associação/fisiologia , Córtex Cerebral/fisiologia , Disfunção Cognitiva/fisiopatologia , Dislexia/fisiopatologia , Retroalimentação Psicológica/fisiologia , Frequência Cardíaca/fisiologia , Aprendizagem por Probabilidade , Desempenho Psicomotor/fisiologia , Adulto , Disfunção Cognitiva/etiologia , Dislexia/complicações , Eletrocardiografia , Eletroencefalografia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Frontal asymmetry of EEG alpha power (FA) may index the risk for anxiety and depression. Evidence linking FA to the underlying biological mechanisms is scarce. This is unfortunate because FA has potential as a biological marker to support gene finding in anxiety and depression. We examined the heritability of FA in 732 twins and their singleton siblings, and established the genetic and environmental contribution to the relation between FA and the risk for anxiety and depression. Multivariate models showed that FA is heritable only in young adults (males 32% and females 37%) but not in middle-aged adults. A significant relation between FA and the risk for anxiety and depression was only found in young adult females. This relation was explained by shared genes influencing both EEG and disease risk. Future studies on asymmetry of left and right frontal brain activation should carefully consider the effects of sex and age.
Assuntos
Transtornos de Ansiedade/fisiopatologia , Transtorno Depressivo/fisiopatologia , Eletroencefalografia , Lobo Frontal/anatomia & histologia , Lobo Frontal/fisiopatologia , Lateralidade Funcional/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Fenótipo , Fatores de Risco , Inquéritos e Questionários , Gêmeos/fisiologiaRESUMO
Previous studies have reported that individual variation in N1 amplitude is related to attentional problems and alcoholism. Using data from 651 twins and siblings from 292 families we examined whether variation in N1 amplitude and latency can be explained by genetic factors. In half of the subjects the age centered around 26 (young adult cohort), in the other half the age centered around 49 (middle-aged adult cohort). Two visual N1 components were identified by a spatial PCA -- an early anterior component peaking from 88 to 168 ms after stimulus presentation and a posterior one peaking from 132 to 220 ms. Significant heritability was found for anterior N1 amplitude (22%) and posterior amplitude (50%), and for anterior latency (45%) and posterior latency (43%). We conclude that visual N1 amplitude and latency may serve as endophenotypes to detect genetic variation in susceptibility to psychiatric disorders.
Assuntos
Mapeamento Encefálico , Eletroencefalografia , Potenciais Evocados Visuais/genética , Lobo Parietal/fisiologia , Tempo de Reação/genética , Adulto , Fatores Etários , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/anatomia & histologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Fatores Sexuais , Estudos em Gêmeos como Assunto , Percepção Visual/genéticaRESUMO
Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used to identify the co-twin among a larger sample and determined the overlap in functional fingerprints within monozygotic (MZ) twin pairs using resting state magnetoencephalography (MEG). We included 32 cognitively normal MZ twin pairs from the Netherlands Twin Register who participate in the EMIF-AD preclinAD study (average age 68 years). Combining EC information across multiple frequency bands we obtained an identification rate over 75%. Since MZ twin pairs are genetically identical these results suggest a high genetic contribution to MEG-based EC patterns, leading to large similarities in brain connectivity patterns between two individuals even after 60 years of life or more.
Assuntos
Encéfalo/fisiologia , Conectoma , Magnetoencefalografia , Gêmeos Monozigóticos , Feminino , Humanos , Masculino , Países BaixosRESUMO
Variation in obsessive-compulsive symptoms (OCS) has a heritable basis, with genetic association studies starting to yield the first suggestive findings. We contribute to insights into the genetic basis of OCS by performing an extensive series of genetic analyses in a homogeneous, population-based sample from the Netherlands. First, phenotypic and genetic longitudinal correlations over a 6-year period were estimated by modeling OCS data from twins and siblings. Second, polygenic risk scores (PRS) for 6931 subjects with genotype and OCS data were calculated based on meta-analysis results from IOCDF-GC, to investigate their predictive value. Third, the contribution of measured single nucleotide polymorphisms (SNPs) to the heritability was estimated using random-effects modeling. Last, we performed an exploratory genome-wide association study (GWAS) of OCS, testing for SNP- and for gene-based associations. Stability in OCS (test-retest correlation 0.63) was mainly explained by genetic stability. The PRS based on clinical samples predicted OCS in our population-based twin-family sample. SNP-based heritability was estimated at 14%. GWAS revealed one SNP (rs8100480), located within the MEF2BNB gene, associated with OCS (P=2.56 × 10(-8)). Additional gene-based testing resulted in four significantly associated genes, which are located in the same chromosomal region on chromosome 19p13.11: MEF2BNB, RFXANK, MEF2BNB-MEF2B and MEF2B. Thus, common genetic variants explained a significant proportion of OCS trait variation. Genes significantly associated with OCS are expressed in the brain and involved in development and control of immune system functions (RFXANK) and regulation of gene expression of muscle-specific genes (MEF2BNB). MEF2BNB also showed a suggestive association with OCD in an independent case-control study, suggesting a role for this gene in the development of OCS.
Assuntos
Herança Multifatorial/genética , Transtorno Obsessivo-Compulsivo/genética , Polimorfismo de Nucleotídeo Único/genética , Gêmeos/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Países BaixosRESUMO
We estimated the genetic and nongenetic (environmental) contributions to individual differences in the background EEG power spectrum in two age cohorts with mean ages of 26.2 and 49.4 years. Nineteen-lead EEG was recorded with eyes closed from 142 monozygotic and 167 dizygotic twin pairs and their siblings, totaling 760 subjects. We obtained power spectra in 24 bins of 1 Hz ranging from 1.0 to 25.0 Hz. Generally, heritability was highest around the alpha peak frequency and lower in the theta and delta bands. In the beta band heritability gradually decreased with increasing frequency, especially in the temporal regions. Genetic correlations between power in the classical broad bands indicated that half to three-quarters of the genetic variance can be attributed to a common source. We conclude that across the scalp and most of the frequency spectrum, individual differences in adult EEG are largely determined by genetic factors.