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1.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(6): 1089-1094, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369349

RESUMO

Hemispheric asymmetry is a fundamental organizing principle of the human brain. Answering the genetic effects of the asymmetry is a prerequisite for elucidating developmental mechanisms of brain asymmetries. Multi-modal magnetic resonance imaging (MRI) has provided an important tool for comprehensively interpreting human brain asymmetry and its genetic mechanism. By combining MRI data, individual differences in brain structural asymmetry have been investigated with quantitative genetic brain mapping using gene-heritability. Twins provide a useful natural model for studying the effects of genetics and environment on the brain. Studies based on MRI have found that the asymmetry of human brain structure has a genetic basis. From the perspective of quantitative genetic analysis, this article reviews recent findings on the genetic effects of asymmetry and genetic covariance between hemispheres from three aspects: the asymmetry of heritability, the heritability of asymmetry and the genetic correlation. At last, the article shows the limitations and future research directions in this field. The purpose of this systematic review is to quickly guide researchers to understand the origins and genetic mechanism of interhemispheric differences, and provide a genetic basis for further understanding and exploring individual differences in laterized cognitive behavior.


Assuntos
Encéfalo , Imagem por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Gêmeos/genética
2.
Med Sci (Paris) ; 36(8-9): 813-816, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32821057

RESUMO

The prediction of a person's aspect from analysis of an anonymous DNA sample has made significant progress in the last decade. Pigmentation (eyes, hair and, more recently, skin colour) can now be determined with good accuracy; face shape is still not amenable to prediction (except, in general lines, from ancestry). Age can apparently also be determined from methylation profiles. Police forces are, understandably, very interested in this technology, with a tendency to over-estimate its accuracy. Legislation varies greatly, with some nations opting for complete prohibition (Germany) and others allowing wide application of the approach (United Kingdom).


Assuntos
Genética Forense/tendências , Fenótipo , Adulto , Grupos Étnicos/genética , Genética Forense/métodos , Estudos de Associação Genética , Humanos , Recém-Nascido , Padrões de Herança/genética , Masculino , Polimorfismo de Nucleotídeo Único , Retratos como Assunto , Pigmentação da Pele/genética , Gêmeos/genética
3.
Am J Clin Nutr ; 112(4): 956-966, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32685959

RESUMO

BACKGROUND: Obesity susceptibility genes are highly expressed in the brain suggesting that they might exert their influence on body weight through eating-related behaviors. OBJECTIVES: To examine whether the genetic susceptibility to obesity is mediated by eating behavior patterns. METHODS: Participants were 3977 twins (33% monozygotic, 56% females), aged 31-37 y, from wave 5 of the FinnTwin16 study. They self-reported their height and weight, eating behaviors (15 items), diet quality, and self-measured their waist circumference (WC). For 1055 twins with genome-wide data, we constructed a polygenic risk score for BMI (PRSBMI) using almost 1 million single nucleotide polymorphisms. We used principal component analyses to identify eating behavior patterns, twin modeling to decompose correlations into genetic and environmental components, and structural equation modeling to test mediation models between the PRSBMI, eating behavior patterns, and obesity measures. RESULTS: We identified 4 moderately heritable (h2 = 36-48%) eating behavior patterns labeled "snacking," "infrequent and unhealthy eating," "avoidant eating," and "emotional and external eating." The highest phenotypic correlation with obesity measures was found for the snacking behavior pattern (r = 0.35 for BMI and r = 0.32 for WC; P < 0.001 for both), largely due to genetic factors in common (bivariate h2 > 70%). The snacking behavior pattern partially mediated the association between the PRSBMI and obesity measures (ßindirect = 0.06; 95% CI: 0.02, 0.09; P = 0.002 for BMI; and ßindirect = 0.05; 95% CI: 0.02, 0.08; P = 0.003 for WC). CONCLUSIONS: Eating behavior patterns share a common genetic liability with obesity measures and are moderately heritable. Genetic susceptibility to obesity can be partly mediated by an eating pattern characterized by frequent snacking. Obesity prevention efforts might therefore benefit from focusing on eating behavior change, particularly in genetically susceptible individuals.


Assuntos
Comportamento Alimentar , Predisposição Genética para Doença , Obesidade/genética , Gêmeos/genética , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/etiologia , Lanches
5.
BMC Psychol ; 8(1): 37, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321583

RESUMO

BACKGROUND: Left-handedness prevalence has been consistently reported at around 10% with heritability estimates at around 25%. Higher left-handedness prevalence has been reported in males and in twins. Lower prevalence has been reported in Asia, but it remains unclear whether this is due to biological or cultural factors. Most studies are based on samples with European ethnicities and using the preferred hand for writing as key assessment. Here, we investigated handedness in a sample of Chinese school children in Hong Kong, including 426 singletons and 205 pairs of twins, using both the Edinburgh Handedness Inventory and Pegboard Task. RESULTS: Based on a binary definition of writing hand, we found a higher prevalence of left-handedness (8%) than what was previously reported in Asian datasets. We found no evidence of increased left-handedness in twins, but our results were in line with previous findings showing that males have a higher tendency to be left-handed than females. Heritability was similar for both hand preference (21%) and laterality indexes (22%). However, these two handedness measures present only a moderate correlation (.42) and appear to be underpinned by different genetic factors. CONCLUSION: In summary, we report new reference data for an ethnic group usually underrepresented in the literature. Our heritability analysis supports the idea that different measures will capture different components of handedness and, as a consequence, datasets assessed with heterogeneous criteria are not easily combined or compared.


Assuntos
Lateralidade Funcional/genética , Gêmeos/genética , Grupo com Ancestrais do Continente Asiático , Criança , Grupo com Ancestrais do Continente Europeu , Feminino , Hong Kong , Humanos , Padrões de Herança , Masculino , Prevalência , Redação
6.
Proc Natl Acad Sci U S A ; 117(19): 10218-10224, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32341163

RESUMO

People evaluate a stranger's trustworthiness from their facial features in a fraction of a second, despite common advice "not to judge a book by its cover." Evaluations of trustworthiness have critical and widespread social impact, predicting financial lending, mate selection, and even criminal justice outcomes. Consequently, understanding how people perceive trustworthiness from faces has been a major focus of scientific inquiry, and detailed models explain how consensus impressions of trustworthiness are driven by facial attributes. However, facial impression models do not consider variation between observers. Here, we develop a sensitive test of trustworthiness evaluation and use it to document substantial, stable individual differences in trustworthiness impressions. Via a twin study, we show that these individual differences are largely shaped by variation in personal experience, rather than genes or shared environments. Finally, using multivariate twin modeling, we show that variation in trustworthiness evaluation is specific, dissociating from other key facial evaluations of dominance and attractiveness. Our finding that variation in facial trustworthiness evaluation is driven mostly by personal experience represents a rare example of a core social perceptual capacity being predominantly shaped by a person's unique environment. Notably, it stands in sharp contrast to variation in facial recognition ability, which is driven mostly by genes. Our study provides insights into the development of the social brain, offers a different perspective on disagreement in trust in wider society, and motivates new research into the origins and potential malleability of face evaluation, a critical aspect of human social cognition.


Assuntos
Meio Ambiente , Expressão Facial , Reconhecimento Facial/fisiologia , Individualidade , Confiança/psicologia , Gêmeos/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Julgamento , Masculino , Pessoa de Meia-Idade , Resolução de Problemas , Percepção Social , Adulto Jovem
7.
Depress Anxiety ; 37(6): 532-539, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32108979

RESUMO

BACKGROUND: Great variability exists in response to stressful or traumatic events, leading to an interest in the construct of resilience as a trait and an outcome. The etiologic sources of variability across differing conceptualizations of resilience are poorly understood. METHODS: Using behavioral genetic methods in a sample of 2,056 female twins, the present study sought to (a) examine the etiologic sources of a trait-based self-report measure of perceived resilience (PR), (b) determine the genetic and environmental overlap with an outcome-based measure of resilience, as defined by the absence of psychiatric symptoms after stressful life events, previously used by our research team (discrepancy-based psychiatric resilience [DBPR]), and (c) determine the etiologic overlap of these two resilience measures with major depressive disorder (MDD). RESULTS: PR was modestly (11%) heritable. A moderate degree of genetic overlap (39%) and a nominal amount of environmental overlap (3%) were found between the two alternative measures of resilience. Genetic factors that influence PR accounted for 3% of MDD heritability, whereas 31% of MDD heritability was due to DBPR genetic factors. CONCLUSIONS: Findings of a higher genetic correlation between the outcome-based resilience measure and MDD compared to the trait-based measure and MDD suggest gene-finding efforts may benefit from considering the multifaceted nature of resilience and that resilience is best understood as both a phenotypically and genetically heterogeneous construct.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Maior/genética , Doenças em Gêmeos , Feminino , Genética Comportamental , Humanos , Gêmeos/genética
8.
Behav Genet ; 50(2): 94-104, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31975219

RESUMO

We investigated the familial clustering of different classes of voluntary regular exercise behavior in extended twin-family pedigrees. In contrast to the earlier work based on twin data only, this allowed us to estimate the contributions of shared household effects (C), additive (A), and non-additive (D) genetic effects on voluntary exercise behavior. To test whether shared household effects were inflated by assortative mating we examined the causes of spousal resemblance. For adolescent and adult participants (aged 16 to 65) in the Netherlands Twin Register we constructed 19,543 pedigrees which specified all relations among nuclear family members and larger families in the register (N = 50,690 individuals). Data were available on total weekly MET minutes spent on leisure time exercise, and on total weekly MET minutes spent on exercise activities in team-based, solitary, competitive, non-competitive, externally paced and internally paced exercise. We analyzed the data in the Mendel software package (Lange et al. in Bioinformatics 29(12):1568-1570, 2013) under multiple definitions of household sharing and used data from spouses of twins to test phenotypic assortment, social homogamy, and marital interaction as potential sources of spousal resemblance. Results confirmed the influence of genetic factors on the total volume of weekly exercise behavior throughout the life span. Broad sense heritability ranged from 34 to 41% (19-26% A, 12-21% D), and did not depend on the definition for household sharing. Engaging in team-based, competitive, externally paced activities (e.g., soccer) was ~ 13% more heritable than engaging in non-competitive, solitary activities (e.g., jogging). Having shared a household as siblings explained 4-8% of the variance in adult exercise behavior, whereas sharing a household by spouses yielded higher C estimates (20-24%), as it incorporates spousal resemblance. Spousal resemblance was explained by both social homogamy and marital interaction, with little evidence for phenotypic assortment. We conclude that both the amount of voluntary exercise behavior and the preference for specific classes of exercise activities in adults is explained by additive and non-additive genetic factors and unique environmental influences that include correlated exercise behavior of spouses.


Assuntos
Exercício Físico/psicologia , Aptidão Física/psicologia , Gêmeos/psicologia , Adolescente , Adulto , Criança , Exercício Físico/fisiologia , Família , Feminino , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Países Baixos , Linhagem , Fenótipo , Aptidão Física/fisiologia , Gêmeos/genética , Adulto Jovem
9.
Nat Commun ; 11(1): 39, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911595

RESUMO

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.


Assuntos
Sangue/metabolismo , Estudo de Associação Genômica Ampla , Análise Química do Sangue , Estudos de Coortes , Humanos , Metabolômica , Locos de Características Quantitativas , Gêmeos/genética
10.
J Formos Med Assoc ; 119(1 Pt 1): 12-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30709693

RESUMO

BACKGROUND/PURPOSE: With the evolution of assisted fertility and prenatal diagnostic technology, the prevalence of multi-fetal pregnancy increased, followed by the demand for prenatal intervention if genomic aberration was detected. How to distinguish the affected foetus from the normal co-twin before selective fetal reduction is therefore challenging. OBJECTIVES: We retrospectively reviewed the cases of dichorionic twins at our centre during 2004-2018, where selective fetal reduction was requested because one foetus carried a pathogenic genomic aberration. Five cases were enrolled, including three foetuses with trisomy 21, one foetus with microduplication and one foetus with microdeletion disorders. METHOD: We labelled the affected foetus by prenatal ultrasound and rapid molecular tools. For the twins without discriminating sonographic features (e.g., the same gender and no distinct placentae), interphase fluorescence in situ hybridization, rapid microarray and short tandem repeat markers were applied to identify the affected foetus. RESULTS: Selective fetal reduction was allocated accurately for all individuals. Two cases delivered at term, while two delivered preterm, and one developed fetal loss of the co-twin. CONCLUSION: We proposed a working scheme of integrating imaging and molecular techniques to correctly identify the affected co-twin before selective fetal reduction to ensure the accuracy of the identification.


Assuntos
Aberrações Cromossômicas , Síndrome de Down/diagnóstico , Redução de Gravidez Multifetal/métodos , Gravidez de Gêmeos , Diagnóstico Pré-Natal/métodos , Gêmeos/genética , Adulto , Feminino , Idade Gestacional , Humanos , Hibridização in Situ Fluorescente , Análise em Microsséries , Repetições de Microssatélites , Gravidez , Estudos Retrospectivos , Taiwan , Ultrassonografia Pré-Natal
11.
Eur Child Adolesc Psychiatry ; 29(2): 205-216, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31111269

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. However, no study has examined genetic and environmental influences in the longitudinal developmental course of ADHD symptoms in a non-Western population. This study investigated changes of genetic and environmental influences and their contributions to the stability and change of ADHD symptoms of hyperactivity/impulsivity and inattention in Chinese adolescent twins. A prospective sample of 602 twin pairs (48% male) self-reported both DSM-IV ADHD symptom subscales three times at the approximate age of 12, 13, and 15 years. Longitudinal multivariate genetic analyses through structural equation modelling examined genetic and environmental contributions to the developmental course of ADHD symptoms. From early (time 1 and 2) to middle adolescence (time 3), both symptoms showed modest and non-significant genetic influences that became substantial and significant, whereas shared environmental influences were substantial and significant and became modest and non-significant. The same genetic factors influenced ADHD symptoms throughout adolescence, while shared and non-shared environmental influences largely came from new emerging factors. In early adolescence, genetic factor contributed to the stability of inattention, whereas shared environmental factor contributed to the stability of hyperactivity/impulsivity. Genetic influences of ADHD tended to be smaller, whereas shared environmental influences tended to be larger in Chinese than in Western populations. Genetic factors played a large role in the stability of ADHD throughout adolescence, while shared and non-shared environment primarily contributed to its change. Findings highlight the importance of shared family, neighbourhood, and community experiences on child psychopathology in a collectivistic culture such as the Chinese society.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Gêmeos/genética , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Autorrelato
12.
Int J Eat Disord ; 53(1): 52-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31429983

RESUMO

OBJECTIVE: Despite established comorbidity between anxiety and disordered eating (DE), and a plethora of research using various methodologies to examine this overlap, use of twin modeling to expose whether a shared genetic liability underpins these conditions remains rare. METHOD: Data from a longitudinal sample of female twins were selected: measures of risk for DE from Wave 1 (N = 699, 351 pairs, aged 12-15 years), and the Eating Disorder Examination (EDE) and Children's Anxiety Sensitivity Index (CASI) from Wave 2 (N = 669, 338 pairs, aged 16-19 years). At this time, they also completed Children's Anxiety Sensitivity Index (CASI). Bivariate Cholesky decomposition models adjusting for age and body mass index centile investigated the covariance structure between the CASI and EDE. RESULTS: Modeling both genetic and nonshared environmental influences parsimoniously fit these data. All paths were significant. Additive genetic influences were notable for CASI and EDE phenotypes; 14% of the heritable variance was contributed by CASI to the expression of EDE. There was also a smaller but significant contribution of nonshared environmental influences. A multinomial logistic regression indicated body dissatisfaction (RRR = 1.53; 95% CI = 1.07-2.18) differentiated groups with highest EDE scores from the highest CASI scores. DISCUSSION: Shared genetic and environmental influences appear to underpin the relationship, and potentially the observed comorbidity, between anxiety sensitivity and DE. The age of onset is typically earlier for anxiety than DE, suggesting a significant opportunity for early intervention work to reduce the likelihood of subsequent development of DE.


Assuntos
Ansiedade/genética , Doenças em Gêmeos/genética , Transtornos da Alimentação e da Ingestão de Alimentos/genética , Gêmeos/genética , Adolescente , Ansiedade/psicologia , Criança , Estudos de Coortes , Comorbidade , Exposição Ambiental , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco
13.
Psychiatry Res ; 286: 112548, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31495512

RESUMO

Posttraumatic stress disorder (PTSD) and insomnia are comorbid clinical conditions that are thought to result from genetic and environmental effects. Though studies have established the heritability of these disorders independently, no study to date has examined the genetic contributions to the relation between insomnia and PTSD symptoms (PTSS). The present study assessed this gap in the literature using a behavioral genetics approach to symptom dimensions. The sample consisted of 242 twin pairs who endorsed lifetime trauma exposure. Insomnia symptoms were assessed with the Women's Health Initiative Survey, and intrusion and avoidance PTSS were assessed with the Impact of Events Scale. Structural equation modeling was then employed to test the relative contributions of genetic, shared environmental, and nonshared environmental components to the relations between insomnia symptoms and intrusions and avoidance. Results indicated a significant association between insomnia symptoms and intrusions (r = 0.33, p < 0.01) and insomnia symptoms and avoidance (r = 0.20, p < 0.01), and 36-44% of phenotypic variance was accounted for by genetic contributions. These findings highlight a significant role for genetic factors in the mechanisms underlying the comorbidity between insomnia and PTSS. The implications for current etiological models of PTSD and insomnia are discussed.


Assuntos
Doenças em Gêmeos/etiologia , Doenças em Gêmeos/genética , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/genética , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/genética , Gêmeos/genética , Adulto , Idoso , Comorbidade , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Washington/epidemiologia
14.
J Autism Dev Disord ; 50(6): 2188-2200, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30859356

RESUMO

Visual disengagement has been hypothesized as an endophenotype for autism. In this study we used twin modelling to assess the role of genetics in basic measures of visual disengagement, and tested their putative association to autistic traits in the general population. We used the Gap Overlap task in a sample of 492 twins. Results showed that most of the covariance among eye movement latencies across conditions was shared and primarily genetic. Further, there were unique genetic contributions to the Gap condition, but not to the Overlap condition-i.e. the one theorized to capture visual disengagement. We found no phenotypic association between autistic traits and disengagement, thus not supporting the hypothesis of visual disengagement as an endophenotype for autistic traits.


Assuntos
Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Gêmeos/genética , Criança , Endofenótipos , Movimentos Oculares , Feminino , Humanos , Masculino
15.
Eur Child Adolesc Psychiatry ; 29(3): 353-362, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31154517

RESUMO

Socioeconomic status (SES) affects the development of childhood behavioral problems. It has been frequently observed that children from low SES background tend to show more behavioral problems. There also is some evidence that SES has a moderating effect on the causes of individual differences in childhood behavioral problems, with lower heritability estimates and a stronger contribution of environmental factors in low SES groups. The aim of the present study was to examine whether the genetic architecture of childhood behavioral problems suggests the presence of protective and/or harmful effects across socioeconomic strata, in two countries with different levels of socioeconomic disparity: the Netherlands and the United Kingdom. We analyzed data from 7-year-old twins from the Netherlands Twin Register (N = 24,112 twins) and the Twins Early Development Study (N = 19,644 twins). The results revealed a nonlinear moderation effect of SES on the contribution of genetic and environmental factors to individual differences in childhood behavioral problems. The heritability was higher, the contribution of the shared environment was lower, and the contribution of the nonshared environment was higher, for children from high SES families, compared to children from low or medium SES families. The pattern was similar for Dutch and UK families. We discuss the importance of these findings for prevention and intervention goals.


Assuntos
Transtornos do Comportamento Infantil/genética , Fatores Socioeconômicos , Gêmeos/genética , Criança , Feminino , Humanos , Masculino , Países Baixos , Reino Unido
16.
Blood ; 135(4): 261-268, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31697811

RESUMO

Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is defined by mutations in myeloid cancer-associated genes with a variant allele frequency of at least 2%. Recent studies have suggested a possible genetic predisposition to CH. To further explore this phenomenon, we conducted a population-based study of 594 twins from 299 pairs aged 73 to 94 years, all with >20 years' follow-up. We sequenced DNA from peripheral blood with a customized 21-gene panel at a median coverage of 6179X. The casewise concordance rates for mutations were calculated to assess genetic predisposition. Mutations were identified in 214 (36%) of the twins. Whereas 20 twin pairs had mutations within the same genes, the exact same mutation was only observed in 2 twin pairs. No significant difference in casewise concordance between monozygotic and dizygotic twins was found for any specific gene, subgroup, or CHIP mutations overall, and no significant heritability could be detected. In pairs discordant for CHIP mutations, we tested if the affected twin died before the unaffected twin, as a direct measurement of the association of having CH when controlling for familial factors. A total of 127 twin pairs were discordant for carrying a mutation, and in 61 (48%) cases, the affected twin died first (P = .72). Overall, we did not find a genetic predisposition to CHIP mutations in this twin study. The previously described negative association of CHIP mutations on survival could not be confirmed in a direct comparison among twin pairs that were discordant for CHIP mutations.


Assuntos
Hematopoese , Leucemia Mieloide/genética , Gêmeos/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doenças em Gêmeos/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Humanos , Leucemia Mieloide/mortalidade , Masculino , Mutação , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
17.
Blood ; 135(4): 269-273, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31697828

RESUMO

Although acquisition of leukemia-associated somatic mutations by 1 or more hematopoietic stem cells is inevitable with advancing age, its consequences are highly variable, ranging from clinically silent clonal hematopoiesis (CH) to leukemic progression. To investigate the influence of heritable factors on CH, we performed deep targeted sequencing of blood DNA from 52 monozygotic (MZ) and 27 dizygotic (DZ) twin pairs (aged 70-99 years). Using this highly sensitive approach, we identified CH (variant allele frequency ≥0.5%) in 62% of individuals. We did not observe higher concordance for CH within MZ twin pairs as compared with that within DZ twin pairs, or to that expected by chance. However, we did identify 2 MZ pairs in which both twins harbored identical rare somatic mutations, suggesting a shared cell of origin. Finally, in 3 MZ twin pairs harboring mutations in the same driver genes, serial blood samples taken 4 to 5 years apart showed substantial twin-to-twin variability in clonal trajectories. Our findings propose that the inherited genome does not exert a dominant influence on the behavior of adult CH and provide evidence that CH mutations may be acquired in utero.


Assuntos
Hematopoese , Leucemia/genética , Mutação , Gêmeos/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doenças em Gêmeos/genética , Feminino , Humanos , Masculino , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
18.
Drug Alcohol Depend ; 206: 107712, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753729

RESUMO

BACKGROUND: It is unclear whether cannabis use causes cognitive decline; several studies show an association between cannabis use and cognitive decline, but quasi-experimental twin studies have found little support for a causal effect. Here, we evaluate the association of cannabis use with general cognitive ability and executive functions (EFs) while controlling for genetic and shared environmental confounds in a longitudinal twin study. METHODS: We first examined the phenotypic associations between cannabis initiation, frequency, and use disorder with cognitive abilities, while also controlling for pre-use general cognitive ability and other substance involvement. We tested the concurrent association between the cannabis use variables and cognitive abilities in late adolescence and young adulthood and the longitudinal association between cannabis use variables during adolescence and young adulthood cognitive abilities. Next, we used multilevel models to test whether these relations reflect between- and/or within-twin pair associations. RESULTS: Phenotypically, cannabis use was related to poorer cognitive functioning, although most associations were negligible after accounting for other substance use. Nevertheless, there were few significant within-family twin-specific associations, except that age 17 cannabis frequency was associated with worse age 23 Common EF and general cognitive ability. CONCLUSIONS: We found little support for a potential causal effect of cannabis use on cognition, consistent with previous twin studies. Results suggest that cannabis use may not cause decline in cognitive ability among a normative sample of cannabis users.


Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Uso da Maconha/psicologia , Gêmeos/psicologia , Adolescente , Adulto , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Masculino , Uso da Maconha/genética , Ensaios Clínicos Controlados não Aleatórios como Assunto , Fenótipo , Gêmeos/genética , Adulto Jovem
19.
Behav Genet ; 50(2): 105-118, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31811520

RESUMO

This study documented the etiology contributions between anxiety symptoms (AS) and depressive symptoms (DS) from ages 6-12 years. Teachers assessed AS and DS in 1112 twins at 5 time points. A genetic cross-lagged model was used to estimate genetic/environmental contributions to cross-sectional, cross-age and cross-lag associations. The variance in AS and DS was largely time-specific and more genetic in nature for DS than for AS. Previous DS predicted subsequent DS better than cross-lag or previous common effects, and AS up to age 9 better than previous AS or previous common effects. Thereafter, previous AS predicted subsequent AS. All predictions involved both genetic and unique environment. Suppression effects were found and, when controlled, AS marginally predicted DS from age 7 onward through genetic influences. AS and DS are associated throughout childhood. DS are more stable than AS, and more central to both subsequent AS and DS. AS marginally contribute to subsequent DS.


Assuntos
Ansiedade/genética , Depressão/genética , Gêmeos/psicologia , Ansiedade/etiologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/genética , Criança , Estudos Transversais , Depressão/etiologia , Transtorno Depressivo/etiologia , Transtorno Depressivo/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Modelos Genéticos , Gêmeos/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
20.
Behav Genet ; 50(2): 73-83, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31820295

RESUMO

The Louisville Twin Study (LTS) began in 1958 and became a premier longitudinal twin study of cognitive development. The LTS continuously collected data from twins through 2000 after which the study closed indefinitely due to lack of funding. Now that the majority of the sample is age 40 or older (61.36%, N = 1770), the LTS childhood data can be linked to midlife cognitive functioning, among other physical, biological, social, and psychiatric outcomes. We report results from two pilot studies in anticipation of beginning the midlife phase of the LTS. The first pilot study was a participant tracking study, in which we showed that approximately 90% of the Louisville families randomly sampled (N = 203) for the study could be found. The second pilot study consisted of 40 in-person interviews in which twins completed cognitive, memory, biometric, and functional ability measures. The main purpose of the second study was to correlate midlife measures of cognitive functioning to a measure of biological age, which is an alternative index to chronological age that quantifies age as a function of the breakdown of structural and functional physiological systems, and then to relate both of these measures to twins' cognitive developmental trajectories. Midlife IQ was uncorrelated with biological age (- .01) while better scores on episodic memory more strongly correlated with lower biological age (- .19 to - .31). As expected, midlife IQ positively correlated with IQ measures collected throughout childhood and adolescence. Additionally, positive linear rates of change in FSIQ scores in childhood significantly correlated with biological age (- .68), physical functioning (.71), and functional ability (- .55), suggesting that cognitive development predicts lower biological age, better physical functioning, and better functional ability. In sum, the Louisville twins can be relocated to investigate whether and how early and midlife cognitive and physical health factors contribute to cognitive aging.


Assuntos
Envelhecimento/fisiologia , Envelhecimento Cognitivo/fisiologia , Envelhecimento Cognitivo/psicologia , Cognição/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Gêmeos/genética , Gêmeos/psicologia , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia
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