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1.
Twin Res Hum Genet ; 27(1): 50-55, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38444332

RESUMO

There are sex-dependent differences in hematological and biochemical variables in adulthood attributed to the predominant effects of testosterone in males and estrogen in females. The Twin Testosterone Transfer (TTT) hypothesis proposes that opposite-sex females may develop male-typical traits due to exposure to relatively higher levels of prenatal testosterone than same-sex females. Additionally, prenatal testosterone exposure has been suggested as a correlate of current circulating testosterone levels. Consequently, opposite-sex females might exhibit male-typical patterns in their hematological and biochemical variables. Despite this hypothesis, routine laboratory investigations assign the same reference range to all females. Our cross-sectional study, conducted in Tamale from January to September 2022, included 40 twins, comprising 10 opposite-sex (OS) males (25%), 10 OS females (25%), and 20 same-sex (SS) females (50%), all aged between 18 and 27 years. Fasting venous blood samples were collected and analyzed using automated hematology and biochemistry laboratory analyzers. Results indicated that levels of hemoglobin, serum creatinine, gamma-glutamyl transferase, total protein, globulins, and total testosterone were significantly higher in OS males than OS females. Conversely, total cholesterol and low-density lipoprotein cholesterol were significantly higher in OS females than OS males. Unexpectedly, levels of low-density lipoprotein cholesterol and total testosterone were significantly higher in SS females than OS females. Contrary to expectations, opposite-sex females did not exhibit male-typical patterns in their hematological and biochemical variables. This suggests that the TTT effect may not occur or may not be strong enough to markedly affect hematological and biochemical variables in OS females.


Assuntos
Testosterona , Humanos , Feminino , Masculino , Adulto , Gana/epidemiologia , Testosterona/sangue , Estudos Transversais , Adolescente , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto Jovem
2.
Nat Hum Behav ; 7(6): 849-860, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37188734

RESUMO

In the classical twin design, researchers compare trait resemblance in cohorts of identical and non-identical twins to understand how genetic and environmental factors correlate with resemblance in behaviour and other phenotypes. The twin design is also a valuable tool for studying causality, intergenerational transmission, and gene-environment correlation and interaction. Here we review recent developments in twin studies, recent results from twin studies of new phenotypes and recent insights into twinning. We ask whether the results of existing twin studies are representative of the general population and of global diversity, and we conclude that stronger efforts to increase representativeness are needed. We provide an updated overview of twin concordance and discordance for major diseases and mental disorders, which conveys a crucial message: genetic influences are not as deterministic as many believe. This has important implications for public understanding of genetic risk prediction tools, as the accuracy of genetic predictions can never exceed identical twin concordance rates.


Assuntos
Transtornos Mentais , Gêmeos Dizigóticos , Humanos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Transtornos Mentais/genética , Fatores de Risco , Comportamentos Relacionados com a Saúde
3.
Med Sci Sports Exerc ; 55(10): 1845-1856, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184488

RESUMO

INTRODUCTION: The contribution of genetic and environmental factors to individual differences in early motor development is still largely uncharted. This large-scale twin study establishes the genetic and environmental influences on the timing of motor milestones achievement, and it further tests whether the influences are moderated by parental education. METHODS: The twins came from families registered in the Netherlands Twin Register (NTR) from 1986 to 2016. In 30,256 complete twin pairs, mother-reported ages at which each twin was able to first-time roll from back to belly, sit unassisted, hands-and-knees crawl, stand up unaided, and walk independently were used to extract an early motor development factor. Parental education was dichotomized ("both parents with low/average education" vs "at least one parent with high education" with university degree as a threshold). RESULTS: Additive genetics explained 52% of the variance in motor development, the remaining 39% and 9% were explained by shared and nonshared environment separately. Mean age of achieving motor milestones tended to be higher in infants with high educated parents, and a moderation of parental education on the genetic and environmental variance in motor development was seen in female twins with larger heritability in the high educated parents group (64% vs 43%) paired to a lower shared environmental influence (28% vs 48%). Only 7%-8% of the variance was accounted for nonshared environmental factors, including measurement error. The pattern of results did not change when the degree of urbanicity, a correlate of parental education, was additionally considered. CONCLUSIONS: Genetic factors explain most of the individual differences in the timing of motor milestone achievement, but factors related to the shared home environment also play an important role in early motor development.


Assuntos
Pais , Gêmeos , Feminino , Humanos , Lactente , Escolaridade , Fatores Socioeconômicos , Gêmeos/genética , Gêmeos Monozigóticos/genética , Caminhada
4.
Medicina (Kaunas) ; 58(12)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36557058

RESUMO

Background and Objectives: Our aim was to assess genetic and environmental effects on surface morphological parameters for quantifying anterior cingulate cortex (ACC) changes in middle- to advanced-age East Asians using twin analysis. Materials and Methods: Normal twins over 39 years old comprising 37 monozygotic pairs and 17 dizygotic pairs underwent 3-dimensional (3D) T1-weighted imaging of the brain at 3T. Freesurfer-derived ACC parameters including thickness, standard deviation of thickness (STDthickness), volume, surface area, and sulcal morphological parameters (folding, mean, and Gaussian curvatures) were calculated from 3D T1-weighted volume images. Twin analysis with a model involving phenotype variance components of additive genetic effects (A), common environmental effects (C), and unique environmental effects (E) was performed to assess the magnitude of each genetic and environmental influence on parameters. Results: Most parameters fit best with an AE model. Both thickness (A: left 0.73/right 0.71) and surface area (A: left 0.63/right 0.71) were highly heritable. STDthickness was low to moderately heritable (A: left 0.48/right 0.29). Volume was moderately heritable (A: left 0.37). Folding was low to moderately heritable (A: left 0.44/right 0.28). Mean curvature (A: left 0.37/right 0.65) and Gaussian curvature (A: right 0.79) were moderately to highly heritable. Right volume and left Gaussian curvature fit best with a CE model, indicating a relatively weak contribution of genetic factors to these parameters. Conclusions: When assessing ACC changes in middle- to advanced-age East Asians, one must keep in mind that thickness and surface area appear to be strongly affected by genetic factors, whereas sulcal morphological parameters tend to involve environmental factors.


Assuntos
Encéfalo , Giro do Cíngulo , Giro do Cíngulo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ásia Oriental , Biomarcadores , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
5.
Sci Rep ; 12(1): 13148, 2022 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-35909142

RESUMO

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.


Assuntos
Abandono do Hábito de Fumar , Gêmeos Monozigóticos , Criança , Escolaridade , Humanos , Fumar/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
6.
J Clin Pediatr Dent ; 46(2): 160-170, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35533222

RESUMO

BACKGROUND: The aim of this study is to investigate the relative contributions of genetic and environmental factors to variations in dental dimensions in a sample of Turkish twins, and to estimate heritability using dental casts. STUDY DESIGN: The study samples were selected from the twin children between 3-15 years old who referred for their first dental examination. Fifty nine monozygotic and one hundred and forty three dizygotic twin pairs were examined in the study. The alginate impression material used to create the plaster model of maxilla and mandible. Anterior arch width, posterior arch width, arch length and arch circumference were measured on models prepared from measurements taken for both maxilla and mandible with digital caliper. The similarities and differences of the measurements were compared between pairs of twins and zygocytes. Morever, the effects of bad oral habits, bruxism, a result of psychosocial factors on measurements were examined. Statistical analysis was performed using Paired T Test, Wilcoxon Test and Mann Whitney U test. RESULTS: A total of 404 dental models of 118 (29.2%) monozygotic and 286 (70.8%) dizygotic twins were evaluated. There was no statistical difference between sibling pairs in both monozygotic and dizygotic twins. The measurement similarity between twin siblings differed according to zygosity in all measurements (p<0.05). It has been observed that the finger sucking and mouth breathing affect the dental arch measurements (p<0.05). CONCLUSION: These results indicate that the differences in dental arch dimensions between monozygotic twin pairs are less than the difference between dizygotic twin pairs.


Assuntos
Arco Dental , Gêmeos Dizigóticos , Adolescente , Criança , Pré-Escolar , Humanos , Mandíbula , Maxila , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
7.
J Cosmet Dermatol ; 21(5): 1940-1947, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35201665

RESUMO

BACKGROUND: Facial aging is a complex process, which, beyond a genetic predisposition, involves both physical and environmental factors. Even identical twins with the same genetic load may differ substantially in facial wrinkles and aging, demanding a personalized treatment approach. OBJECTIVE: To demonstrate the ONE21 technique as an excellent tool to a customized assessment and IncobotulinuntoxinA treatment to address phenotype discordances and epigenetic drifts in identical twins, expressed by different patterns of upper face muscle contractions and wrinkles intensity. PATIENTS/METHODS: Five pairs of identical Caucasian twin sisters, from 30 to 45 years of age, were evaluated for hyperfunctional upper facial wrinkles (forehead, glabella, and periorbital), assessing the individual anatomy, muscle function and habitual facial movements of each patient. All the subjects were treated with the ONE21 technique using IncobotulinumtoxinA and reevaluated 30 days after the procedure. RESULTS: Though the clinical-anatomical pattern of the forehead contraction was similar between the pairs, the strength of the muscles, the number and depth of wrinkles differed. This varied presentation demanded distinct points of distribution and dosages of incobotulinumtoxinA for all the twins, according to the ONE21 approach. The results 30 days after treatment were satisfactory in all the subjects. CONCLUSION: The ONE21 technique allows an objective and careful evaluation of the wrinkles of the upper face, based on an individualized assessment, which may vary even in identical twins.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Envelhecimento da Pele , Músculos Faciais , Humanos , Envelhecimento da Pele/genética , Gêmeos Monozigóticos/genética
8.
JAMA Health Forum ; 2(7): e211652, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-35977209

RESUMO

Importance: Wealthy adults tend to live longer than those with less wealth. However, a challenge in this area of research has been the reduction of potential confounding by factors associated with the early environment and heritable traits, which could simultaneously affect socioeconomic circumstances in adulthood and health across the life course. Objective: To identify the association between net worth at midlife and subsequent all-cause mortality in individuals as well as within siblings and twin pairs. Design Setting and Participants: This cohort study conducted a series of analyses using data from the Midlife in the United States (MIDUS) study, an ongoing national study of health and aging. The sample included adults (unrelated individuals, full siblings, and dizygotic and monozygotic twins) aged 20 to 75 years, who participated in wave 1 of the MIDUS study, which occurred from 1994 to 1996. The analyses were conducted between November 16, 2019, and May 18, 2021. Exposures: Self-reported net worth (total financial assets minus liabilities) at midlife (the middle years of life). Main Outcomes and Measures: All-cause mortality was tracked over nearly 24 years of follow-up, with a censor date of October 31, 2018. Survival models tested the association between net worth and all-cause mortality. Discordant sibling and twin analyses compared longevity within siblings and twin pairs who, given their shared early experiences and genetic backgrounds, were matched on these factors. Results: The full sample comprised 5414 participants, who had a mean (SD) age of 46.7 (12.7) years and included 2766 women (51.1%). Higher net worth was associated with lower mortality risk (hazard ratio [HR], 0.95; 95% CI, 0.94-0.97; P < .001). Among siblings and twin pairs specifically (n = 2490), a similar within-family association was observed between higher net worth and lower mortality (HR, 0.94; 95% CI, 0.91-0.97; P = .001), suggesting that the sibling or twin with more wealth tended to live longer than their co-sibling or co-twin with less wealth. When separate estimates were performed for the subsamples of siblings (HR, 0.94; 95% CI, 0.90-0.97; P = .002), dizygotic twins (HR, 0.94; 95% CI, 0.86-1.02; P = .19), and monozygotic twins (HR, 0.95; 95% CI, 0.87-1.04; P = .34), the within-family estimates of the net worth-mortality association were similar, although the precision of estimates was reduced among twins. Conclusions and Relevance: This cohort study found that wealth accumulation at midlife was associated with longevity in US adults. Discordant sibling analyses suggested that this association is unlikely to be simply an artifact of early experiences or heritable characteristics shared by families.


Assuntos
Longevidade , Classe Social , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Longevidade/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Estados Unidos/epidemiologia , Adulto Jovem
9.
Twin Res Hum Genet ; 23(1): 8-15, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31983355

RESUMO

In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide.


Assuntos
Doenças em Gêmeos/genética , Interação Gene-Ambiente , Estudos em Gêmeos como Assunto , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Pesquisa Biomédica/métodos , Doenças em Gêmeos/congênito , Doenças em Gêmeos/embriologia , Epigênese Genética/fisiologia , Feminino , Humanos , Masculino , Microbiota/genética , Sistema de Registros , Células-Tronco/metabolismo , Células-Tronco/patologia
10.
Twin Res Hum Genet ; 22(6): 667-671, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31500683

RESUMO

The Murcia Twin Registry (MTR) is the only population-based registry in Spain. Created in 2006, the registry has been growing more than a decade to become one of the references for twin research in the Mediterranean region. The MTR database currently comprises 3545 adult participants born between 1940 and 1977. It also holds a recently launched satellite registry of university students (N = 204). Along five waves of data collection, the registry has gathered questionnaire and anthropometric data, as well as biological samples. The MTR keeps its main research focus on health and health-related behaviors from a public health perspective. This includes lifestyle, health promotion, quality of life or environmental conditions. Future short-term development points to the expansion of the biobank and the continuation of the collection of longitudinal data.


Assuntos
Pesquisa Biomédica , Doenças em Gêmeos/epidemiologia , Comportamentos Relacionados com a Saúde , Qualidade de Vida , Sistema de Registros/estatística & dados numéricos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Doenças em Gêmeos/genética , Doenças em Gêmeos/psicologia , Feminino , Seguimentos , Promoção da Saúde , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Espanha/epidemiologia , Inquéritos e Questionários
11.
Twin Res Hum Genet ; 22(6): 809-816, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31544729

RESUMO

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene-environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14-103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.


Assuntos
Interação Gene-Ambiente , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Seguimentos , Humanos , Pessoa de Meia-Idade
12.
Proc Natl Acad Sci U S A ; 116(36): 17741-17746, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31431527

RESUMO

A foundational question in the social sciences concerns the interplay of underlying causes in the formation of people's political beliefs and prejudices. What role, if any, do genes, environmental influences, or personality dispositions play? Social dominance orientation (SDO), an influential index of people's general attitudes toward intergroup hierarchy, correlates robustly with political beliefs. SDO consists of the subdimensions SDO-dominance (SDO-D), which is the desire people have for some groups to be actively oppressed by others, and SDO-egalitarianism (SDO-E), a preference for intergroup inequality. Using a twin design (n = 1,987), we investigate whether the desire for intergroup dominance and inequality makes up a genetically grounded behavioral syndrome. Specifically, we investigate the heritability of SDO, in addition to whether it genetically correlates with support for political policies concerning the distribution of power and resources to different social groups. In addition to moderate heritability estimates for SDO-D and SDO-E (37% and 24%, respectively), we find that the genetic correlation between these subdimensions and political attitudes was overall high (mean genetic correlation 0.51), while the environmental correlation was very low (mean environmental correlation 0.08). This suggests that the relationship between political attitudes and SDO-D and SDO-E is grounded in common genetics, such that the desire for (versus opposition to) intergroup inequality and support for political attitudes that serve to enhance (versus attenuate) societal disparities form convergent strategies for navigating group-based dominance hierarchies.


Assuntos
Atitude , Personalidade/genética , Predomínio Social , Identificação Social , Gêmeos Monozigóticos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia
13.
Transl Psychiatry ; 9(1): 21, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30655504

RESUMO

The genetic architecture of schizophrenia (SCZ) includes numerous risk loci across a range of frequencies and sizes, including common and rare single-nucleotide variants and insertions/deletions (indels), as well as rare copy number variants (CNVs). Despite the clear heritability of the disease, monozygotic twins are discordant for SCZ at a significant rate. Somatic variants-genetic changes that arise after fertilization rather than through germline inheritance-are widespread in the human brain and known to contribute to risk for both rare and common neuropsychiatric conditions. The contribution of somatic variants in the brain to risk of SCZ remains to be determined. In this study, we surveyed somatic single-nucleotide variants (sSNVs) in the brains of controls and individuals with SCZ (n = 10 and n = 9, respectively). From each individual, whole-exome sequencing (WES) was performed on DNA from neuronal and non-neuronal nuclei isolated by fluorescence activated nuclear sorting (FANS) from frozen postmortem prefrontal cortex (PFC) samples, as well as DNA extracted from temporal muscle as a reference. We identified an increased burden of sSNVs in cases compared to controls (SCZ rate = 2.78, control rate = 0.70; P = 0.0092, linear mixed effects model), that included a higher rate of non-synonymous and loss-of-function variants (SCZ rate = 1.33, control rate = 0.50; P = 0.047, linear mixed effects model). Our findings suggest sSNVs in the brain may constitute an additional component of the complex genetic architecture of SCZ. This perspective argues for the need to further investigate somatic variation in the brain as an explanation of the discordance in monozygotic twins and a potential guide to the identification of novel therapeutic targets.


Assuntos
Encéfalo/patologia , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Esquizofrenia/patologia , Gêmeos Monozigóticos/genética , Sequenciamento do Exoma
14.
J Stud Alcohol Drugs ; 79(5): 725-732, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30422786

RESUMO

OBJECTIVE: Adolescence is an optimal developmental stage for examining the interplay of environmental factors and the genetic risk for alcohol involvement. The current study aimed to examine how socioeconomic status might interact with genetic risk for alcohol involvement among adolescents. METHOD: A total of 839 same-sex adolescent twin pairs (509 monozygotic and 330 dizygotic) from the 1962 National Merit Twin Study completed a questionnaire containing items assessing alcohol involvement. Twins were approximately 17 years old at the time of participation. Parents provided reports of family income and educational attainment. Models were fit examining parental education and family income as moderators of genetic and environmental influences on alcohol use. RESULTS: There was evidence for moderation of genetic and environmental influences on alcohol involvement by family income. For twins with the lowest levels of family income, genetic and shared environmental influences accounted for 50% and 26% of the variance in alcohol involvement, respectively, compared with 2% and 67% of the variance among those at the highest level of income. CONCLUSIONS: These findings suggest that etiological influences on alcohol involvement vary as a function of an adolescent's socioeconomic status.


Assuntos
Interação Gene-Ambiente , Classe Social , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/psicologia , Consumo de Álcool por Menores/economia , Consumo de Álcool por Menores/psicologia , Adolescente , Feminino , Humanos , Masculino , Pais/psicologia , Fatores de Risco , Inquéritos e Questionários , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
15.
PLoS One ; 13(8): e0202518, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30142159

RESUMO

Political participation (POP), social participation (SOP), and political interest (PI) are important indicators of social status and social inequality. Previous studies on related trait differences yielded genetic and environmental contributions. However, focusing on adult samples, classical twin designs, and convenience samples often restricts parameter estimation and generalizability, and limits the understanding of age differences. We investigated sources of variance in POP, SOP, and PI in late adolescence and early adulthood with an extended twin family design (ETFD). We analyzed data from over 2,000 representative German twin families. Individual environments not shared by family members reflected the major source of variance for all variables, but genetic influences were also pronounced. Genetic effects were mostly higher for young adults, whereas effects of twins' shared environment were significant in adolescence. Our study deepens the understanding of the interplay between genetic and environmental factors in shaping differences in young persons' integration in society.


Assuntos
Ativismo Político , Política , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/psicologia , Adolescente , Adulto , Feminino , Interação Gene-Ambiente , Alemanha , Humanos , Masculino , Meio Social , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto Jovem
16.
Behav Genet ; 48(4): 337-349, 2018 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.


Assuntos
Causalidade , Análise da Randomização Mendeliana/métodos , Modelos Genéticos , Estudos em Gêmeos como Assunto/métodos , Interação Gene-Ambiente , Pleiotropia Genética , Variação Genética , Humanos , Método de Monte Carlo , Herança Multifatorial , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
17.
Twin Res Hum Genet ; 21(3): 269-274, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29792247

RESUMO

Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28-31 weeks) and mid-third trimester (32-35 weeks). Fetal presentation was categorized as vertex or non-vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this 'no change' group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable.


Assuntos
Peso ao Nascer/genética , Feto/embriologia , Terceiro Trimestre da Gravidez , Gravidez de Gêmeos , Gravidez , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino
18.
Twin Res Hum Genet ; 21(2): 146-154, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29582724

RESUMO

Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.


Assuntos
Genótipo , Inquéritos e Questionários , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur Psychiatry ; 46: 51-56, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29017064

RESUMO

There is growing evidence of an association between negative social comparisons (NSC) and both psychosis, and psychosis proneness. The majority of the work thus far, however, has focused largely on one type of NSC, namely, social rank. Whilst social rank is clearly an important factor, an individual's perception of belonging is likely also of importance; particularly, when considering individuals from collectivistic cultures such as China, where greater emphasis is placed on fitting into the group. There is also limited research investigating what factors may contribute towards the relationship between NSC and psychosis proneness, and to what extent this relationship may be due to common familial factors. To address these issues, we examined whether (1) Social rank and perceived belonging predict negative, positive and depressive psychotic experiences in a Chinese, adolescent, twin and sibling population, (2) coping styles moderate the impact of these relationships and (3), there is a familial association between NSC and psychosis proneness. Both social rank and perceived belonging were found to predict the negative and depressive dimensions of psychosis. These relationships were moderated by problem-focused coping styles. Interestingly, the association between perception of belonging, and negative psychotic experiences was familial-and stronger in Monozygotic twins-indicating perhaps shared aetiology due to common genes. Our findings highlight NSC as potential vulnerability markers for negative and depressive psychotic experiences, and suggest potentially different aetiological pathways amongst different NSC and different psychotic experiences. On a clinical level, our findings emphasize the need to consider coping styles when treating at-risk individuals.


Assuntos
Adaptação Psicológica , Suscetibilidade a Doenças , Transtornos Psicóticos/genética , Transtornos Psicóticos/psicologia , Classe Social , Adolescente , China , Feminino , Voluntários Saudáveis , Humanos , Masculino , Transtornos Psicóticos/etiologia , Irmãos/psicologia , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia
20.
Sleep ; 39(1): 67-77, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26285009

RESUMO

STUDY OBJECTIVES: We used quantitative genetic models to assess whether area-level deprivation as indicated by the Singh Index predicts shorter sleep duration and modifies its underlying genetic and environmental contributions. METHODS: Participants were 4,218 adult twin pairs (2,377 monozygotic and 1,841 dizygotic) from the University of Washington Twin Registry. Participants self-reported habitual sleep duration. The Singh Index was determined by linking geocoding addresses to 17 indicators at the census-tract level using data from Census of Washington State and Census Tract Cartographic Boundary Files from 2000 and 2010. Data were analyzed using univariate and bivariate genetic decomposition and quantitative genetic interaction models that assessed A (additive genetics), C (common environment), and E (unique environment) main effects of the Singh Index on sleep duration and allowed the magnitude of residual ACE variance components in sleep duration to vary with the Index. RESULTS: The sample had a mean age of 38.2 y (standard deviation [SD] = 18), and was predominantly female (62%) and Caucasian (91%). Mean sleep duration was 7.38 h (SD = 1.20) and the mean Singh Index score was 0.00 (SD = 0.89). The heritability of sleep duration was 39% and the Singh Index was 12%. The uncontrolled phenotypic regression of sleep duration on the Singh Index showed a significant negative relationship between area-level deprivation and sleep length (b = -0.080, P < 0.001). Every 1 SD in Singh Index was associated with a ∼4.5 min change in sleep duration. For the quasi-causal bivariate model, there was a significant main effect of E (b(0E) = -0.063; standard error [SE] = 0.30; P < 0.05). Residual variance components unique to sleep duration were significant for both A (b(0Au) = 0.734; SE = 0.020; P < 0.001) and E (b(0Eu) = 0.934; SE = 0.013; P < 0.001). CONCLUSIONS: Area-level deprivation has a quasi-causal association with sleep duration, with greater deprivation being related to shorter sleep. As area-level deprivation increases, unique genetic and nonshared environmental residual variance in sleep duration increases.


Assuntos
Meio Ambiente , Sono/genética , Sono/fisiologia , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/estatística & dados numéricos , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/estatística & dados numéricos , Adulto , Censos , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Modelos Genéticos , Sistema de Registros , Autorrelato , Fatores Socioeconômicos , Fatores de Tempo , Washington , População Branca/genética
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