Biomedical subjects

Lindon J Eaves

Publications and source records attributed to Lindon J Eaves.

At least 19 recordsLinked to original sources

PubMed2006

Genetic and cultural transmission of smoking initiation: an extended twin kinship model.

BACKGROUND: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a significant role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. METHODS: We examined the role of genetic and environmental factors for smoking initiation using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission. A dichotomous lifetime smoking measure was obtained from twins and relatives in the Virginia 30,000 sample. RESULTS: Results demonstrate that both genetic and environmental factors play a significant role in the liability to smoking initiation. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission and resulting genotype-environment covariance. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (i) age x gene interaction, and (ii) social homogamy. Neither mechanism provided a significantly better explanation of the data, although age regression was significant. CONCLUSIONS: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on smoking initiation.

Aged↗

PubMed2006

Multivariate adaptive regression splines: a powerful method for detecting disease-risk relationship differences among subgroups.

In a wide variety of medical research scenarios one is interested in the question whether regression curves differ for subgroups in the sample. Examples are gender differences in the effect of drug treatment or the study of genotype-environment interactions. To address this question exploratory techniques are often required because detailed knowledge concerning the shape of the regression curves and how that shape differs across subgroups is lacking. In this article we explored the power of two such exploratory techniques: multivariate adaptive regression splines (MARS) and least squares curve fitting using polynomials. For this purpose simulations were performed using linear, logistic, and complex non-linear curves. The power obtained from MARS was on average 1.4 times higher than with polynomials. It was shown that power was higher even if the regression curve was linear, that gains increased with the complexity of the curve, and that for highly non-linear curves model-free methods such as MARS might be the only alternative.

Biometry↗

PubMed2006

Genotype x Environment interaction in psychopathology: fact or artifact?

Recent studies have claimed to detect interaction between candidate genes and specific environmental factors (Genotype x Environment interaction, G x E) in susceptibility to psychiatric disorder. The objective of the present study was to examine possible artifacts that could explain widely publicized findings. The additive effects of candidate genes and measured environment on liability to disorder were simulated under a model that allowed for mixture of distributions in liability conditional on genotype and environment. Simulated liabilities were dichotomized at a threshold value to reflect diagnosis of disorder. Multiple blocks of simulated data were analyzed by standard statistical methods to test for the main effects and interactions of genes and environment on outcome. The main outcome of this study was simulated liabilities and diagnoses of major depression and antisocial behavior. Analysis of the dichotomized data by logistic regression frequently detected significant G x E interaction even though none was present for liability. There is therefore reason to question the biological significance of published findings.

Artifacts↗

PubMed2005

cDNA microarray analysis identifies genes induced in common by peptide growth factors and androgen in human prostate epithelial cells.

Prostate cancer cells initially require androgen for continued proliferation, but invariably become androgen independent or unresponsive and recur after treatment by androgen ablation. Exploitation of common signaling components downstream of their specific receptors (i.e., androgen receptor (AR), insulin-like growth factor 1 (IGF-1) receptor, and epidermal growth factor (EGF) receptor) could provide a mechanism by which androgen independent cells survive and proliferate. Our objective was to design and implement prostate enriched cDNA microarrays to identify genes induced in prostate epithelial cells in a similar temporal pattern by both androgen and IGF or EGF. AR positive and AR negative human prostate epithelial cells of the M12 line were exposed in parallel to DHT, EGF, or IGF for 0, 6, or 24 h. RNA extracted from each of these groups was analyzed by cDNA microarrays composed of a unique set of 6373 prostate-derived cDNA clones from the Prostate Expression Database (PEDB). We observed statistically significant changes in 20 genes induced in common after 6 and 24 h exposure to androgen or these growth factors, and validated the microarray results by RT-PCR for three or four of these genes: v-myc, isocitrate dehydrogenase, and calnexin. Androgen response element binding motifs were identified in the upstream sequence in 16 of these 20 genes. These results provide comprehensive and unique insights into potential mechanisms by which peptide growth factors provide alternate pathways to control prostate epithelial cell proliferation in malignant states.

Biomarkers, Tumor↗

PubMed2005

Parent-child feedback predicts sibling contrast: using twin studies to test theories of parent-offspring interaction in infant behavior.

Several studies report apparent sibling contrast effects in analyses of twin resemblance. In the presence of genetic differences, contrast effects reduce the dizygotic (DZ) twin correlation relative to that in monozygotic (MZ) twins and produce higher DZ than MZ variance. Explanations of contrast effects are typically cast in terms of direct social interaction between twins or an artifact of the process of rating children by their parents. We outline a model for sibling imitation and contrast effects that depends on social interaction between parents and children. In addition to predicting the observed pattern of twin variances and covariances, the parental mediation of child imitation and contrast effects leads to differences in the variance of parents of MZ and DZ twins and differences between the correlations of parents with their MZ and DZ children.

Biofeedback, Psychology↗

PubMed2005

Epistatic and environmental control of genome-wide gene expression.

All etiological studies of complex human traits focus on analyzing the causes of variation. Given this complexity, there is a premium on studying those processes that mediate between gene products and cellular or organismal phenotypes. Studies of levels of gene expression could offer insight into these processes and are likely to be especially useful to the extent that the major sources of their variation are known in normal tissues. The classical study of monozygotic (MZ) and dizygotic (DZ) twins was employed to partition the genetic and environmental influences in gene expression for over 6500 human genes measured using microarrays from lymphoblastoid cell lines. Our results indicate that mean expression levels are correlated about .3 in monozygotic (MZ) and .0 in dizygotic (DZ) twins suggesting an overall epistatic regulation of gene expression. Furthermore, the functions of several of the genes whose expression was most affected by environmental effects, after correction for measurement error, were consistent with their known role in mediating sensitivity to environmental influences.

Adolescent↗

PubMed2005

Revisiting the children of twins: can they be used to resolve the environmental effects of dyadic parental treatment on child behavior?

The children of twins (COT) design has been proposed as an alternative to the adoption study to resolve the direct effects of parental treatment from secondary parent-child association due to genetic factors. The basic analytical approach compares the parent-offspring correlation with the correlation between children and the monozygotic (MZ) twins of their parents. We show that a significant difference between these correlations does not imply direct environmental causality when the measured parental treatment in question is dyadic, that is, influenced by both parents even when mating is random. Nongenetic causal effects yield very similar patterns of correlation to secondary genetic effects on dyadic treatment variables. The fact that many candidate environments, such as parental divorce, are dyadic gives reason to question the interpretation of their correlations with behavior in the children of twins.

Environment↗

PubMed2005

Genetic and environmental influences on temperament in the first year of life: the Puerto Rico Infant Twin Study (PRINTS).

Three dimensions of temperament -- difficult temperament, unadaptablility and unsociability -- were assessed in the first year of life by maternal interview in twins born in Puerto Rico during 2001 and 2002. Eight hundred and sixty-five eligible mothers (80%) were traced and interviewed. Model-fitting results showed that additive genetic factors and the individual specific environment contributed to variation in all three dimensions. In addition, the pattern of variances and correlations suggested that sibling contrast effects influence ratings of difficult temperament. Moderate effects of the shared environment contributed to ratings of adaptability and sociability. There was a significant genetic correlation between difficult temperament and unadaptability. Genetic and environmental effects do not differ significantly between boys and girls. The study is the first population-based study of Puerto Rican twins and one of few to attempt the assessment of behavior in the first year. Preliminary results for difficult temperament and sociability were consistent with those in other populations and ages. In contrast, a significant effect of the shared environment on the temperamental trait of unadaptability has not been reported previously.

Environment↗

PubMed2005

Familial influences on alcohol use in adolescent female twins: testing for genetic and environmental interactions.

OBJECTIVE: Both genetic and common environmental influences contribute to twin associations for substance use; however, twin concordance rates may vary by environmental setting, indicating the presence of genetic-environmental interactions. The present study examined whether measures of family adaptability and cohesion may moderate the genetic influence on risk for alcohol use among female adolescents. METHOD: We examined such interactions through the application of log-linear models using data from the Virginia Twin Study of Adolescent Behavioral Development, a longitudinal study with extensive home interviews of adolescent (8-17 year old) female twins (386 monozygotic [MZ] pairs, 185 dizygotic [DZ] pairs) and their parents. RESULTS: Twin concordance for alcohol use varied by average twin/parent reports of parental closeness. Differences between MZ-DZ correlations for alcohol use in families with low parental closeness, for example, were 0.97 and 0.67 (p < .001), respectively, compared with 0.79 and 0.73 (p = .24) for high parental closeness families. In addition, differences in twin concordance regardless of zygosity were found with greater twin similarities for alcohol use in strict families compared with leniently disciplined families, suggesting that the twin association interacts with common environmental influences on alcohol use. CONCLUSIONS: These results indicate that the genetic effects on adolescent alcohol use interact with the measured family environment and that the heritability of alcohol use may vary according to quality of the parental relationship. If confirmed, prevention programs may benefit from this knowledge, tailoring their intervention to quality of parental relationship.

Adolescent↗

PubMed2004

Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder.

BACKGROUND: Very little is known about how different sets of risk factors interact to influence risk for psychiatric disorder. OBJECTIVE: To replicate a recent report of a genotype-environment interaction that predicts risk for antisocial behavior in boys. DESIGN: Characterizing risk for conduct disorder in boys in association with monoamine oxidase A genotype and exposure to familial adversity, defined by interparental violence, parental neglect, and inconsistent discipline. SETTING: A community-based sample of twin boys. PARTICIPANTS: Five hundred fourteen male twins aged 8 to 17 years. MAIN OUTCOME MEASURE: Conduct disorder. RESULTS: There was a main effect of adversity but not of monoamine oxidase A on risk for conduct disorder. Low monoamine oxidase A activity increased risk for conduct disorder only in the presence of an adverse childhood environment. Neither a passive nor an evocative genotype-environment correlation accounted for the interaction. CONCLUSION: This study replicates a recent report of a genotype-environment interaction that predicts individual variation in risk for antisocial behavior in boys.

Adolescent↗

PubMed2004

A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence.

BACKGROUND: Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary. METHOD: We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry. RESULTS: The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80 % of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75 %, 80 % and 60 % respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females. CONCLUSIONS: This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND.

Adult↗

PubMed2004

Course and short-term outcomes of separation anxiety disorder in a community sample of twins.

OBJECTIVE: To assess the course and short-term outcomes associated with separation anxiety disorder (SAD) in a community setting. METHOD: The subjects were 161 of 2,061 8- to 17-year-old twins with SAD from a community-based twin study. Subjects were born between 1974 and 1983. Subjects and parents were personally interviewed about the subject's current psychiatric history between 1990 and 1993. A follow-up interview was conducted, on average, 18 months later. Logistic regression was used to identify predictors and outcomes of persistent SAD. RESULTS: Of the 161 subjects with SAD at time 1, 80% had remitted and 59% were free of any disorder at follow-up. Children with persistent SAD had a significantly higher prevalence of oppositional defiant disorder, significantly more impairment associated with symptoms of attention-deficit/hyperactivity disorder, and mothers who were less satisfied with their marriage at time 1 than children with transient episodes. Children with persistent SAD had a significantly higher prevalence of overanxious disorder or a new minor or major depressive disorder at time 2 than children with transient SAD. After controlling for comorbidity, only an elevated risk of new depressive disorders at time 2 distinguished children with persistent SAD. CONCLUSIONS: Many children with SAD in a community setting are well at follow-up, on average, 18 months later. A minority of children with persistent SAD are at significantly increased risk of a new depressive disorder, especially those with a history of oppositional defiant disorder, impairment associated with symptoms of attention deficit hyperactivity disorder, or parental marital difficulties.

Adolescent↗

PubMed2004

Risks for conduct disorder symptoms associated with parental alcoholism in stepfather families versus intact families from a community sample.

BACKGROUND: It is not known if the prevalence of parental psychiatric disorders is higher in stepfather than intact families, or if parental alcoholism is differentially associated with risk for conduct disorder (CD) symptoms in stepfather families versus intact families. METHOD: The sample comprised 839 girls and 741 boys from 792 intact families and 99 girls and 67 boys from 83 stepfather families from a population-based registry of twins aged between 8 and 17 years. Children's current psychiatric symptoms were assessed at personal interview with the child, mother and father. Parental histories of psychiatric disorder were assessed at personal interview with each residential parent. Associations between CD symptoms and parental alcoholism were characterized using both linear and Poisson regression, and results are presented with and without adjustment for maternal drug use during pregnancy, parental conflict, and estimated socioeconomic status (SES) based on census tract data. RESULTS: Mothers from stepfather families had a higher lifetime prevalence of alcoholism, antisocial personality disorder, depression and social phobia than mothers from intact families. Stepfathers had a higher lifetime prevalence of alcoholism and depression than biological fathers from intact families. Children from stepfather families had more externalizing (CD/ODD) symptoms than children from intact families. Girls who lived with an alcoholic stepfather had significantly more CD symptoms than girls who lived with an alcoholic biological father. Boys who lived with an alcoholic stepfather had significantly fewer CD symptoms than boys who lived with an alcoholic biological father. This sex difference was statistically significant. Adjustment for maternal drug use during pregnancy, parental conflict, and estimated SES based on census tract data did not change these findings. CONCLUSIONS: Children living in stepfather families are exposed to more parental psychiatric risk factors than children from intact families. The increased risk for CD symptoms in girls (but not boys) from stepfather families is partly mediated by or associated with the stepfather's history of alcoholism.

Adolescent↗

PubMed2003

Maternal smoking during pregnancy and risk to boys' conduct disturbance: an examination of the causal hypothesis.

BACKGROUND: We undertook this study to determine whether the widely replicated link between maternal smoking and conduct disturbance (Cd) is better explained by a model of direct causation or of mother-offspring transmission of a latent Cd variable. METHODS: Family data collected on 538 adolescent twin boys from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to compare two alternative models: 1) a model composed of a latent transmissible factor that influences mother's juvenile conduct symptoms, smoking during pregnancy, and subsequent Cd and smoking in her adolescent boys; and 2) a model specifying a direct causal path from mother's smoking to child Cd. RESULTS: The maternal-offspring transmission model fit the data as well as a model specifying a direct causal path from maternal smoking to child Cd. CONCLUSIONS: Our results suggest that the association between maternal smoking during pregnancy and boys' Cd symptoms may be attributed to the transmission of a latent Cd factor and not to a direct effect of the smoking. Our results challenge previous findings of a direct effect of prenatal smoke exposure on risk to Cd once other etiologic factors are considered.

Adolescent↗

PubMed2003

Modulation of gene expression by genetic and environmental heterogeneity in timing of a developmental milestone.

The expression of many important behavioral outcomes is contingent on passing a developmental milestone, such as puberty, or exposure to an age-dependent risk factor, such as alcohol or drugs. Current models for genetic effects on development have not provided explicit theoretical insight about possible patterns of epistasis and genotype x environment interaction generated by genetic and environmental heterogeneity in the timing of developmental milestones that influence gene expression. We explore theoretically the effects of individual differences in the timing of a developmental milestone on the expression of genetic differences in outcome. The consequences of additive genetic variation and shared environmental variation on timing are examined. Additive genetic effects on timing generate transient epistatic effects on outcome because they modulate the expression of otherwise additive genetic differences in outcome. Epistatic effects will be greatest at ages when there is the most heterogeneity in developmental maturity. Epistasis will gradually disappear as proportionately more individuals mature. Similarly, shared environmental effects on the timing of a milestone will generate transient genotype x shared environment interaction appearing as shared environmental effects on outcome that are greatest when there is the most heterogeneity in developmental maturity. The impact of these effects on age patterns in twin correlations is examined and their relevance to current data on developmental change discussed briefly.

Adolescent↗

PubMed2003

The role of the children of twins design in elucidating causal relations between parent characteristics and child outcomes.

BACKGROUND: Determination of causal connections between parental measures and child outcomes using typical samples is limited by the inability to account for all confounds, both environmental and genetic. This paper discusses the strength of the Children of Twins (COT) design to highlight the role of specific environments. METHODS: A new analytical model is presented which helps differentiate and quantify the environmental and genetic processes underlying associations between family-level risk factors and child adjustment. In order to illustrate the COT design, the relation between smoking during pregnancy and child birth weight (BW) is examined in a sample of female twins and their children from Norway and the United States. RESULTS: The results illustrate that smoking during pregnancy is influenced by genetic factors. However, the Children of Twins model supports the claim that smoking during pregnancy has a direct environmental influence on BW and that genetic and shared environmental confounds cannot account for the association. CONCLUSIONS: An assessment of the strengths and limitations of the Children of Twins design and a comparison with other research strategies suggest that the design plays a unique role in the study of developmental psychology and psychopathology. Finally, the authors describe how methodological advances and future applications of the design will provide additional insight into the causal processes underlying children's adjustment to environmental stimuli.

Adult↗

PubMed2002

Evaluation of analyses of univariate discrete twin data.

Akiake's Information Criterion (AIC) is commonly used in univariate twin modeling of a discrete trait to prune a full model into a more parsimonious submodel. It is possible that this practice could introduce bias and inaccuracy, and we could identify no prior systematic study of these issues. Thus, we used simulation to investigate the performance of AIC-guided modeling across a broad range of parameters. Our simulations indicated that the use of the AIC to determine the "best" univariate model for a discrete trait tended to yield the incorrect model rather frequently. Moreover the parameter estimates of the "best" model by AIC were biased sharply upward as were the associated 95% confidence intervals. These results suggest that the use of AIC to guide twin modeling for univariate discrete traits should either be abandoned or used with great caution.

Bias↗

PubMed2002

Assessment of the within-family environment in twins: absolute versus differential ratings, and relationship with conduct problems.

BACKGROUND: The aim was to compare the psychometric properties of absolute versus differential ratings of the within-family environments and to examine their associations with conduct problems in 8-16-year-old twins. METHODS: The sample comprised 1117 pairs of like-sex male and female twins and their parents, recruited from the school population of Virginia. The within-family environment was assessed from the Twin Inventory of Relationships and Experiences (TIRE), which provided measures of differential parental criticism, parental preference for one twin, and twins' peers' conduct problems, as rated by mothers, fathers and each of the twins. Twins' conduct problems were assessed by a modified version of the Olweus questionnaire. RESULTS: Although differential ratings and absolute ratings had similar psychometric properties, the use of absolute ratings to differentiate the twins resulted in a construct with weak inter-rater agreement and low stability over time. Differential ratings of the twins' environment showed significant associations with differences in conduct problems between the twins, whereas the difference in absolute ratings of each twin did not. The differential parental criticism effect was uninfluenced by the overall level of criticism in the family. CONCLUSIONS: A direct contrast between siblings or twins, as part of the rating procedure (as provided by differential ratings), may be a more efficient way to assess aspects of the within-family environment that are reliable and which are associated with psychopathology. Both differential parental criticism and peers' conduct disturbance were associated with conduct problems in the twins.

Adolescent↗