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PubMed1981

Neurobiological approaches in human behavior genetics.

An attempt should be made to base analysis of problems in human behavior genetics on existing knowledge of human biochemical genetics and neurobiology. Examples for this approach are studies showing HY antigen patterns of the opposite sex in transsexuality, slight psychological deviations in heterozygotes of recessive metabolic diseases such as phenylketonuria and lipid storage diseases, and psychological studies in healthy individuals with various genetic variants of the normal human electroencephalogram (EEG). Results of such studies will help gradually to replace emotional controversy by rational assessment of facts.

Brain↗
PubMed1985

Further considerations for behavior-genetic analysis of humans.

In this reply to Plomin and Foch (1985) we maintain that the five specific points we criticized in their behavior-genetic analysis of personality are still important (Haviland, McGuire, & Rothbaum, 1983). In addition, we briefly describe three relevant issues in experimental behavior-genetic studies as they apply to correlational behavior-genetic studies of human personality.

Genetics, Behavioral↗
PubMed1997

Putting the behavior into the behavior genetics of obesity.

Tremendous advances in the genetic underpinnings of obesity have emerged in recent years. Curiously, behavioral genetic methods have provided relatively less information on the environmental influences and intermediary behaviors which promote human obesity. This situation in unfortunate since human obesity is, in part, environmentally determined and the result of behaviors such as eating and physical (in)activity. This article has several goals. First, it outlines reasons why behavior qua behavior should be a specific focus of obesity-oriented behavioral genetic designs. Second, possible explanations for why behavior has been underinvestigated are explored. Third, data regarding the genetic/ environmental architecture of various obesity-related phenotypes (e.g., food intake, physical activity, etc.) are reviewed. Fourth, a commentary on the importance of gene-environment interactions is offered. Finally, suggestions for future research, including a list of possible "candidate environments" and "candidate intermediary behaviors," are offered.

Adolescent↗
PubMedDate not supplied

Behavioral genetics of food intake regulation in free-living humans.

It has been established that the genes influence body size. Recently, it has become clear that food intake is also influenced by heredity. Surprisingly, the genetic effect on intake was found to occur independent of body size. Taking height and body weight into consideration, strong influences of heredity were found on the total amounts of food energy, macronutrients, and fluids ingested. Also, genetic influences were found related to the microstructure of intake, affecting the number, timing, and composition of meals. Since overall intake is determined by the size and frequency of meals, this was not surprising. However, these heritable factors were shown to influence meal size and frequency even when overall daily intake was considered in the model. Recently, we have shown that there are even heritable factors that influence the choice of the environmental conditions at the meals; the time, degree of hunger, stomach fullness, and the number and type of people at the meal. Also the degree to which these conditions affect intake appears to be heritable. These findings suggest that there are important heritable factors that influence body size, overall daily intake independent of body size, meal intake independent of overall daily intake, and the selection of and responsivity to the environmental conditions surrounding eating.

Adult↗
PubMed1998

Assessing the effects of cooperation bias and attrition in behavioral genetic research using data-weighting.

Because twins and adoptees are a rare resource, they are often studied repeatedly over a period of many years. Differential attrition, and in some studies initial cooperation bias, have the potential to lead to serious biases to estimates of genetic and environmental parameters. Since non-response is often influenced by multiple binary or categorical sociodemographic variables, maximum-likelihood methods are not easily adapted to adjust for such effects. In this brief note we illustrate the use of data-weighting to assess the likely effects of cooperation bias or attrition both on measures of mean or prevalence, and on twin pair correlations or concordances, using data from the Australian twin panel 1981 survey and alcohol challenge studies. Participants in the alcohol challenge study were on average younger, more socially nonconforming, heavier drinkers, more likely to be unmarried, and less likely to report their religion as Other Protestant. Reweighting the alcohol challenge sample to have the same distribution on these variables as the Australian twin panel 1981 survey respondents confirmed that individuals who would feel very intoxicated after a challenge dose of alcohol were underrepresented in the study. However, pairwise data-weighting indicated that this cooperation bias was leading to only a slight underestimation of the importance of genetic effects on subjective intoxication.

Adoption↗
PubMed2006

Advances in behavioral genetics modeling using Mplus: applications of factor mixture modeling to twin data.

This article discusses new latent variable techniques developed by the authors. As an illustration, a new factor mixture model is applied to the monozygotic-dizygotic twin analysis of binary items measuring alcohol-use disorder. In this model, heritability is simultaneously studied with respect to latent class membership and within-class severity dimensions. Different latent classes of individuals are allowed to have different heritability for the severity dimensions. The factor mixture approach appears to have great potential for the genetic analyses of heterogeneous populations. Generalizations for longitudinal data are also outlined.

Adult↗
PubMed1995

Behavior genetic investigation of the relationship between spontaneous locomotor activity and the acquisition of morphine self-administration behavior.

There is a significant degree of individual variability in response to drugs of abuse. A goal of behavior genetic studies has been to determine the extent to which observed heterogeneity in drug use can be attributed to genetic and environmental factors and to identify the neurobiological factors involved in vulnerability. Recent hypotheses regarding the predictive value of spontaneous locomotor activity in the acquisition of drug-reinforced behavior are amenable to testing using a behavior genetics approach. Genetic differences in locomotor response to a novel environment were determined in naive and catheterized Lewis, F344, NBR and ACI rats. Operant drug-reinforced behavior was examined in a 23h access paradigm in which each lever press by a rat produced a 1mg/kg injection of morphine with a 30s timeout period (FR 1:TO 30"). Acquisition (7 days), extinction (6 days) and reacquisition (7 days) of morphine self-administration behavior was investigated in all four inbred strains. Large genetic differences in the rate of acquisition and extinction of morphine self-administration were found. Lewis rats responded at high rates beginning in the first two days, whereas F344 rats initially responded at low rates and responding increased gradually over seven days. NBR and ACI rats responded at intermediate levels. When vehicle was substituted for drug there was a significant effect of genotype on the rate of extinction; F344 and ACI increased responding to greater than 175% of drug-response levels, whereas the Lewis response rate decreased gradually and NBR response rate decreased immediately during the first several days. When drug was available again, rates of reacquisition did not differ from original acquisition rates. Drug maintained significantly greater amounts of behavior than vehicle in the Lewis, F344 and NBR rats and was thus shown to serve as a positive reinforcer in these three strains under these conditions. There was a significant genetic correlation among strains between drug intake during the first five days of acquisition and spontaneous locomotor response to a novel environment in catheterized rats. Only the ACI rats showed a significant within-strain correlation. The positive relationship between rate of acquisition of self-administration behavior and locomotor activity suggests that these two traits are influenced by common or closely linked genes. To this end, the neurobiological substrates that mediate spontaneous locomotor behavior under these environmental conditions may act, in part, as a template for determining the neurobiological substrates that mediate the relative rate of acquisition of morphine-taking behavior under these conditions.

Journal Article↗
PubMed2006

Combined application of behavior genetics and microarray analysis to identify regional expression themes and gene-behavior associations.

In this report we link candidate genes to complex behavioral phenotypes by using a behavior genetics approach. Gene expression signatures were generated for the prefrontal cortex, ventral striatum, temporal lobe, periaqueductal gray, and cerebellum in eight inbred strains from priority group A of the Mouse Phenome Project. Bioinformatic analysis of regionally enriched genes that were conserved across all strains revealed both functional and structural specialization of particular brain regions. For example, genes encoding proteins with demonstrated anti-apoptotic function were over-represented in the cerebellum, whereas genes coding for proteins associated with learning and memory were enriched in the ventral striatum, as defined by the Expression Analysis Systematic Explorer (EASE) application. Association of regional gene expression with behavioral phenotypes was exploited to identify candidate behavioral genes. Phenotypes that were investigated included anxiety, drug-naive and ethanol-induced distance traveled across a grid floor, and seizure susceptibility. Several genes within the glutamatergic signaling pathway (i.e., NMDA/glutamate receptor subunit 2C, calmodulin, solute carrier family 1 member 2, and glutamine synthetase) were identified in a phenotype-dependent and region-specific manner. In addition to supporting evidence in the literature, many of the genes that were identified could be mapped in silico to surrogate behavior-related quantitative trait loci. The approaches and data set described herein serve as a valuable resource to investigate the genetic underpinning of complex behaviors.

Alcoholism↗
PubMed2003

Tilting at Twindmills: rethinking sociological responses to behavioral genetics.

While we commend Horwitz et al. (2003) for speaking to core issues in behavioral genetics, we disagree with many particulars of their article. We are skeptical of their claims regarding the particular contribution offered by both their methods and data. We believe also that the findings they present as challenging the equal environments assumption are, upon closer examination, not persuasive. Most fundamentally, we worry that the way in which Horwitz et al. conceptualize the relationship between genes and environments is not the best means of doing so for sociologists interested in engaging behavioral genetics.

Adolescent↗
PubMed2006

Likelihood ratio tests in behavioral genetics: problems and solutions.

The likelihood ratio test of nested models for family data plays an important role in the assessment of genetic and environmental influences on the variation in traits. The test is routinely based on the assumption that the test statistic follows a chi-square distribution under the null, with the number of restricted parameters as degrees of freedom. However, tests of variance components constrained to be non-negative correspond to tests of parameters on the boundary of the parameter space. In this situation the standard test procedure provides too large p-values and the use of the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC) for model selection is problematic. Focusing on the classical ACE twin model for univariate traits, we adapt existing theory to show that the asymptotic distribution for the likelihood ratio statistic is a mixture of chi-square distributions, and we derive the mixing probabilities. We conclude that when testing the AE or the CE model against the ACE model, the p-values obtained from using the chi(2)(1 df) as the reference distribution should be halved. When the E model is tested against the ACE model, a mixture of chi(2)(0 df), chi(2)(1 df) and chi(2)(2 df) should be used as the reference distribution, and we provide a simple formula to compute the mixing probabilities. Similar results for tests of the AE, DE and E models against the ADE model are also derived. Failing to use the appropriate reference distribution can lead to invalid conclusions.

Analysis of Variance↗
PubMed1996

Stability and change in personality across the life span: behavioral-genetic versus evolutionary approaches.

Recent findings and theoretical models of behavioral-genetic and evolutionary approaches to personality development across the life span are presented. Theoretical and empirical strengths and weaknesses of these approaches regarding the issue of stability and change are outlined. Although these "biological" models may appear disparate as often as they appear similar, they share the common assumption that most personality phenomena are products of environmental contingencies. However, they differ with regard to the level at which they analyze and incorporate environmental influences into their interpretations of stability and change. Genetic influences are also examined. A theoretical integration of the recent findings and of the models of genetic and environmental influences on personality via evolutionary and behavioral-genetic approaches is intended to fill in the gaps and stimulate research on the study of personality development across the life span.

Adolescent↗
PubMed1993

Invited commentary: cryopreservation as a tool for the study of selectively bred lines in rodent behavioral genetics.

Cryopreserved embryos should survive centuries. Upon rederivation, in vitro survival is high. Upon reimplantation, in vivo survival is substantial. Genetic stability of the embryos at -196 degrees C is theoretically absolute for several decades and likely high for centuries. Cryopreservation and rederivation services are available at a reasonable cost from commercial vendors. Preservation of a sufficient number of embryos can serve as an insurance policy against loss of the lines from several causes. In addition to the protective utility of a single banked sample, repeated preservation during the course of selection offers several advantages. Correlated responses to selection which appear late in selection may be verified by use of a cross-sectional experimental design to take a "snapshot" of the gradually developing response. After attainment of the selection limit, a generation may be chosen retrospectively which represents the best compromise between maximizing response and minimizing inbreeding irrelevant to the selected trait. Estimates of changes in gene frequencies could be derived from molecular biological analyses. An example of such an experiment in progress employing embryos from the COLD and HOT selected mouse lines is discussed.

Animals↗