Showing papers in "Behavior Genetics in 2017"
TL;DR: The goal of the current manuscript is to outline a general method for calculating power in twin studies, and to provide functions to allow researchers to easily conduct power analyses for a range of common twin models.
Abstract: Power is a ubiquitous, though often overlooked, component of any statistical analyses. Almost every funding agency and institutional review board requires that some sort of power analysis is conducted prior to data collection. While there are several excellent on line power calculators for independent observations, twin studies pose unique challenges that are not incorporated into these algorithms. The goal of the current manuscript is to outline a general method for calculating power in twin studies, and to provide functions to allow researchers to easily conduct power analyses for a range of common twin models. Several scenarios are discussed to demonstrate the importance of various factors that influence the power within the classical twin design and to serve as examples for the provided functions.
80 citations
TL;DR: The results suggest that the level of grooming behavior may be related to the expression pattern of vital honey bee genes, and Neurexin-1, in particular, might be useful as a bio-marker for behavioral traits in bees.
Abstract: Honey bee (Apis mellifera) grooming behavior is an important mechanism of resistance against the parasitic mite Varroa destructor. This research was conducted to study associations between grooming behavior and the expression of selected immune, neural, detoxification, developmental and health-related genes. Individual bees tested in a laboratory assay for various levels of grooming behavior in response to V. destructor were also analyzed for gene expression. Intense groomers (IG) were most efficient in that they needed significantly less time to start grooming and fewer grooming attempts to successfully remove mites from their bodies than did light groomers (LG). In addition, the relative abundance of the neurexin-1 mRNA, was significantly higher in IG than in LG, no groomers (NG) or control (bees without mite). The abundance of poly U binding factor kd 68 and cytochrome p450 mRNAs were significantly higher in IG than in control bees. The abundance of hymenoptaecin mRNA was significantly higher in IG than in NG, but it was not different from that of control bees. The abundance of vitellogenin mRNA was not changed by grooming activity. However, the abundance of blue cheese mRNA was significantly reduced in IG compared to LG or NG, but not to control bees. Efficient removal of mites by IG correlated with different gene expression patterns in bees. These results suggest that the level of grooming behavior may be related to the expression pattern of vital honey bee genes. Neurexin-1, in particular, might be useful as a bio-marker for behavioral traits in bees.
36 citations
TL;DR: The findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression, and the direction of the association between AV PR1a genotype and extraversion ran counter to what one would expect if AVPR 1a was related to social behaviors.
Abstract: Polymorphisms of the arginine vasopressin receptor 1a (AVPR1a) gene have been linked to various measures related to human social behavior, including sibling conflict and agreeableness. In chimpanzees, AVPR1a polymorphisms have been associated with traits important for social interactions, including sociability, joint attention, dominance, conscientiousness, and hierarchical personality dimensions named low alpha/stability, disinhibition, and negative emotionality/low dominance. We examined associations between AVPR1a and six personality domains and hierarchical personality dimensions in 129 chimpanzees (Pan troglodytes) living in Japan or in a sanctuary in Guinea. We fit three linear and three animal models. The first model included genotype, the second included sex and genotype, and the third included genotype, sex, and sex × genotype. All personality phenotypes were heritable. Chimpanzees possessing the long form of the allele were higher in conscientiousness, but only in models that did not include the other predictors; however, additional analyses suggested that this may have been a consequence of study design. In animal models that included sex and sex × genotype, chimpanzees homozygous for the short form of the allele were higher in extraversion. Taken with the findings of previous studies of chimpanzees and humans, the findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression. The direction of the association between AVPR1a genotype and extraversion ran counter to what one would expect if AVPR1a was related to social behaviors. These results help us further understand the genetic basis of personality in chimpanzees.
30 citations
TL;DR: In both the cross-sectional and longitudinal analyses, testing the direct causal effect of ADHD on educational achievement, while controlling for genetic and environmental factors, revealed an association between ADHD symptoms and educational achievement independent of genetic andEnvironmental pleiotropy.
Abstract: Attention Deficit Hyperactivity Disorder (ADHD) and educational achievement are negatively associated in children. Here we test the hypothesis that there is a direct causal effect of ADHD on educational achievement. The causal effect is tested in a genetically sensitive design to exclude the possibility of confounding by a third factor (e.g. genetic pleiotropy) and by comparing educational achievement and secondary school career in children with ADHD who take or do not take methylphenidate. Data on ADHD symptoms, educational achievement and methylphenidate usage were available in a primary school sample of ~10,000 12-year-old twins from the Netherlands Twin Register. A substantial group also had longitudinal data at ages 7–12 years. ADHD symptoms were cross-sectionally and longitudinally, associated with lower educational achievement at age 12. More ADHD symptoms predicted a lower-level future secondary school career at age 14–16. In both the cross-sectional and longitudinal analyses, testing the direct causal effect of ADHD on educational achievement, while controlling for genetic and environmental factors, revealed an association between ADHD symptoms and educational achievement independent of genetic and environmental pleiotropy. These findings were confirmed in MZ twin intra-pair differences models, twins with more ADHD symptoms scored lower on educational achievement than their co-twins. Furthermore, children with ADHD medication, scored significantly higher on the educational achievement test than children with ADHD who did not use medication. Taken together, the results are consistent with a direct causal effect of ADHD on educational achievement.
29 citations
TL;DR: A method to test the association of a SNP with multiple phenotypes or a latent construct on a genome-wide basis using a diagonally weighted least squares (DWLS) estimator for four common SEMs: a one-factor model, aOne-factor residuals models, a two-Factor model, and a latent growth model.
Abstract: Improving the accuracy of phenotyping through the use of advanced psychometric tools will increase the power to find significant associations with genetic variants and expand the range of possible hypotheses that can be tested on a genome-wide scale. Multivariate methods, such as structural equation modeling (SEM), are valuable in the phenotypic analysis of psychiatric and substance use phenotypes, but these methods have not been integrated into standard genome-wide association analyses because fitting a SEM at each single nucleotide polymorphism (SNP) along the genome was hitherto considered to be too computationally demanding. By developing a method that can efficiently fit SEMs, it is possible to expand the set of models that can be tested. This is particularly necessary in psychiatric and behavioral genetics, where the statistical methods are often handicapped by phenotypes with large components of stochastic variance. Due to the enormous amount of data that genome-wide scans produce, the statistical methods used to analyze the data are relatively elementary and do not directly correspond with the rich theoretical development, and lack the potential to test more complex hypotheses about the measurement of, and interaction between, comorbid traits. In this paper, we present a method to test the association of a SNP with multiple phenotypes or a latent construct on a genome-wide basis using a diagonally weighted least squares (DWLS) estimator for four common SEMs: a one-factor model, a one-factor residuals model, a two-factor model, and a latent growth model. We demonstrate that the DWLS parameters and p-values strongly correspond with the more traditional full information maximum likelihood parameters and p-values. We also present the timing of simulations and power analyses and a comparison with and existing multivariate GWAS software package.
28 citations
TL;DR: Assessment of executive functioning in PKU patients during childhood and in adulthood showed that patients with phenylalanine <360 µmol/L in childhood and phenyl Alanine from age 13 onwards had better cognitive flexibility and executive motor control than those who had phenylAlanine ≥360 ±L throughout life, supporting the notion that phenylalinine should be below the recommended upper treatment target during childhood for better outcome in adulthood.
Abstract: Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean age 10.4 years, SD = 2.0) and again in adulthood (T2, mean age 25.8 years, SD = 2.3). At T2 additional assessments of EF in daily life and mental health were performed. Childhood (i.e. 0-12 years) blood phenylalanine was significantly related to cognitive flexibility, executive motor control, EF in daily life and mental health in adulthood (i.e. at T2). Patients with a greater increase in phenylalanine levels after the age of 12 performed more poorly on EF-tasks at T2. Group-based analyses showed that patients with phenylalanine <360 µmol/L in childhood and phenylalanine ≥360 µmol/L from age 13 onwards (n = 11) had better cognitive flexibility and executive motor control than those who had phenylalanine ≥360 µmol/L throughout life (n = 7), supporting the notion that phenylalanine should be below the recommended upper treatment target of 360 µmol/L during childhood for better outcome in adulthood. Despite some results indicating additional influence of phenylalanine levels between 13 and 17 years of age, evidence for a continued influence of phenylalanine levels after childhood on adult outcomes was largely lacking. This may be explained by the fact that the patients in the present study had relatively low phenylalanine levels during childhood (mean: 330 µmol/L, range: 219-581 µmol/L) and thereafter (mean Index of Dietary Control at T2: 464 µmol/L, range: 276-743 µmol/L), which may have buffered against transitory periods of poor metabolic control during adolescence and early adulthood.
26 citations
TL;DR: The findings support the role of genetics on reading comprehension, and a small significant role of shared environmental influences, and suggest that the interpretation of how genes and environments influence reading comprehension should reflect aspects of study and sample.
Abstract: Numerous twin studies have examined the genetic and environmental etiology of reading comprehension, though it is likely that etiological estimates are influenced by unidentified sample conditions (e.g. Tucker-Drob and Bates, Psychol Sci:0956797615612727, 2015). The purpose of this meta-analysis was to average the etiological influences of reading comprehension and to explore the potential moderators influencing these estimates. Results revealed an average heritability estimate of h2 = 0.59, with significant variation in estimates across studies, suggesting potential moderation. Moderation results indicated publication year, grade level, project, zygosity methods, and response type moderated heritability estimates. The average shared environmental estimate was c2 = 0.16, with publication year, grade and zygosity methods acting as significant moderators. These findings support the role of genetics on reading comprehension, and a small significant role of shared environmental influences. The results suggest that our interpretation of how genes and environments influence reading comprehension should reflect aspects of study and sample.
26 citations
TL;DR: A small but statistically significant causal effect of age at menarche on time spent in education is demonstrated: a 1 year increase in age atMenarche is associated with 0.14 years (53 days) increase in time spend in education, and this positive causal effect is confirmed in sensitivity analyses.
Abstract: Menarche signifies the primary event in female puberty and is associated with changes in self-identity. It is not clear whether earlier puberty causes girls to spend less time in education. Observational studies on this topic are likely to be affected by confounding environmental factors. The Mendelian randomization (MR) approach addresses these issues by using genetic variants (such as single nucleotide polymorphisms, SNPs) as proxies for the risk factor of interest. We use this technique to explore whether there is a causal effect of age at menarche on time spent in education. Instruments and SNP-age at menarche estimates are identified from a Genome Wide Association Study (GWAS) meta-analysis of 182,416 women of European descent. The effects of instruments on time spent in education are estimated using a GWAS meta-analysis of 118,443 women performed by the Social Science Genetic Association Consortium (SSGAC). In our main analysis, we demonstrate a small but statistically significant causal effect of age at menarche on time spent in education: a 1 year increase in age at menarche is associated with 0.14 years (53 days) increase in time spent in education (95% CI 0.10–0.21 years, p = 3.5 × 10−8). The causal effect is confirmed in sensitivity analyses. In identifying this positive causal effect of age at menarche on time spent in education, we offer further insight into the social effects of puberty in girls.
25 citations
TL;DR: The nature of the sibling relationship in dyads of varying genetic relatedness was compared, employing a behavioural genetic design to estimate the contribution that genes and the environment have on this familial bond, and evidence of twin-specific environmental influence was found.
Abstract: We compared the nature of the sibling relationship in dyads of varying genetic relatedness, employing a behavioural genetic design to estimate the contribution that genes and the environment have on this familial bond Two samples were used—the Sisters and Brothers Study consisted of 173 families with two target non-twin children (mean ages = 742 and 522 years respectively); and the Twins, Family and Behaviour study included 234 families with two target twin children (mean age = 470 years) Mothers and fathers reported on their children’s relationship with each other, via a postal questionnaire (the Sisters and Brothers Study) or a telephone interview (the Twins, Family and Behaviour study) Contrary to expectations, no mean level differences emerged when monozygotic twin pairs, dizygotic twin pairs, and non-twin pairs were compared on their sibling relationship quality Behavioural genetic analyses also revealed that the sibling bond was modestly to moderately influenced by the genetic propensities of the children within the dyad, and moderately to substantially influenced by the shared environment common to both siblings In addition, for sibling negativity, we found evidence of twin-specific environmental influence—dizygotic twins showed more reciprocity than did non-twins Our findings have repercussions for the broader application of results from future twin-based investigations
23 citations
TL;DR: Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD, and both fit substantially better than the Correlated Liabilities model.
Abstract: Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935–953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high.
23 citations
TL;DR: Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas there is no evidence that this is also the case for NSSI.
Abstract: Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age = 42.4 years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p = 0.008, explained variance ranging from 0.10 to 0.16 %) and, less consistently, in suicide attempts (lowest p = 0.04, explained variance ranging from 0.12 to 0.23 %). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI.
TL;DR: The hippocampus and cerebellum reduced sizes that were seen in all the strains indicate that trisomy 21 is not only a hippocampus syndrome but that it results from abnormal interactions between the two structures.
Abstract: We hypothesize that the trisomy 21 (Down syndrome) is the additive and interactive outcome of the triple copy of different regions of HSA21. Because of the small number of patients with partial trisomy 21, we addressed the question in the Mouse in which three chromosomal regions located on MMU10, MMU17 and MMU16 carries almost all the HSA21 homologs. Male mice from four segmental trisomic strains covering the D21S17-ETS2 (syntenic to MMU16) were examined with an exhaustive battery of cognitive tests, motor tasks and MRI and compared with TS65Dn that encompasses D21S17-ETS2. None of the four strains gather all the impairments (measured by the effect size) of TS65Dn strain. The 152F7 strain was close to TS65Dn for motor behavior and reference memory and the three other strains 230E8, 141G6 and 285E6 for working memory. Episodic memory was impaired only in strain 285E6. The hippocampus and cerebellum reduced sizes that were seen in all the strains indicate that trisomy 21 is not only a hippocampus syndrome but that it results from abnormal interactions between the two structures.
TL;DR: Five species of whale with matrilineal social systems have remarkably low levels of mitochondrial DNA diversity and culture, bottlenecks and selection, as well as their interactions, operating between- or within-ecotypes, may have reduced their mitochondrial diversity.
Abstract: Five species of whale with matrilineal social systems (daughters remain with mothers) have remarkably low levels of mitochondrial DNA diversity. Non-heritable matriline-level demography could reduce genetic diversity but the required conditions are not consistent with the natural histories of the matrilineal whales. The diversity of nuclear microsatellites is little reduced in the matrilineal whales arguing against bottlenecks. Selective sweeps of the mitochondrial genome are feasible causes but it is not clear why these only occurred in the matrilineal species. Cultural hitchhiking (cultural selection reducing diversity at neutral genetic loci transmitted in parallel to the culture) is supported in sperm whales which possess suitable matrilineal socio-cultural groups (coda clans). Killer whales are delineated into ecotypes which likely originated culturally. Culture, bottlenecks and selection, as well as their interactions, operating between- or within-ecotypes, may have reduced their mitochondrial diversity. The societies, cultures and genetics of false killer and two pilot whale species are insufficiently known to assess drivers of low mitochondrial diversity.
TL;DR: The genetic correlations indicated that the most efficient birds fed more frequently and were less fearful, and four genes involved in fear reactions were identified in the QTL for tonic immobility on GGA1.
Abstract: The genetic relationships between behavior and digestive efficiency were studied in 860 chickens from a cross between two lines divergently selected on digestive efficiency. At 2 weeks of age each chick was video-recorded in the home pen to characterize general activity and feeding behavior. Tonic immobility and open-field tests were also carried out individually to evaluate emotional reactivity (i.e. the propensity to express fear responses). Digestive efficiency was measured at 3 weeks. Genetic parameters of behavior traits were estimated. Birds were genotyped on 3379 SNP markers to detect QTLs. Heritabilities of behavioral traits were low, apart from tonic immobility (0.17–0.18) and maximum meal length (0.14). The genetic correlations indicated that the most efficient birds fed more frequently and were less fearful. We detected 14 QTL (9 for feeding behavior, 3 for tonic immobility, 2 for frequency of lying). Nine of them co-localized with QTL for efficiency, anatomy of the digestive tract, feed intake or microbiota composition. Four genes involved in fear reactions were identified in the QTL for tonic immobility on GGA1.
TL;DR: The findings support the validity of ASPD as a unidimensional diagnostic construct because both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable.
Abstract: Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI 40-67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct.
TL;DR: While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males, which contribute to the observed DDt-R mating costs.
Abstract: Understanding the evolution and spread of insecticide resistance requires knowing the relative fitness of resistant organisms. In the absence of insecticides, resistance is predicted to be costly. The Drosophila melanogaster DDT resistance allele (DDT-R) is associated with a male mating cost. This could be because resistant males are generally smaller, but DDT-R may also alter courtship behaviours. Here we tested for body size and courtship effects of DDT-R on mating success in competitive and non-competitive mating trials respectively. We also assessed relative aggression in resistant and susceptible males because aggression can also influence mating success. While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males. These differences contribute to the observed DDT-R mating costs. Additionally, these pleiotropic effects of DDT-R are consistent with the history and spread of resistance alleles in nature.
TL;DR: Polygenic risk scores for autism, attention-deficit/hyperactive disorder, bipolar disorder, major depression, and schizophrenia are derived using genome-wide data from the Psychiatric Genomics Consortium as discovery samples, and there is no evidence for larger effect sizes for EFs as endophenotypes for psychiatric disorders.
Abstract: Executive functions (EFs) have been proposed as an endophenotype for psychopathology because EF deficits are associated with most psychiatric disorders. To examine this hypothesis, we derived polygenic risk scores for autism, attention-deficit/hyperactive disorder (ADHD), bipolar disorder, major depression (MDD), and schizophrenia, using genome-wide data from the Psychiatric Genomics Consortium as discovery samples. We then examined the relationships between these polygenic risk scores and three separable EF components measured with a latent variable model. We also examined the relationship between genetic risk for ADHD and MDD and their respective symptom counts and lifetime diagnoses. We found no evidence for larger effect sizes for EFs as endophenotypes for psychiatric disorders. However, larger sample sizes will be important in examining this relationship further.
TL;DR: The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition.
Abstract: Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2081 genes and 3526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93 %) affected the mean and/or variance of food consumption.
TL;DR: This is the first study to account for measurement error while examining the heritability of CU traits, furthering the understanding of psychopathy in children.
Abstract: Callous-unemotional (CU) traits comprise the core symptoms of psychopathy, yet no study has estimated the heritability of CU traits in a community sample of children using an instrument designed solely to assess CU traits. The current study uses data from 339 twin pairs aged 9-14 to examine the reliability and heritability of the parent-report Inventory of Callous-unemotional Traits (ICU) at two assessments approximately 3 weeks apart. Time-specific measurement error was taken into account to obtain a more accurate estimate of the heritability reflecting the latent liability to CU traits. Test-retest reliability was 0.84 and heritability at visit 1 was 39%. The heritability of the latent liability to CU traits was 47%. This latent liability contributed 79% of the variance in ICU score at visit 1 and visit 2. This is the first study to account for measurement error while examining the heritability of CU traits, furthering our understanding of psychopathy in children.
TL;DR: This article examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCRL rats, in the delay discounting task.
Abstract: Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of “impulsive” SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.
TL;DR: The results suggest that metamorphosis can change trade-offs between behavioral traits and suggest that the negative correlation between tonic immobility and walking is decoupled across life stages from larva to adult.
Abstract: Many animal behaviors have a genetic base, and behavioral traits often correlate with one another. In this study, we tested for a behavioral correlation between tonic immobility and walking distance in the larval and adult stages independently of two holometabolous insects. We confirmed a negative correlation of traits between strains in adults of both the species; however, we did not find it in larvae of either species. This suggests that the negative correlation between tonic immobility and walking is decoupled across life stages from larva to adult. In contrast, previous studies have reported that phenotypic correlations between behavioral traits are maintained from larvae to adults in hemimetabolous insects. In addition, our present results differ from previous results with holometabolous insects. Therefore, our results suggest that metamorphosis can change trade-offs between behavioral traits.
TL;DR: A large F2 population including 537 individuals by cross-breeding tame and aggressive fox strains was constructed and genetic mapping identified eight unique significant and suggestive QTL suggesting that different QTL are involved in regulation of behaviors exhibited in different behavioral contexts.
Abstract: Individuals involved in a social interaction exhibit different behavioral traits that, in combination, form the individual’s behavioral responses. Selectively bred strains of silver foxes (Vulpes vulpes) demonstrate markedly different behaviors in their response to humans. To identify the genetic basis of these behavioral differences we constructed a large F2 population including 537 individuals by cross-breeding tame and aggressive fox strains. 98 fox behavioral traits were recorded during social interaction with a human experimenter in a standard four-step test. Patterns of fox behaviors during the test were evaluated using principal component (PC) analysis. Genetic mapping identified eight unique significant and suggestive QTL. Mapping results for the PC phenotypes from different test steps showed little overlap suggesting that different QTL are involved in regulation of behaviors exhibited in different behavioral contexts. Many individual behavioral traits mapped to the same genomic regions as PC phenotypes. This provides additional information about specific behaviors regulated by these loci. Further, three pairs of epistatic loci were also identified for PC phenotypes suggesting more complex genetic architecture of the behavioral differences between the two strains than what has previously been observed.
TL;DR: Multivariate models indicate that family formation, demographic, and psychological phenotypes leave no residual genetic variance in completed fertility in either dataset, largely consistent across U.S. and U.K. sociocultural contexts.
Abstract: In modern societies, individual differences in completed fertility are linked with genotypic differences between individuals. Explaining the heritability of completed fertility has been inconclusive, with alternative explanations centering on family formation timing, pursuit of education, or other psychological traits. We use the twin subsample from the Midlife Development in the United States study and the TwinsUK study to examine these issues. In total, 2606 adult twin pairs reported on their completed fertility, age at first birth and marriage, level of education, Big Five personality traits, and cognitive ability. Quantitative genetic Cholesky models were used to partition the variance in completed fertility into genetic and environmental variance that is shared with other phenotypes and residual variance. Genetic influences on completed fertility are strongly related to family formation timing and less strongly, but significantly, with psychological traits. Multivariate models indicate that family formation, demographic, and psychological phenotypes leave no residual genetic variance in completed fertility in either dataset. Results are largely consistent across U.S. and U.K. sociocultural contexts.
TL;DR: A two-tiered strategy is employed, a proof of concept study, to explore the feasibility of behavioral screens in zebrafish, finding significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed.
Abstract: The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens. We generated mutant lines using transposon-based insertional mutagenesis, allowing us to bias mutant selection with target genes expressed within the brain. Furthermore, we employed an efficient and fast behavioral pre-selection in which we investigated the locomotory response of 5-day post-fertilization old larval fish to hyperosmotic shock. Based on this assay, we selected five lines for our lower throughput secondary adult behavioral screen. The latter screen utilized tests in which computer animated image presentation and video-tracking-based automated quantification of behavior allowed us to compare heterozygous zebrafish with their wild-type siblings on their responses to a variety of stimuli. We found significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed, including changes in response to social or fear inducing stimuli, to handling and novelty, or in habituation to novelty. We discuss the pros and cons of behavioral phenotyping and of the use of different forward genetic methods in biomedical research with zebrafish.
TL;DR: The aim of this twin study was to quantify the rater common and rater specific contributions to the variation in children’s behavioral problems, and estimated the heritability of maternal and paternal ratings of the Child Behavior Checklist 6–18 empirical emotional and behavioral problem scales in a large sample of 12,310 7-year old Dutch twin pairs.
Abstract: In studies of child psychopathology, phenotypes of interest are often obtained by parental ratings When behavioral ratings are obtained in the context of a twin study, this allows for the decomposition of the phenotypic variance, into a genetic and a non-genetic part If a phenotype is assessed by a single rater, heritability is based on the child’s behavior as expressed in the presence of that particular rater, whereas heritability based on assessments by multiple raters allows for the estimation of the heritability of the phenotype based on rater agreement, as well as the heritability of the rater specific view of the behavior The aim of this twin study was to quantify the rater common and rater specific contributions to the variation in children’s behavioral problems We estimated the heritability of maternal and paternal ratings of the Child Behavior Checklist (CBCL) 6–18 empirical emotional and behavioral problem scales in a large sample of 12,310 7-year old Dutch twin pairs Between 30 and 59% of variation in the part of the phenotype parents agree upon was explained by genetic effects Common environmental effects that make children in the same family similar explained less variance, ranging between 0 and 32% For unique views of their children’s behavioral problems, heritability ranged between 0 and 20% for maternal and between 0 and 22% for paternal views Between 7 and 24% of the variance was accounted for by common environmental factors specific to mother and father’s views The proportion of rater shared and rater specific heritability can be translated into genetic correlations between parental views and inform the design and interpretation of results of molecular genetic studies Genetic correlations were nearly or above 07 for all CBCL based psychopathology scales Such large genetic correlations suggest two practical guidelines for genome-wide association studies (GWAS): when studies have collected data from either fathers or mothers, the shared genetic aetiology in parental ratings indicates that is possible to analyze paternal and maternal assessments in a single GWAS or meta-analysis Secondly, if a study has collected information from both parents, a gain in statistical power may be realized in GWAS by the simultaneous analysis of the data
TL;DR: The present genetically sensitive multi-group study analyzed data from 223 twin pairs and 222 biological core families to estimate possible genetic and environmental sources of individual differences in implicit and explicit self-esteem and affect.
Abstract: In today's world, researchers frequently utilize indirect measures of implicit (i.e., automatic, spontaneous) evaluations. The results of several studies have supported the usefulness of these measures in predicting behavior, as compared to utilizing direct measures of explicit (i.e., purposeful, deliberate) evaluations. A current, under-debate issue concerns the origin of these implicit evaluations. The present genetically sensitive multi-group study analyzed data from 223 twin pairs and 222 biological core families to estimate possible genetic and environmental sources of individual differences in implicit and explicit self-esteem and affect. The results show that implicit self-esteem and affect maintain a substantial genetic basis, but demonstrate little influence from the shared environment by siblings (e.g., shared familial socialization in childhood). A bivariate analysis found that implicit and explicit evaluations of the same construct share a common genetic core which aligns with the motivation and opportunity as determinants (MODE) model.
TL;DR: The results imply that two distinct processes influence adolescent AU between the ages of 15–25, while unique environmental effects are more cumulative.
Abstract: The precise nature of how genetic and environmental risk factors influence changes in alcohol use (AU) over time has not yet been investigated. Therefore, the aim of the present study is to examine the nature of longitudinal changes in these risk factors to AU from mid-adolescence through young adulthood. Using a large sample of male twins, we compared five developmental models that each makes different predictions regarding the longitudinal changes in genetic and environmental risks for AU. The best-fitting model indicated that genetic influences were consistent with a gradual growth in the liability to AU, whereas unique environmental risk factors were consistent with an accumulation of risks across time. These results imply that two distinct processes influence adolescent AU between the ages of 15–25. Genetic effects influence baseline levels of AU and rates of change across time, while unique environmental effects are more cumulative.
TL;DR: Both genetic and non-shared environmental influences are important for behavioral disinhibition (Q-Score) and planning (Test Age) in twins drawn from the RFAB.
Abstract: The Porteus Maze Test (PMT) provides measures of planning and behavioral disinhibition. The PMT was administered to 941 twins during Wave 1 (9–10 years) and 320 twins during Wave 2 (11–13 years). Participants were drawn from the University of Southern California Risk Factors for Antisocial Behavior Study (RFAB). Heritability of behavioral disinhibition, determined by PMT Q-Score, were 33% at Wave 1 and 52% at Wave 2. For planning, determined by Test Age, heritability was 53% at Wave 1; at Wave 2, the non-shared environment was important in boys, whereas genetic influences were important in girls. Both indices were modestly stable (r = 0.52; r = 0.37). A common genetic factor influenced both indices, respectively, at the two time points, with no ‘new’ genetic variance at Wave 2; the non-shared environment was time-specific. Thus, both genetic and non-shared environmental influences are important for behavioral disinhibition (Q-Score) and planning (Test Age).
TL;DR: Post-ET between-strain differences in avoidance acquisition, context-conditioned freezing and novelty-induced self-grooming are conserved, suggesting that the pre-/post-natal environment may have influenced these co-segregated traits at G1, though further selection pressure along the subsequent generations rescues the typical strain-related differences.
Abstract: The Roman high- (RHA-I) and low-avoidance (RLA-I) rat strains are bi-directionally bred for their good versus non-acquisition of two-way active avoidance, respectively. They have recently been re-derived through embryo transfer (ET) to Sprague-Dawley females to generate specific pathogen free (SPF) RHA-I/RLA-I rats. Offspring were phenotyped at generations 1 (G1, born from Sprague-Dawley females), 3 and 5 (G3 and G5, born from RHA-I and RLA-I from G2-G4, respectively), and compared with generation 60 from our non-SPF colony. Phenotyping included two-way avoidance acquisition, context-conditioned fear, open-field behaviour, novelty-seeking, baseline startle, pre-pulse inhibition (PPI) and stress-induced increase in plasma corticosterone concentration. Post-ET between-strain differences in avoidance acquisition, context-conditioned freezing and novelty-induced self-grooming are conserved. Other behavioural traits (i.e. hole-board head-dipping, novel object exploration, open-field activity, startle, PPI) differentiate the strains at G3-G5 but not at G1, suggesting that the pre-/post-natal environment may have influenced these co-segregated traits at G1, though further selection pressure along the subsequent generations (G1-G5) rescues the typical strain-related differences.
TL;DR: The observed associations between polygenic reading and adult outcomes mostly remained, suggesting that the pathway from reading ability to social outcomes is not only via associated polygenic loads for general cognitive function and educational attainment.
Abstract: Impairments in reading and in language have negative consequences on life outcomes, but it is not known to what extent genetic effects influence this association. We constructed polygenic scores for difficulties with language and learning to read from genome-wide data in ~6,600 children, adolescents and young adults, and tested their association with health, socioeconomic outcomes and brain structure measures collected in adults (maximal N = 111,749). Polygenic risk of reading difficulties was associated with reduced income, educational attainment, self-rated health and verbal-numerical reasoning (p < 0.00055). Polygenic risk of language difficulties predicted income (p = 0.0005). The small effect sizes ranged 0.01–0.03 of a standard deviation, but these will increase as genetic studies for reading ability get larger. Polygenic scores for childhood cognitive ability and educational attainment were correlated with polygenic scores of reading and language (up to 0.09 and 0.05, respectively). But when they were included in the prediction models, the observed associations between polygenic reading and adult outcomes mostly remained. This suggests that the pathway from reading ability to social outcomes is not only via associated polygenic loads for general cognitive function and educational attainment. The presence of non-overlapping genetic effect is indicated by the genetic correlations of around 0.40 (childhood intelligence) and 0.70 (educational attainment) with reading ability. Mendelian randomization approaches will be important to dissociate any causal and moderating effects of reading and related traits on social outcomes.