Search

The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%-72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%-77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%-16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).

Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.

Alcohol dependence symptoms and consumption measures were examined for stability and heritability. Data were collected from 12,045 individuals (5376 twin pairs, 1293 single twins) aged 19 to 90 years in telephone interviews conducted in three collection phases. Phases 1 and 2 were independent samples, but Phase 3 targeted families of smokers and drinkers from the Phase 1 and 2 samples. The stability of dependence symptoms and consumption was examined for 1158 individuals interviewed in both Phases 1 and 3 (mean interval = 11.0 years). For 1818 individuals interviewed in Phases 2 and 3 (mean interval = 5.5 years) the stability of consumption was examined. Heritability was examined for each collection phase and retest samples from the selected Phase 3 collection. The measures examined were a dependence score, based on DSM-IIIR and DSM-IV criteria for substance dependence, and a quantity x frequency measure. Measures were moderately stable, with test-retest correlations ranging from .58 to .61 for dependence and from .55 to .64 for consumption. However, the pattern of changes over time for dependence suggested that the measure may more strongly reflect recent than lifetime experience. Similar to previous findings, heritabilities ranged from .42 to .51 for dependence and from .31 to .51 for consumption. Consumption was significantly less heritable in the younger Phase 2 cohort (23-39 years) compared to the older Phase 1 cohort (28-90 years).

It is difficult to study the genetic basis of psychological function/dysfunction due to its etiological complexity. Instead, we studied a biological marker, EEG power, which is associated with various psychological phenotypes and is closer to gene function. Previous studies have consistently demonstrated high heritability of EEG band power, but less is known about how common or specific genes influence each power band. For 519 adolescent twin pairs, spectral powers were calculated for delta, theta, alpha, and beta bands at bilateral occipital and frontal sites. All four bands were entered into a multivariate genetic model, with occipital and frontal sites modelled separately. Variance was decomposed into additive (A) and dominant (D) genetic factors, and common (C) and unique (E) environmental factors. Band heritabilities were higher at occipital (0.75-0.86) than frontal sites (0.46-0.80). Both common and specific genetic factors influenced the bands, with common genetic and specific genetic factors having more influence in the occipital and frontal regions, respectively. Non-additive genetic effects on beta power and a common environment effect on delta, theta, and alpha powers were observed in the frontal region.

A range of environmental risk factors, with childbirth the most notable, have been associated with the development of pelvic organ prolapse and urinary incontinence. However, indications of genetic influence (positive family histories, ethnic differences) have prompted research into the heritability of measures of pelvic organ descent and joint mobility, which have also been associated with prolapse and incontinence. Genes appear to influence about half of the variation in these measures and, furthermore, the pelvic organ measures are associated with elbow hyperextension at a phenotypic level (r approximately .2). We examined these measures in young, nulligravid women to determine if their association is due to a common genetic source. Data were collected from 178 Caucasian female co-twins and non-twin sisters, 50 of whom returned to be retested, which allowed reliability to be estimated and unreliable variance to be isolated in the multivariate analyses. Structural equation modeling was used to estimate genetic associations between latent elbow and bladder mobility factors for which heritabilities were estimated to be 0.80 and 0.64 respectively. The association between these factors appeared to be mediated by common genes (genetic r = .48, non-shared environmental r = -.06), with genes influencing latent elbow mobility accounting for 14% of the variation in latent bladder mobility. We speculate that genes influencing connective tissue structure may underlie this association.

Objectives: Breast-fed C-allele carriers of the rs single nucleotide polymorphism in the fatty acyl desaturase 2 ("FADS2") gene have been reported to show a 6.4 to 7 IQ point advantage over formula-fed C-allele carriers, with no effect of breast-feeding in GG carriers. An Australian sample was examined to determine if an interaction between breast-feeding and the rs174575 single nucleotide polymorphism had any effect on IQ. Method: This hypothesis was tested in more than 700 families of adolescent twins assessed for IQ and breast-feeding, birth weight, and "FADS2" polymorphisms, and parental socioeconomic status and education, and maternal "FADS2" status. Results: No significant evidence for a moderating effect on IQ of rs174575 C-carrier status and breast-feeding was found, and there no effects of maternal "FADS2" status on offspring IQ. In addition, no main effects of any "FADS2" polymorphisms on IQ were found when the genotype was kept as two-homozygote and one-heterozygote categories and indeed no evidence for effects of breast-feeding on IQ scores after controlling for parental socioeconomic status and education. The investigation was extended to two additional "FADS2" polymorphisms (rs1535 and rs174583), but again, although these polymorphisms code alleles affecting fatty acid metabolism, no main or interaction effects were found on IQ. Conclusion: These results support the view that apparent effects of breast-feeding on IQ reflect differential likelihood of breast-feeding as a function of parental education and did not support the predicted interaction effect of "FADS2" and breast-feeding on IQ. (Contains 6 tables and 1 figure.)

Study Objectives: To investigate the influence of genetic and environmental factors on sleep-wake behaviors across adolescence. Methods: Four hundred and ninety-five participants (aged 9-17; 55% females), including 93 monozygotic and 117 dizygotic twin pairs, and 75 unmatched twins, wore an accelerometry device and completed a sleep diary for 2 weeks. Results: Individual differences in sleep onset, wake time, and sleep midpoint were influenced by both additive genetic (44%-50% of total variance) and shared environmental (31%-42%) factors, with a predominant genetic influence for sleep duration (62%) and restorative sleep (43%). When stratified into younger (aged 9-14) and older (aged 16-17) subsamples, genetic sources were more prominent in older adolescents. The moderate correlation between sleep duration and midpoint (rP = -.43, rG = .54) was attributable to a common genetic source. Sleep-wake behaviors on school and nonschool nights were correlated (rP = .44-.72) and influenced by the same genetic and unique environmental factors. Genetic sources specific to night-type were also identified, for all behaviors except restorative sleep. Conclusions: There were strong genetic influences on sleep-wake phenotypes, particularly on sleep timing, in adolescence. Moreover, there may be common genetic influences underlying both sleep and circadian rhythms. The differences in sleep-wake behaviors on school and nonschool nights could be attributable to genetic factors involved in reactivity to environmental context. [ABSTRACT FROM AUTHOR]

Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h2) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan ( N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444-4458, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent's non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children's attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent's PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring - therefore acting via the parenting environment - was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual's own genetic inheritance and are mediated by parental socioeconomic competence. [ABSTRACT FROM AUTHOR]

Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism (r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables. [ABSTRACT FROM PUBLISHER]

Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge. [ABSTRACT FROM PUBLISHER]

The goal of the current study was to examine whether genetic and environmental influences on an important risk factor for disordered eating, weight and shape concern, remained stable over adolescence. This stability was assessed in 2 ways: whether new sources of latent variance were introduced over development and whether the magnitude of variance contributing to the risk factor changed. We examined an 8-item WSC subscale derived from the Eating Disorder Examination (EDE) using telephone interviews with female adolescents. From 3 waves of data collected from female-female same-sex twin pairs from the Australian Twin Registry, a subset of the data (which included 351 pairs at Wave 1) was used to examine 3 age cohorts: 12 to 13, 13 to 15, and 14 to 16 years. The best-fitting model contained genetic and environmental influences, both shared and nonshared. Biometrie model fitting indicated that nonshared environmental influences were largely specific to each age cohort, and results suggested that latent shared environmental and genetic influences that were influential at 12 to 13 years continued to contribute to subsequent age cohorts, with independent sources of both emerging at ages 13 to 15. The magnitude of all 3 latent influences could be constrained to be the same across adolescence. Ages 13 to 15 were indicated as a time of risk for the development of high levels of WSC, given that most specific environmental risk factors were significant at this time (e.g., peer teasing about weight, adverse life events), and indications of the emergence of new sources of latent genetic and environmental variance over this period. [ABSTRACT FROM AUTHOR]

There has been almost no overlap between behavior genetics and consumer behavior research, despite each field's importance in understanding society. In particular, both have neglected to study genetic influences on consumer adoption and usage of new technologies — even technologies as important as the mobile phone, now used by 5.8 out of 7.0 billion people on earth. To start filling this gap, we analyzed self-reported mobile phone use, intelligence, and personality traits in two samples of Australian teenaged twins (mean ages 14.2 and 15.6 years), totaling 1,036 individuals. ACE modeling using Mx software showed substantial heritabilities for how often teens make voice calls (.60 and .34 in samples 1 and 2, respectively) and for how often they send text messages (.53 and. 50). Shared family environment – including neighborhood, social class, parental education, and parental income (i.e., the generosity of calling plans that parents can afford for their teens) — had much weaker effects. Multivariate modeling based on cross-twin, cross-trait correlations showed negative genetic correlations between talking/texting frequency and intelligence (around –.17), and positive genetic correlations between talking/texting frequency and extraversion (about .20 to .40). Our results have implications for assessing the risks of mobile phone use such as radiofrequency field (RF) exposure and driving accidents, for studying adoption and use of other emerging technologies, for understanding the genetic architecture of the cognitive and personality traits that predict consumer behavior, and for challenging the common assumption that consumer behavior is shaped entirely by culture, media, and family environment. [ABSTRACT FROM PUBLISHER]

Binocular rivalry occurs when conflicting images are presented in corresponding locations of the two eyes. Perception alternates between the images at a rate that is relatively stable within individuals but that varies widely between individuals. The determinants of this variation are unknown. In addition, slow binocular rivalry has been demonstrated in bipolar disorder, a psychiatric condition with high heritability. The present study therefore examined whether there is a genetic contribution to individual variation in binocular rivalry rate. We employed the twin method and studied both monozygotic (MZ) twins (n = 128 pairs) who are genetically identical, and dizygotic (DZ) twins (n = 220 pairs) who share roughly half their genes. MZ and DZ twin correlations for binocular rivalry rate were 0.51 and 0.19, respectively. The best-fitting genetic model showed 52% of the variance in binocular rivalry rate was accounted for by additive genetic factors. In contrast, nonshared environmental influences accounted for 18% of the variance, with the remainder attributed to measurement error. This study therefore demonstrates a substantial genetic contribution to individual variation in binocular rivalry rate. The results support the vigorous pursuit of genetic and molecular studies of binocular rivalry and further characterization of slow binocular rivalry as an endophenotype for bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: The P3(00) event-related potential is an index of processing capacity (P3 amplitude) and stimulus evaluation (P3 latency) as well as a phenotypic marker of various forms of psychopathology where P3 abnormalities have been reported. Methods: A genome-wide linkage scan of 400–761 autosomal markers, at an average spacing of 5–10 centimorgans (cM), was completed in 647 twins/siblings (306 families mostly comprising dizygotic twins), mean age 16.3, range 15.4–20.1 years, for whom P3 amplitude and latency data were available. Results: Significant linkage for P3 amplitude was observed on chromosome 7q for the central recording site (logarithm-of-odds [LOD] = 3.88, p = .00002) and in the same region for both frontal (LOD = 2.19, p = .0015) and parietal (LOD = 1.67, p = .0053) sites, with multivariate analysis also identifying linkage in this region (LOD = 2.14, p = .0017). Suggestive linkage was also identified on 6p (LODmax = 2.49) and 12q (LODmax = 2.24), with other promising regions identified on 9q (LODmax = 2.14) and 10p (LODmax = 2.18). Less striking were the results for P3 latency; LOD > 1.5 were found on chromosomes 1q, 9q, 10q, 12q, and 19p. Conclusions: This is a first step in the identification of genes for normal variation in the P3. Loci identified here for P3 amplitude suggest the possible importance of neurodevelopmental genes in addition to those influencing neurotransmitters, fitting with the evidence that P3 amplitude is sensitive to diverse types of brain abnormalities. [Copyright &y& Elsevier]

Abstract: Brain-derived neurotrophic factor (BDNF) plays a key role in learning and memory, but its effects on the fiber architecture of the living brain are unknown. We genotyped 455 healthy adult twins and their non-twin siblings (188 males/267 females; age: 23.7±2.1years, mean±SD) and scanned them with high angular resolution diffusion tensor imaging (DTI), to assess how the BDNF Val66Met polymorphism affects white matter microstructure. By applying genetic association analysis to every 3D point in the brain images, we found that the Val-BDNF genetic variant was associated with lower white matter integrity in the splenium of the corpus callosum, left optic radiation, inferior fronto-occipital fasciculus, and superior corona radiata. Normal BDNF variation influenced the association between subjects'' performance intellectual ability (as measured by Object Assembly subtest) and fiber integrity (as measured by fractional anisotropy; FA) in the callosal splenium, and pons. BDNF gene may affect the intellectual performance by modulating the white matter development. This combination of genetic association analysis and large-scale diffusion imaging directly relates a specific gene to the fiber microstructure of the living brain and to human intelligence. [Copyright &y& Elsevier]

Background: Previous research has reported a significant genetic correlation between heaviness of alcohol consumption and alcohol dependence (AD), but this association might be driven by the influence of AD on consumption rather than the reverse. We test the genetic overlap between AD symptoms and a heaviness of consumption measure among individuals who do not have AD. A high genetic correlation between these measures would suggest that a continuous measure of consumption may have a useful role in the discovery of genes contributing to dependence risk. Methods: Factor analysis of five alcohol use measures was used to create a measure of heaviness of alcohol consumption. Quantitative genetic analyses of interview data from the 1989 Australian Twin Panel (n = 6257 individuals; M = 29.9 years) assessed the genetic overlap between heaviness of consumption, DSM-IV AD symptoms, DSM-IV AD symptom clustering, and DSM-IV alcohol abuse. Results: Genetic influences accounted for 30%–51% of the variance in the alcohol measures and genetic correlations were .90 or higher for all measures, with the correlation between consumption and dependence symptoms among nondependent individuals estimated at .97 (95% confidence interval: .80–1.00). Conclusions: Heaviness of consumption and AD symptoms have a high degree of genetic overlap even among nondependent individuals in the general population, implying that genetic influences on dependence risk in the general population are acting to a considerable degree through heaviness of use and that quantitative measures of consumption will likely have a useful role in the identification of genes contributing to AD. [Copyright &y& Elsevier]