Unique Genetic Influences Research Articles

Overlapping genetic and child-specific nonshared environmental influences on listening comprehension, reading motivation, and reading comprehension

This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects.

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort.

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3,689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample of ages 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis (GCTA) to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (e.g. reading ability, h2g=0.43, p=4e-06; emotion identification, h2g=0.36, p=1e-05; verbal memory, h2g=0.24, p=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (e.g. language reasoning and spatial reasoning, r(g)=0.72, p=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities.

Genetic complexity of episodic memory: a twin approach to studies of aging.

Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if "memory is memory" and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR). An advantage of the twin method is that it can estimate the extent to which latent genetic influences are shared or independent across different measures before knowing which specific genes are involved. The best-fitting model was a higher order common pathways model with a heritable higher order general episodic memory factor and three test-specific subfactors. More importantly, substantial genetic variance was accounted for by genetic influences that were specific to the latent LM and VR subfactors (28% and 30%, respectively) and independent of the general factor. Such unique genetic influences could partially account for replication failures. Moreover, if different genes influence different memory phenotypes, they could well have different age-related trajectories. This approach represents an important step toward providing critical information for all types of genetically informative studies of aging and memory.

Shared and unique genetic and environmental influences on aging-related changes in multiple cognitive abilities.

Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying multivariate growth curve models to longitudinal data from 857 individuals from the Swedish Adoption/Twin Study of Aging, who had been measured on 11 cognitive variables representative of verbal, spatial, memory, and processing speed abilities up to 5 times over up to 16 years between ages 50 and 96 years. Between ages 50 and 65 years scores on different tests changed relatively independently of one another, and there was little evidence for strong underlying dimensions of change. In contrast, over the period between 65 and 96 years of age, there were strong interrelations among rates of change both within and across domains. During this age period, variability in rates of change were, on average, 52% domain-general, 8% domain-specific, and 39% test-specific. Quantitative genetic decomposition indicated that 29% of individual differences in a global domain-general dimension of cognitive changes during this age period were attributable to genetic influences, but some domain-specific genetic influences were also evident, even after accounting for domain-general contributions. These findings are consistent with a balanced global and domain-specific account of the genetics of cognitive aging.

Examining the etiological associations among higher-order temperament dimensions

A multivariate independent pathway model was used to examine the shared and unique genetic and environmental influences of Positive Affect (PA), Negative Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age=10.07, SD=1.74). There were common genetic influences and nonshared environmental influences shared across all three temperament dimensions and shared environmental influences in common to NA and EC. There were also significant independent genetic influences unique to PA and NA and significant independent shared environmental influences unique to PA. This study demonstrates that there are genetic and environmental influences that affect the covariance among temperament dimensions as well as unique genetic and environmental influences that influence the dimensions independently.

Supplemental Material for Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

Supplemental Material for Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

Focus on systemic lupus erythematosus in Indigenous Australians: towards a better understanding of autoimmune diseases

The incidence and prevalence of autoimmune diseases such as rheumatoid arthritis, primary Sjögren syndrome, scleroderma and systemic lupus erythematosus (SLE) varies with geography and ethnicity. For example, SLE is reported to be more common in populations such as African-Caribbeans and Indigenous Australians (IA). As well as socio-economic status, variation in severity of disease may also show ethnic variability. The initial presentation of SLE in IA, in the context of a unique genetic background and distinctive environmental influences, is often florid with a recurring spectrum of clinical phenotypes. These clinical observations suggest a unique pathway for autoimmunity pathogenesis in this population. For instance, the high prevalence of bacterial infections in IA, particularly group A streptococcus, may be a potential explanation not only for increased incidence and prevalence of SLE but also the commonly florid acute disease presentation and propensity for rapidly progressive end organ threatening disease. This article will review the state of research in autoimmune disease of IA, consider key findings related to autoimmune disease in this population and propose a model potentially to explain the involvement of innate immunity and chronic infection in autoimmune disease pathogenesis. Ultimately, understanding of SLE at this level could affect management and result in personalised and targeted therapies to improve the health status of IA as well as better understanding of SLE pathogenesis per se.

A Behavioral Genetic Investigation of Weekend Drinking Among an Adult Sample

This study examined common and unique genetic and environmental influences on weekend drinking and weekday drinking reported by US male and female adult participants (mean age = 43.9). Data from 96 monozygotic and 82 dizygotic twin pairs were used to estimate bivariate biometric models of daily levels of weekend and weekday drinking volume. Weekend and weekday drinking volume scores were calculated from end-of-day reports of drinking across eight days. As expected, more drinking occurred during weekends. Biometric models provided evidence of significant additive genetic and nonshared environmental influences on both weekend and weekday drinking. Shared environmental influences were nonsignificant. Genetic influences accounted for a greater proportion of drinking variance during weekdays than weekends (0.36 compared to 0.17). However, these apparent differences in heritability—proportion of total variance accounted for by genetic variance—were due to increased nonshared environmental influences on weekend days, rather than greater genetic influences. The study's limitations are noted. Funded by National Institutes of Health/National Institute of Aging and John D. and Catherine T. MacArthur Foundation.

The role of gene–environment correlations and interactions in middle childhood depressive symptoms

Depression is known to be associated with a wide array of environmental factors. Such associations are due at least in part to genetic influences on both. This issue has been little explored with preadolescent children. Measures of family chaos and parenting style at age 9 and child depressive symptoms at age 12 were completed by 3,258 twin pairs from the Twins Early Development Study and their parents. Quantitative genetic modeling was used to explore common and unique genetic and environmental influences on both family environment and later depressive symptoms. Depressive symptoms at age 12 were significantly heritable. Moderate genetic effects influenced parenting style and family chaos at the age of 9, indicating gene-environment correlation. There were significant genetic correlations between family environment and depressive symptoms. There was some evidence of a Gene × Environment interaction, with stronger genetic effects on depressive symptoms for children with more suboptimal family environment. There was an Environment × Environment interaction, with effects of nonshared environment on depressive symptoms stronger for twins with more adverse parenting experiences. There is some evidence for gene-environment correlation between aspects of family environment in middle childhood and subsequent depressive symptoms. This suggests that one of the mechanisms by which genes lead to depressive symptoms may be by themselves influencing depressogenic environments.

Genetic architecture of the Delis-Kaplan executive function system Trail Making Test: Evidence for distinct genetic influences on executive function.

To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

Do leadership role occupancy and transformational leadership share the same genetic and environmental influences?

Using data collected from 107 pairs of identical and 89 pairs of fraternal female twins, this study examined the genetic and environmental associations between transformational leadership and leadership role occupancy. Results show that 78% of the covariance between the two leadership variables was attributable to overlapping genetic factors, while 22% of the covariance to overlapping environmental factors. In particular, 13% (2%) of the variance in leadership role occupancy was accounted for by the same genetic (environmental) factors related to transformational leadership. Unique sets of genetic and environmental variables, which are not associated with transformational leadership, explained 16% and 69% of the variance in leadership role occupancy, respectively. The results suggest that multiple manifestations of leadership (i.e., transformational leadership and leadership role occupancy) are differentially heritable. Although the association between these two variables is largely due to overlapping genetic rather than environmental factors, unique (i.e., non-overlapping) genetic and environmental influences still play an important role in impacting these leadership variables.

Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study

African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10−7≤P≤1.1*10−5) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10−6). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P<2.0*10−4) were in the beta variable region of the T-cell receptor gene (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans.

Neuroticism and self-reported somatic health: A twin study

Using a twin sample (N = 188; 53 monozygotic and 39 dizygotic twin pairs, and 4 single twins whose co-twin did not participate), this study sought (1) to estimate heritabilities of neuroticism and of somatic complaints rated on the basis of two different time frames (‘the last week’ vs. ‘in general’); (2) to estimate the genetic association between neuroticism and the complaints indices and (3) to examine to what extent somatic complaints are aetiologically distinct from neuroticism. Using models with common additive genetic (A) and individual-specific environmental (E) factors, the heritabilities for neuroticism and complaints ‘in general’ and during ‘the last week’ were 0.46 (0.20–0.65), 0.44 (0.22–0.62), and 0.45 (0.22–0.63), respectively. Nearly 60% of the phenotypic correlation between neuroticism and somatic complaints were accounted for by A. Furthermore, a substantial part of the variance in somatic complaints was due to unique genetic and individual-specific environmental influences unrelated to neuroticism. These results suggest that somatic complaints are moderately heritable and that a considerable portion of the covariance between neuroticism and complaints measures is due to genetic factors. Yet, the findings also suggest that these two attributes are distinct entities with overlapping, but not identical, underlying genetic and environmental influences.

Review of Attention-Deficit/Hyperactivity Disorder Comorbid with Oppositional Defiant Disorder

The aim of this paper was to conduct a practitioner review of attention-deficit/hyperactivity disorder (ADHD) co-occurring with oppositional defiant disorder (ODD) encompassing aetiological factors, associated factors, assessment, treatment and prognosis. ADHD and ODD have both shared and unique genetic influences. Persistence of ADHD and ODD in adolescence is linked with an increased risk of delinquent behaviour, substance dependence, anxiety, depression, and possibly bipolar disorder. The diagnostic work up for ADHD must include screening for ODD, which may be achieved through targeted questioning or the use of standard symptom checklists. Treatment requires management of the core symptoms of ADHD plus, in many cases, augmentation with other treatment to address the ODD. Mild cases may respond to behaviour management alone, or monotherapy with stimulant medication or atomoxetine. Moderate to severe cases usually require a combination of pharmacotherapy, which may include clonidine, and behaviour management. Severe or refractory cases may require the introduction of an atypical antipsychotic such as risperidone.

Exploring How Symptoms of Attention-Deficit/Hyperactivity Disorder Are Related to Reading and Mathematics Performance

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance.

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.

Shared and unique genetic and environmental influences on binge eating and night eating: A Swedish twin study

Shared and unique genetic and environmental influences on binge eating and night eating: A Swedish twin study

Shared and unique genetic and environmental influences on binge eating and night eating: A Swedish twin study

We applied twin methodology to female and male twin pairs to further understand the nature of the relation between two behaviors associated with eating disorders—binge eating (BE) and night eating (NE) in an effort to determine the extent of overlap of genetic and environmental factors influencing liability to these behaviors. We calculated heritability estimates for males and females for each behavior and applied bivariate twin modeling to the female data to estimate the genetic and environmental correlation between these two traits. Data on BE and NE were derived from the Swedish Twin study of Adults: Genes and Environment (STAGE) of the Swedish Twin Registry (STR; N = 11,604). Prevalence estimates revealed sex differences with females more likely to endorse BE and males more likely to endorse NE. In males, we were only able to estimate univariate heritabilities due to small sample sizes: The heritability for BE was 0.74 [95% CI = (0.36, 0.93)] and for NE was 0.44 [95% CI = (0.24, 0.61)]. The best fitting bivariate model for females included additive genetic and unique environmental factors as well as the genetic correlation between BE and NE. Heritability estimates were 0.70 [95% CI = (0.26, 0.77)] for BE and 0.35 [95% CI = (0.17, 0.52)] for NE. The genetic correlation, 0.66 [95% CI = (0.48, 0.96)] suggests considerable overlap in the genetic factors influencing liability to BE and NE. In females, there is considerable overlap in the genetic factors that contribute to these traits, but the incomplete overlap allows for the influence of independent genetic and environmental factors as well. BE and NE in females are therefore best conceptualized as related but not identical traits.

Twinning on the brain: The effect on neurodevelopmental outcomes

Twinning is currently considered a complex multifactorial trait. Few studies have explored how the unique genetic and environmental influences that create twinning affect phenotypes and outcomes. Previous data has shown that twins account for a significant proportion of preterm and low-birth-weight infants, who are at risk for long-term neurodevelopmental disabilities such as cerebral palsy and cognitive impairment. More recently, it has been postulated that even without these co-morbidities, twinning in and of itself may incur a neurodevelopmental disadvantage even among term newborns. The purpose of this review is to report primarily on neuromotor outcomes of twins compared to singletons. In addition, we describe specific environmental risk factors among twins which are associated with poorer outcomes. Several putative neurodevelopmental modulators are explored, including death of a co-twin, chorionicity, birth weight discordance, and twin-twin transfusion. By teasing out environmental influences that potentially influence neurocognitive outcomes, families can receive more specific counseling and developmental services can be provided to those twins at especially high risk.

Differential role of serotonergic polymorphisms in alcohol and heroin dependence

Background Twin studies suggest that genetic factors account for 40–60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence. Methods 165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. Results Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of −1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI) = 1.98 (1.13–3.45) and 1.92 (1.07–3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df) = 10.21 (4), p = 0.037). The association of −1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups. Conclusions Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.