Suchergebnisse

AbstractIt is widely recognized that dizygotic twinning (DZT) runs in families, but estimates of heritability from twin and family data are remarkably scarce and vary considerably. Here, we traced seven large, sometimes historical, multigeneration pedigrees from West Africans, fin de siècle French Jews, Canadians (two pedigrees), and the French royal family, in which twin births were recorded. We estimated heritability of twinning (of all types) as zygosity information was not available, diluting the true DZT heritability by a third or so. The estimates in the range 8−20% are remarkably consistent across time (8−19 generations) and ethnicities and also consistent with twin and family estimates.

SummaryResearch has established that genetic differences among people explain a greater or smaller proportion of the variation in life outcomes in different environmental conditions. This review evaluates the results of recent educationally relevant behavioural genetic studies and meta-analyses in the context of recent trends in income and wealth distribution. The pattern of results suggests that inequality and social policies can have profound effects on the heritability of educational attainment and achievement in a population (Gene–Gini interplay). For example, heritability is generally higher at greater equality levels, suggesting that inequality stifles the expression of educationally relevant genetic propensities. The review concludes with a discussion of the mechanisms of Gene–Gini interplay and what the findings mean for efforts to optimize education for all people.

Structural brain measures are employed as endophenotypes in the search for schizophrenia susceptibility genes. We analyzed two independent structural imaging datasets with voxel-based morphometry and with source-based morphometry, a multivariate, independent components analysis, to determine the stability and heritability of regional gray matter concentration abnormalities in schizophrenia. The samples comprised 209 and 102 patients with schizophrenia and 208 and 96 healthy volunteers, respectively. The second sample additionally included non-ill siblings of participants with and without schizophrenia. A standard voxel-based analysis showed reproducible regional gray matter deficits in the affected participants compared with unrelated, unaffected controls in both datasets: patients showed significant gray matter concentration deficits in cortical frontal, temporal, and insular lobes. Source-based morphometry (SBM) was applied to the gray matter images of the entire sample to determine the effects of diagnosis on networks of covarying structures. The SBM analysis extracted 24 significant sets of covarying regions (components). Four of these components showed significantly lower gray matter concentrations in patients (p < .05). We determined the familiality of the observed SBM components based on 66 sibling pairs (25 discordant for schizophrenia). Two components, one including the medial frontal, insular, inferior frontal, and temporal lobes, and the other including the posterior occipital lobe, showed significant familiality (p < .05). We conclude that structural brain deficits in schizophrenia are replicable, and that SBM can extract unique familial and likely heritable components. SBM provides a useful data reduction technique that can provide measures that may serve as endophenotypes for schizophrenia.

Familial factors have previously been implicated in the etiology of fatigue, of which a significant proportion is likely attributable to genetic influences. However, family studies have primarily focused on chronic fatigue syndrome, while univariate twin studies have investigated broader fatigue phenotypes. The results for similar fatigue phenotypes vary between studies, particularly with regard to sex-specific contributions to the heritability of the traits. Therefore, the current study aims to investigate the familiality and sex-specific effects of fatigue experienced over the past few weeks in an older Australian population of 660 monozygotic (MZ) twin pairs, 190 MZ singleton twins, 593 dizygotic (DZ) twin pairs, and 365 DZ singleton twins. Higher risks for fatigue were observed in MZ compared to DZ co-twins of probands with fatigue. Univariate heritability analyses indicated fatigue has a significant genetic component, with a heritability (h2) estimate of 40%. Sex-specific effects did not significantly contribute to the heritability of fatigue, with similar estimates for males (h2= 41%, 95% CI [18, 62]) and females (h2= 40%, 95% CI [27, 52]). These results indicate that fatigue experienced over the past few weeks has a familial contribution, with additive genetic factors playing an important role in its etiology.

AbstractType 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18–67 years and free from diabetes at baseline during 1997–2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.

SummaryThe study focused on the extent to which the general factor of intelligence g and heritability coefficients of the subtests of an IQ battery correlate. Modest to strong positive correlations were found in five studies from Western countries and six studies from a Japanese meta-analysis. The results for Russian twins were compared with those of the Western and Japanese studies. Data from 402 twins aged 13 and 296 twins aged 16 showed correlations of r=−0.45 and r=−0.60, respectively. It is concluded that the two data points are clearly not in line with established findings. It may be that the link between g loadings and heritabilities is more complex than previously thought.

Twin studies described a strongly heritable component of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. However, findings varied considerably between studies. In addition, ADHD presents with a high rate of comorbid disorders and associated psychopathology. Therefore, this literature review reports findings from population-based twin studies regarding the influence of subtypes, assessment instruments, rater effects, sex differences, and comorbidity rates on ADHD heritability estimates. In addition, genetic effects on the persistence of ADHD are discussed. By reviewing relevant factors influencing heritability estimates more homogeneous subtypes relevant for molecular genetic studies can be elicited. A systematic search of population-based twin studies in ADHD was performed, using the databases PubMed and PsycInfo. Results of family studies were added in case insufficient or contradictory findings were obtained in twin studies. Heritability estimates were strongly influenced by rater effects and assessment instruments. Inattentive and hyperactive–impulsive symptoms were likely influenced by common as well as specific genetic risk factors. Besides persistent ADHD, ADHD accompanied by symptoms of conduct or antisocial personality disorder might be another strongly genetically determined subtype, however, family environmental risk factors have also been established for this pattern of comorbidity.

AbstractHeritability of age at menarche (AAM) in African populations remains largely unknown. A question on AAM was given to 1803 [454 monozygotic (MZ), 823 same-sex dizygotic (DZ), and 526 female members of opposite sex] adolescent twins attending public schools in Lagos State, Nigeria. The age range of the sample was 12–18 years, with a mean (SD) of 14.57 (±1.70) years. The data included 905 missing cases consisting of those who had not experienced menarche and did not recall AAM. Missing values were imputed using the Expectation-Maximization algorithm. Kaplan–Meier analysis based on the imputed data yielded 13.23 years [95% CI [13.18, 13.28] for the mean and 13.00 years [95% CI [12.96, 13.04] for the median of AAM. Twin correlation and model-fitting analyses were performed on the basis of those who reported AAM (MZ = 82 complete pairs and 38 cotwin missing cases; DZ = 157 complete pairs and 99 cotwin missing cases). Maximum likelihood MZ and DZ twin correlations for AAM were .63 (95% CI [.48, .74]) and .33 (95% CI [.19, .45]) respectively. Model-fitting analyses indicated that 58% (95% CI [46, 67]) of the variance of AAM was associated with additive genetic influences with the remaining variance, 42% (33−54) being due to nonshared environmental influences including measurement error. The heritability estimate found in this study was within the range of those found in Asian and Western twin samples.

The monocyte–lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-family population. Data were obtained in 9,501 individuals from the Netherlands Twin Register. We used regression analyses to determine the effects of age, sex, smoking, and body mass index (BMI) on MLR and its subcomponents. Data on twins, siblings and parents (N = 7,513) were analyzed by genetic structural equation modeling to establish heritability and genome wide single nucleotide polymorphism (SNP) data from a genotyped subsample (N = 5,892) and used to estimate heritability explained by SNPs. SNP and phenotype data were also analyzed in a genome-wide association study to identify the genes involved in MLR. Linkage disequilibrium (LD) score regression and expression quantitative trait loci (eQTL) analyses were performed to further explore the genetic findings. Results showed that age, sex, and age × sex interaction effects were present for MLR and its subcomponents. Variation in MLR was not related to BMI, but smoking was positively associated with MLR. Heritability was estimated at 40% for MLR, 58% for monocyte, and 58% for lymphocyte count. The Genome-wide association study (GWAS) identified a locus on ITGA4 that was associated with MLR and only marginally significantly associated with monocyte count. For monocyte count, additional genetic variants were identified on ITPR3, LPAP1, and IRF8. For lymphocyte count, GWAS provided no significant findings. Taking all measured SNPs together, their effects accounted for 13% of the heritability of MLR, while all known and identified genetic loci explained 1.3% of variation in MLR. eQTL analyses showed that these genetic variants were unlikely to be eQTLs. In conclusion, variation in MLR level in the general population is heritable and influenced by age, sex, and smoking. We identified gene variants in the ITGA4 gene associated with variation in MLR. The significant SNP-heritability indicates that more genetic variants are likely to be involved.

SummaryIntelligence was assessed using the Standard
Progressive Matrices in 316 MZ and 550 same-sex DZ
twins with a mean age of 10 years in Sudan.
Heritability was estimated at 0.172 and shared
environmental influences at 0.596.

We examined the genetic architecture of functional brain connectivity measures in resting state electroencephalographic (EEG) recordings. Previous studies in Dutch twins have suggested that genetic factors are a main source of variance in functional brain connectivity derived from EEG recordings. In addition, qualitative descriptors of the brain network derived from graph analysis — network clustering and average path length — are also heritable traits. Here we replicated previous findings for connectivity, quantified by the synchronization likelihood, and the graph theoretical parameters cluster coefficient and path length in an Australian sample of 16-year-old twins (879) and their siblings (93). Modeling of monozygotic and dizygotic twins and sibling resemblance indicated heritability estimates of the synchronization likelihood (27–74%) and cluster coefficient and path length in the alpha and theta band (40–44% and 23–40% respectively) and path length in the beta band frequency (41%). This corroborates synchronization likelihood and its graph theoretical derivatives cluster coefficient and path length as potential endophenotypes for behavioral traits and neurological disorders.