Tuesday, June 11, 2019

Behavior Genetics

Genetics of Perceived Family Interaction From 12 to 17 Years of Age

Abstract

We analyzed how the effects of genetic and environmental factors on the perceptions of family interaction change from early to late adolescence. The data were collected by postal surveys on Finnish twins (N = 4808) at 12, 14 and 17 years of age and analyzed using genetic twin modeling. Additive genetic factors explained a modest share of the variation in perceived relational support (a2 = 0.30 in boys and 0.18 in girls) and relational tensions (a2 = 0.13 and 0.14, respectively) at 12 years of age, with the proportions becoming larger through 17 years of age (a2 = 0.53 in boys and 0.49 in girls for relational support; a2 = 0.35 in boys and 0.33 in girls for relational tensions). Simultaneously, the role of environment shared by co-twins decreased. These findings suggest that the associations between perceived family interaction and other factors in adulthood should be interpreted with caution, because they partly reflect genetic background, whereas in childhood, they may provide more reliable information on parental characteristics.



Half the Genetic Variance in Vitamin D Concentration is Shared with Skin Colour and Sun Exposure Genes

Abstract

This study assessed the heritability of 25 hydroxyvitamin D3 (25(OH)D3) in a large twin cohort and the shared effect of sun exposure and skin colour on 25(OH)D3 variance. Study participants included 1604 twin pairs and their siblings (n = 4020). Twin correlations for 25(OH)D3 concentration were rMZ=0.79 (584 pairs) and rDZ = 0.52 (1020 pairs) consistent with an average h2 = 0.50 throughout the year. Significant phenotypic and genetic seasonal fluctuation was observed in 25(OH)D3 concentrations with heritability decreasing during the winter (h2 = 0.37) compared to summer (h2 = 0.62). Skin colour (measured both ordinally and quantitatively) and self-reported sun exposure were found to significantly affect 25(OH)D3 concentration. Twins with olive/dark skin had significantly lower 25(OH)D3 concentrations than those with fair/pale skin and multivariate genetic analysis showed that approximately half of the total additive genetic variation in 25(OH)D3 results from genes whose primary influence is on skin colour and sun exposure. Additionally, 37% of the total variance was attributed to shared environmental effects on vitamin D, skin colour and sun exposure measures. These results support a moderate estimate of vitamin D heritability and suggest significant influence of season, skin colour and sun exposure on the genetic variance.



Significance of IL-6 Deficiency in Recognition Memory in Young Adult and Aged Mice

Abstract

Chronic peripheral elevation of interleukin 6 (IL-6) in humans is associated with cognitive deficits. 4- and 24-month-old IL-6-deficient C57BL/6J (IL-6KO) and reference wild-type (WT) mice were tested in an object recognition test. Discrimination ratios and recognition indexes were significantly lower in 4-month-old IL-6KO and in 24-month-old WT mice vs 4-month-old WT animals. Their discrimination ratios had negative values and recognition indexes were below 50% indicating inability to differentiate the novel from the familiar object after 1-hour delay. In 24-month-old IL-6KO mice recognition index reached 53.17% indicating that their recognition memory was not worsened with age in comparison with younger IL-6-deficient animals. Results of holeboard and elevated plus maze indicated that this effect was memory specific. Inborn IL-6 deficiency attenuated recognition memory in 4-month-old mice and did not altered recognition memory in aged animals. IL-6 signalling may constitute a target for development of the protection against memory disturbances connected with IL-6 overexpression.



Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects

Abstract

Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.



The Genetic and Environmental Etiology of Shyness Through Childhood

Abstract

The objective of this study was to examine the genetic and environmental contributions to shyness throughout the school-age period. Participants were 553 twin pairs from the ongoing prospective longitudinal Quebec Newborn Twin Study. Teacher-rated measures of shyness were collected at five time-points from age 6–12 years. On average, shyness was moderately stable over time (r = 0.23–0.33) and this stability was almost entirely accounted for by genetic factors. Genetic factors at age 6 accounted for 44% of individual differences and these early genetic factors also explained individual differences at all subsequent ages (6–22%). Non-shared environmental factors explained most of individual differences at single time-points (51–63%), and did not account for stability in shyness. Contributions of shared environment were not significant. Our results suggest that the stability in shyness is mostly accounted for by early and persistent genetic contributions.



Systematic Review of Polygenic Gene–Environment Interaction in Tobacco, Alcohol, and Cannabis Use

Abstract

Studies testing the effect of single genetic variants on substance use have had modest success. This paper reviewed 39 studies using polygenic measures to test interaction with any type of environmental exposure (G×E) in alcohol, tobacco, and cannabis use. Studies using haplotype combinations, sum scores of candidate-gene risk alleles, and polygenic scores (PS) were included. Overall study quality was moderate, with lower ratings for the polygenic methods in the haplotype and candidate-gene score studies. Heterogeneity in investigated environmental exposures, genetic factors, and outcomes was substantial. Most studies (N = 30) reported at least one significant G×E interaction, but overall evidence was weak. The majority (N = 26) found results in line with differential susceptibility and diathesis-stress frameworks. Future studies should pay more attention to methodological and statistical rigor, and focus on replication efforts. Additional work is needed before firm conclusions can be drawn about the importance of G×E in the etiology of substance use.



Cognitive Performance in Young APOE ε4 Carriers: A Latent Variable Approach for Assessing the Genotype–Phenotype Relationship

Abstract

The ε4 allele of the apolipoprotein (APOE) gene is a widely recognized genetic risk factor for developing Alzheimer's disease in older age. However, it is controversial whether there is a positive impact of the APOE ε4 allele on human cognitive performance in young adulthood, possibly representing a case of antagonistic pleiotropy. Here we explored associations of the APOE ε4 allele with cognitive ability in young adulthood. In contrast to previous studies, we used structural equation modeling that allows a multivariate measurement of the cognitive phenotype. Results based on four independent samples (N1 = 245; N2 = 300; N3 = 244; N4 = 206) overall revealed a complex effect of the APOE ε4 genotype on cognitive ability in young adulthood: Whereas the ε4 allele tends to be negatively associated with cognitive performance in individuals with lower education levels, there might be a weak positive association in persons with higher education—a finding that is partly in line with the antagonistic pleiotropy view on APOE and cognitive ability. The education-related findings support protective effects of environmental factors.



Correction to: A Genetic Investigation of the Well-Being Spectrum

In the original version of this article, unfortunately, in the acknowledgement section "National Institutes of Health (NIH, R37 AG033590‐08) to J Cacioppo" was omitted. This has been corrected by publishing this erratum.



Correction to: Behavioral Genetics and Attributions of Moral Responsibility

The original version of this article unfortunately contained a few mistakes in the Introduction section.



A Genetic Investigation of the Well-Being Spectrum

Abstract

The interrelations among well-being, neuroticism, and depression can be captured in a so-called well-being spectrum (3-phenotype well-being spectrum, 3-WBS). Several other human traits are likely linked to the 3-WBS. In the present study, we investigate how the 3-WBS can be expanded. First, we constructed polygenic risk scores for the 3-WBS and used this score to predict a series of traits that have been associated with well-being in the literature. We included information on loneliness, big five personality traits, self-rated health, and flourishing. The 3-WBS polygenic score predicted all the original 3-WBS traits and additionally loneliness, self-rated health, and extraversion (R2 between 0.62% and 1.58%). Next, using LD score regression, we calculated genetic correlations between the 3-WBS and the traits of interest. From all candidate traits, loneliness and self-rated health were found to have the strongest genetic correlations (rg = − 0.79, and rg= 0.64, respectively) with the 3-WBS. Lastly, we use Genomic SEM to investigate the factor structure of the proposed spectrum. The best model fit was obtained for a two-factor model including the 5-WBS traits, with two highly correlated factors representing the negative- and positive end of the spectrum. Based on these analyses we propose to include loneliness and self-rated health in the WBS and use a 5-phenotype well-being spectrum in future studies to gain more insight into the determinants of human well-being.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

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