Behavior Genetics最新文献

The environment is an important influence in the development of human behaviours and health outcomes. However, one of the most consistent findings from behavioural genetic studies is that most environmental influences are not shared between members of the same family. A compelling way of investigating these non-shared environmental influences is by using a monozygotic (MZ) twin differences design. Quantitative MZ differences studies have uncovered systematic non-shared environmental factors, i.e., those acting according to a general pattern in a population, for many traits, but may be omitting idiosyncratic or distinctive factors and mechanisms. Qualitative MZ differences design provides an alternative. In this study design, identical twins discordant on an outcome are interviewed in depth about the origins and context of their discordance, providing an insight into distinctive lived experiences. We conducted a systematic review examining the results and methodological features of studies using qualitative data collection and analyses to investigate differences in identical twins' experiences and outcomes. We applied a narrative synthesis. We identified seven studies, covering a range of phenotypes (e.g., anxiety or smoking) and participants (from children to older adults), which found a wide range of themes related to twins' discordance. A major theme arising from the narrative synthesis was the role of personality and individual traits, e.g., confidence or sexual orientation, in explaining MZ twins' discordant experiences and outcomes. Non-shared environmental factors are at least partly idiosyncratic and are therefore suitable for exploration with a qualitative research design, ideally in parallel with quantitative twin research in mixed-method research projects or programmes.

This study examined whether adolescent depressive and anxiety symptoms were differentially associated with alcohol use behaviors, and how these associations were explained by genetic, shared, and nonshared environmental influences. Participants were from the Nonshared Environment and Adolescent Development project of same-sex twin/sibling pairs from 720 families. Twin/sibling depressive and anxiety symptoms were measured by self-report at Time 1 (M_age = 13.71 years, range = 9-18 years). Alcohol initiation and alcohol use severity were measured by self-report three years after Time 1 (age range = 12-21 years). Phenotypic Cholesky models were used to estimate the variance of depressive symptoms and the unique variance of anxiety symptoms (independent of depressive symptoms), and how these variances were associated with alcohol initiation and alcohol use severity. Biometric Cholesky models then estimated contributions of genetic, shared and nonshared environmental influences to these variances and covariances. Antisocial behaviors were included in all analyses to account for their associations with depressive symptoms, anxiety symptoms and alcohol use behaviors. Analyses were conducted using the full, the younger half, and the older half of the sample to explore age differences in all associations. Depressive or anxiety symptoms were not associated with alcohol use behaviors after controlling for variance shared with antisocial behaviors, although age-specific analyses suggested some potential effects to explore in future studies for late adolescence. To conclude, longitudinal associations between depressive or anxiety symptoms and alcohol use behaviors during adolescence were mainly driven by the general psychopathology factor shared between internalizing and externalizing problems.

We aimed to understand the long-term impact of negative life events on epigenetic aging in 1783 adults from the Netherlands Twin Register, analyzing five epigenetic biomarkers (Hannum, Horvath, PhenoAge, GrimAge, DunedinPACE) and a series of negative life events, including victimization and economic hardship. In population-level analyses, associations between a higher number of negative life events (particularly financial adversities, sexual crimes, and job loss) were seen for the GrimAge biomarker. The association between the number of negative life events and financial problems and epigenetic age acceleration measured by the GrimAge biomarker persisted after adjusting for BMI, smoking, and white blood cell counts. In monozygotic twin pairs discordant for negative life events (263 pairs) the associations were diminished, indicating that the population associations may be confounded by shared familial (genetic and environmental) factors. These findings underscore the intricate link between environmental stressors and biological aging, stressing the need for comprehensive studies considering both genetic and environmental influences.

Diverse tests of cognitive abilities correlate about 0.30 phenotypically and about 0.60 genetically. Their phenotypic overlap defines general cognitive ability (g), driven largely by genetic overlap. Consequently, much of our understanding of the genetic landscape of specific cognitive tests likely reflects g rather than the tests themselves. Removing this g-associated genetic variance will sharpen research on cognitive tests. Here, we use Genomic Structural Equation Modelling (Genomic SEM) to remove shared genetic variance among 12 diverse cognitive tests that capture verbal and nonverbal cognitive domains. We applied Genomic SEM to summary statistics from the largest genome-wide association studies of verbal tests (GenLang Consortium, five tests) and largely nonverbal tests (UK Biobank, seven tests) to chart the genetic landscape of the 12 tests independent of g as compared to uncorrected cognitive tests. We found that SNP heritabilities were nearly as high for the tests corrected for g as uncorrected: the average SNP heritability was 0.16 (SE = 0.02) for the uncorrected tests and 0.13 (SE = 0.02) for the tests corrected for g. Despite this, the genetic landscape of the cognitive tests transformed after controlling for genomic g. The matrix of positive genetic correlations for the cognitive tests (average 0.45) disappeared after g-correction, and some strong negative correlations emerged; for instance, Memory and Word (-0.72), Fluid and Symbol (-0.72), and Tower and Spelling (-0.79). The summary statistics for these g-corrected cognitive tests can be used by researchers to create polygenic scores that focus on the specificity of the tests.

Previous research has supported the use of latent variables as the gold-standard in measuring executive function. However, for logistical reasons genome-wide association studies (GWAS) of executive function have largely eschewed latent variables in favour of singular task measures. As low correlations have traditionally been found between individual executive function (EF) tests, it is unclear whether these GWAS have truly been measuring the same construct. In this study, we addressed this question by performing a factor analysis on summary statistics from eleven GWAS of EF taken from five studies, using GenomicSEM. Models demonstrated a bifactor structure consistent with previous research, with factors capturing common EF and working memory- specific variance. Furthermore, the GWAS performed on this model identified 20 new genomic risk loci for common EF and 4 for working memory reaching genome-wide significance beyond what was found in the constituent GWAS, together resulting in 29 newly mapped EF genes. These results help to clarify the underlying genetic structure of EF and support the idea that EF GWAS are capable of measuring genetic variance related to latent EF constructs even when not using factor scores. Furthermore, they demonstrate that GenomicSEM can combine GWAS with divergent and non-ideal measures of the same phenotype to improve statistical power.

Breastfeeding is hypothesised to benefit child health and cognitive functioning by providing long-chain polyunsaturated fatty acids, which are essential for brain development. In 2007, Caspi et al. found evidence in two cohorts for an interaction between genetic variation in the FADS2 gene (a gene involved in fatty acid metabolism) and breastfeeding on IQ. However, subsequent studies have provided mixed evidence for the existence of an interaction. We investigated the relationship between genetic variation in the FADS2 region, breastfeeding, and their interaction in up to 335,650 individuals from the UK Biobank. We tested for the interaction over a range of cognitive functioning tests, as well as educational attainment and other traits thought to be influenced by breastfeeding, including cardiometabolic traits, number of offspring, and atopic allergy. FADS2 alleles associated with an increase in docosahexaenoic acid in blood serum (the C allele of rs174575) were associated with decreased verbal-numerical reasoning ( $p=2.28\times {10}^{-5}$ ) and triglycerides ( $p=1.40\times {10}^{-41}$ ), increased number of offspring ( $p=3.40\times {10}^{-5}$ ), total cholesterol ( $p=5.28\times {10}^{-36}$ ), HDL ( $p=1.42\times {10}^{-51}$ ), and LDL cholesterol ( $p=1.46\times {10}^{-21}$ ). We observed no evidence of an interaction in any of the traits, regardless of the modelling strategy on any cognitive or non-cognitive traits. We postulate that the previous positive findings are likely to be spurious, perhaps due to lack of appropriate control for latent population structure.

This paper provides an overview of the most recent assessment, collected in early midlife, of the FinnTwin12 cohort, a population-based study of Finnish twins born in 1983-1987. The twins were invited to complete an online survey assessing a range of variables, including physical and mental health, alcohol use and problems, other substance use, and early midlife environments (e.g., parenthood). In total, 2,085 individuals (~ 40% of the original sample) completed the survey (551 complete twin pairs, 58.7% female, 37.3% monozygotic, M_age = 37.2 years, SD = 1.47 years, age range = 34-39 years). Individuals who participated were more likely to be female, monozygotic, and have higher parental education and less hyperactivity/impulsivity and aggression at age 12 when compared to individuals who were invited but did not participate. Parental alcohol misuse and the twins' alcohol use and misuse at age 14 were not related to study retention. Alcohol misuse in early midlife was positively associated with nicotine dependence, lifetime use of cannabis and other drugs, trauma exposure, and depressive symptoms, and negatively associated with physical health and having biological children. These new data expand upon the wealth of measures collected as part of previous assessments, expanding the scope of work on the etiology and correlates of alcohol misuse within a longitudinal, genetically-informed framework. In addition to these new survey measures, we are planning an in-person assessment to collect physiological measurements and conduct additional in-depth phenotyping on a subset of twins who have been more intensively studied over the years.

Tattooing has become increasingly common in recent decades, yet little is known regarding factors that influence tattoo behavior. Sources of influence will be important, for instance in aiding studies of long-term health effects. From the population-based Danish Twin Tattoo Cohort established in 2021, the study included 9,173 randomly selected twins born 1920-2004. Among these were 4,790 (52%) responders to a questionnaire on tattooing and lifestyle factors. There were 55% females, 22% were monozygotic twins, and the median age was 51 years. Shared influence of tattooing over time was assessed by comparing monozygotic and dizygotic twin pairs. Responders were population representative on sex, age, and lifestyle factors. The cumulative incidence of being tattooed before age 25 years increased markedly from 6% (95% CI: 4-7%) for males and 0% (0-1%) for females born in 1925-1960 to 30% (25-35%) for males and 41% (37-46%) for females born in 1981-2004. Tattooing was over twice as common among ever smokers compared to never smokers born in 1981-2004 (average smoking effect at age 25 years: 36% (29-43%)). The likelihood of a twin getting tattooed if the co-twin is tattooed, was 2.0 (1.4-2.6) and 1.8 (1.5-2.2) times higher, for monozygotic and dizygotic twins, respectively. The findings indicate that variation in the likelihood of becoming tattooed is primarily explained by shared environmental factors 65% (35-95%), and that genetic influences explained little of this variation. This study demonstrates that strong environmental exposures shared by twin siblings irrespective of degree of genetic relatedness drive the choice for getting tattooed. We conclude that tattooing is a cultural group clustering phenomenon that goes beyond genetically oriented behavioral characteristics.

Social behavior is a common though variable trait across animal species. How much of the variation in social behavior is due to biological common mechanisms across animal species is unknown. In this study we examined to what extent human genetic variation in sociability is affected by pathways shared with Caenorhabditis elegans and whether any conserved sociability-linked genes show enhanced levels of essential functions and interactivity. We found inconsistent evidence of increased conservation with more thorough analyses resulting in no evidence of increased conservation of human sociability-linked genes. Conserved genes were highly interactive compared to nonconserved and random genes, while only a limited number of genetic interactions were found to be conserved. No evidence was found for enrichment of social phenotypes in C. elegans orthologs of human sociability-linked genes while evidence for associations with essential functions were limited. The activin A receptor type 2A (ACVR2A) gene appears to play a role in social behavior in both humans and C. elegans, making it an interesting gene for further study.

Artificial selection yielded four replicate high runner (HR) lines of mice that reached apparent selection limits (~ threefold increase in wheel revolutions per day vs. four control lines), despite maintenance of additive genetic variance. After 68 generations, we used animal models to test for changes in additive-genetic variances and covariance of the two measured components (average speed and duration) of running distance. We also attempted to break the selection limit by crossing two HR lines, then continuing directional selection on this hybrid line and on the two parental lines for nine generations. The genetic correlation between speed and duration was positive in the base population, but evolved to be negative in the two parental HR lines. Although heritability for both speed and duration (but not distance) increased in the hybrid line, their genetic correlation remained negative. Hybrid F₁ mice from generation 68 parents showed heterosis for running distance, which was lost in subsequent generations, and the hybrid line did not exceed the limit. Both male and female hybrids ran faster than parental lines for most generations, but running duration was intermediate or reduced, reflecting their negative genetic correlation. The evolved genetic trade-off between speed and duration may explain the inability for the hybrid line to break the selection limit for distance run, despite renewed additive genetic variance for at least one of its component traits.