Behavior Genetics最新文献

Asian residents frequently have a higher percentage of body fat in comparison to individuals with European ancestry, which increases their susceptibility to metabolic diseases. This study aimed to explore the familial resemblance patterns of different body adiposity indicators among 16,983 Tehranian adults. The intraclass correlation coefficients (ICC) of first-degree pairs were estimated to verify the family resemblance of the anthropometric and adiposity-related traits(ARTs) between family members and spouses. The family-based heritability of ARTs was estimated using the classical likelihood-based approach. Results were obtained based upon two scenarios: the first measurement scenario(FM), analysis of the individuals' ARTs in which they become ≥ 18 years for the first time, and the second scenario, which was based on the average of valid values of the ARTs for each individual(AM). There were 22,879 first-degree relative pairs (17,562 Parents/offspring and 5,137 siblings), 11,015 s-degree relative pairs, and 1,299 third-degree cousin pairs. The familial resemblance between sibling pairs of the same sex was significantly higher than those of other pairs, as for brother: brother pairs, ICC ranged between 19.6% (95%CI:0.118,0.274) for a body shape index(ABSI) to 35.6% (95%CI:0.280,0.432) for body mass index(BMI). Also, for sister: sister pairs, ICC varied from 19.4% (95%CI:0.116,0.272)(ABSI) to 36.6% (95%CI:0.280,0.432)(BMI). For spouses, ICC varied between 5.6% (95%CI:0.025,0.087) for waist-to-hip ratio(WHR) to 10.4% (95%CI:0.065,0.143) for waist circumference. Family-based heritability estimation ranged from 28% (SE = 0.026) for body adiposity index (BAI) to 43% (SE = 0.024) for BMI. The highest pairwise correlation between family members was shown to exist between siblings, and same-sex relative pairs have shown a relatively larger correlation than relative pairs with a different sex.

Whether education modifies genetic influences on cognition has not been fully explored, especially in non-European populations. Using the older adult cohort from the Taiwan Biobank of East Asian populations, this study aimed to investigate the modifying effect of education on the association of the apolipoprotein E (APOE) ε4 allele and polygenic scores (PGS) for Alzheimer's disease (PGS_AD), cognitive performance (PGS_CP), education attainment (PGS_EA), and schizophrenia (PGS_SCZ) with cognitive ability. Participants aged > 60 years were included in this cohort study. The Mini-Mental State Examination (MMSE) was used for cognitive assessment of 27,343 individuals at baseline (mean age: 63.57 years), and follow-up data were available for 6,273 participants. Linear regression models were employed to examine the association between genetic factors and baseline MMSE scores and MMSE decline and further stratified by education to test the modifying effect. The APOE ε4 allele, PGS_AD, PGS_CP, PGS_EA, and PGS_SCZ were associated with baseline MMSE but not MMSE decline. The positive effects of the PGS_CP and PGS_EA on baseline MMSE, and negative effect of the PGS_SCZ on baseline MMSE and MMSE decline were higher for individuals with lower education. This study demonstrated the transferability of European-derived PGSs to older community samples of East Asian populations. Education mitigates specific genetic effects on cognition, which supports and extends cognitive reserve theory. Promoting cognitive health in older adults by extending education is of importance, especially for populations with higher genetic predispositions and lower education attainment.

Despite significant advances in pre- and postnatal care over the last century, adverse pregnancy related events still occur frequently. We used Mendelian randomisation (MR) to investigate potential causal effects of the mother's and fetal blood proteome on pregnancy related outcomes including birthweight, placental weight, preeclampsia, and sporadic miscarriage. We generated a list of genetic instruments to act as proxies for plasma proteins by combining two recent large protein GWAS (4719 proteins N = 35,559 individuals; 4775 proteins N = 10,708 individuals). We identified 1724 proteins with valid cis-pQTLs for use as genetic instruments. We identified evidence for causal relationships (MR Bonferroni corrected p_Bonferroni < 2.90 × 10^-5) involving fetal effects and/or maternal effects on birthweight and preeclampsia. Increased levels of PSG7 and BCMA and decreased levels of VLCAD, INHBB, and PLCG1 in the fetal circulation were potentially causal for increased birthweight. Similarly, increased levels of LIMA1 and decreased levels of VLCAD, FBLN3, and galectin-4 in the maternal circulation were potentially causal for increased birthweight. Decreased levels of SERPINE2 and SIGLEC6 were potentially causal for increased risk of preeclampsia. We did not find any significant effects of proxied maternal or fetal proteins on placental weight or sporadic miscarriage, perhaps due to the smaller size of their GWAS meta-analyses. Our results implicate several proteins that may be involved in the aetiology of perinatal phenotypes that will need to be replicated in independent datasets.

Literacy is a significant predictor of important life outcomes, such as attained education and income (Ritchie and Bates in Psychol Sci 24(7):1301-1308, 2013. 10.1177/0956797612466268) yet difficulties in reading and spelling are common. Both genetic and environmental factors account for individual differences in reading and spelling abilities (Little et al. in Behav Genet 47:52-76, 2017. 10.1007/s10519-016-9810-6), but there is some evidence that genetic factors can be moderated by environmental factors, many of which relate to differences in socio-economic status (SES). Studies in the US indicate that the heritability of reading and spelling abilities is higher in higher SES environments (Hart et al. in J Child Psychol Psychiatry 54(10):1047-1055, 2013. 10.1111/jcpp.12083; Friend et al. in Psychol Sci 19(11), 2008. 10.1111/j.1467-9280.2008.02213.x). Because countries differ in terms of factors such as education access and social mobility, the genetics (or simply gene) x SES interaction may or may not be present in other populations. Here, we utilise summary statistics from a well-powered genome-wide association study on dyslexia (Doust et al. in Nat Genet 54:1621-1629, 2022. 10.1038/s41588-022-01192-y) to construct polygenic indices in two cohorts of children/adolescents in Australia (N = 1315) and the United Kingdom (N = 5461 at age 7; N = 4306 at age 16), and test whether the effect of measured genes on variation in reading ability is moderated by family SES. While polygenic indices and SES both showed statistically significant effects on reading and spelling performance, no interaction effect was found. These results are contrary to results of some twin studies in the United States that have found an interaction effect. Yet, these findings support the broader literature on gene x SES interaction that mostly report no such interaction in other cognitive traits outside the United States suggesting country differences in how strongly SES relates to education quality.

Amidst growing visibility of gender diversity, the aetiology of gender identity has become a subject of increasing public interest. Prompted by the growing public debate, we review here the extant twin literature regarding the origins of gender diversity. Literature was reviewed systematically, searching Medline, Embase and PubMed databases. Studies were deemed eligible if they: (i) conducted a twin study, (ii) investigated gender identity or gendered behaviour, and (iii) provided an estimate of the magnitude of genetic or environmental contribution. After screening 290 non-duplicate titles and abstracts, 16 articles were included in the final review. Most eligible studies provided evidence of both genetic and environmental contributions to gender identity and gendered behaviour. For gendered behaviour, genetic contributions ranged from 0.10 to 0.77, non-shared environmental contributions ranged from 0.15 to 0.75, and shared environmental contributions ranged from 0.00 to 0.49. For gender identity, genetic contributions ranged from 0.00 to 0.84, non-shared environmental contributions ranged from 0.15 to 0.96 and shared environmental contributions ranged from 0.00 to 0.70. Given the variability in results and methodology between studies, the true magnitude of these contributions remains unclear. No consistent differences in contributions were identified between assigned males and assigned females. While there is also recent evidence that prenatal hormone exposure may contribute to gender identity, the overall evidence from the literature is inconsistent. Twin studies indicate both genetic and environmental contributions to gender diversity. These results are important to inform ongoing public debate in this area and highlight the complex interplay of both genetics and environment.

The impact of the COVID-19 pandemic on the wellbeing of 26,555 Dutch children and adolescents (ages 8-18, 50% female, 89% with parents born in the Netherlands) was investigated using three cohorts: a general population twin sample (NTR), a general population sample (KLIK), and a clinical sample (DREAMS). Data were collected in seven waves between 2020 and 2023. Linear mixed models were employed to examine changes in wellbeing, twin models were used to estimate genetic and environmental contributions, and a psychometric model was employed to explore potential rater bias. A 6.5% drop in wellbeing was observed at the onset of the pandemic in the NTR sample, followed by partial recovery but not a return to pre-pandemic levels. Mean wellbeing scores were consistently lower in the clinical cohort (DREAMS), which also showed different effects of age, gender, and parental educational attainment compared to the two general population samples (NTR and KLIK). Increased disagreement between fathers' and mothers' ratings during lockdown was also identified. Genetic factors were found to account for 26-28% of the variance in wellbeing during the pandemic, and 34-35% before and after. Shared environmental factors were higher during the lockdown period (60-62%) compared to before and after the lockdown (45-49%), indicating the key role of family and home environment in that period. Multi-rater analyses suggested that part of this increase in shared environmental variance likely reflects rater bias rather than true environmental influences. These findings highlight that children in psychiatric care may face additional challenges compared to their peers and emphasize the importance of multi-rater assessments. Results suggest that both genetic predispositions and environmental disruptions should be considered when developing strategies to support child wellbeing during crises.

Previous studies robustly link childhood peer victimization experience to the timing of substance use initiation. However, no study has investigated the contributions of genetic and environmental factors to this link. The current study focused on a sample of 779 twin pairs followed from age 9-10 to 19-20, which is racially/ethnically and socioeconomically representative of the greater Los Angeles area. The aims were to investigate (1) the associations between childhood victimization, including physical (e.g., kicking, pushing), verbal (e.g., taunting), and relational victimization (e.g., spreading rumors), and timing of substance use initiation, and (2) the contributions of genetic/environmental factors to these associations. Multinomial logistic regressions revealed several small associations, but none of these survived corrections for multiple testing. Univariate genetic models suggested genetic (A) and nonshared environmental influences (E) on verbal victimization (V_A = .43, V_E = .57), shared environmental (C) and nonshared environmental factors on relational victimization (V_C = .22, V_E = .78), and ambiguous familial influences and E on physical victimization (V_A = .34, V_E = .66; V_C = .26, V_E = .74). Timing of cigarette initiation were explained by A, C, and E (V_A = .48, V_C = .31, V_E = .21). Quantitative sex differences in contributions of A, C, and E were detected for alcohol (V_AM = .90, V_EM = .10; V_CF = .86, V_EF = .14) and marijuana initiation (V_AM = .89, V_EM = .11; V_CF = .79, V_EF = .21); however, A could be dropped for females and C could be dropped for males across both variables. Multivariate twin analyses were not feasible, due to the low cross-trait correlations. These findings call into question the robustness of links between self-reported victimization in childhood and prospectively measured timing of substance initiation across adolescence.

Hand preference first appears in early development, yet twin studies and GWAS show that only a minority of variance is explained by heritable genetic factors. Using UK Biobank data and multivariable logistic regression to test associations between potential causes of handedness and offspring hand preference, we then investigated the potential causal effect of maternal smoking during pregnancy on offspring handedness using a proxy gene-by-environment (GxE) Mendelian randomization design. We used rs16969968 in the CHRNA5 gene and a polygenic risk score of genome-wide significant smoking-heaviness variants to proxy smoking behaviour. We stratified based on reported maternal smoking during pregnancy because, regardless of genotype, any causal effect of maternal smoking heaviness on offspring handedness should only manifest in individuals whose mothers smoked during pregnancy. Using traditional epidemiological methods, we found maternal smoking during pregnancy increased the probability of being right-handed after adjustment for covariates. Despite this, when using the GxE MR analyses we found no strong causal effect of maternal smoking during pregnancy on offspring hand-preference. Our findings using the UK Biobank cohort align with previous findings and emphasise the impact of factors such as birth year, birthweight, being part of a multiple birth and breastfeeding on hand preference. However, we found no strong evidence for a causal link between maternal smoking and offspring handedness. The main factors contributing to variation in hand preference remain unresolved.

Mitochondrial DNA (mtDNA) plays a crucial role in numerous cellular processes, yet its impact on human complex behavior remains underexplored. The current paper proposes a novel covariance structure model with seven parameters to specifically isolate and quantify mtDNA effects on human complex traits. This approach uses extended pedigrees to obtain estimates of mtDNA variance while controlling for other genetic and environmental influences. Our Monte-Carlo simulations indicate that a sample size of approximately 5,000 individuals is sufficient to detect medium mtDNA effects ([Formula: see text]), while a more substantial cohort of around 30,000 is required for small effects ([Formula: see text]). We show that deeper pedigrees increase power to detect the mtDNA effect while wider pedigrees decrease power, given the equal total sample size. We evaluated how missing kinship records and mtDNA mutations impact bias. Both lead to underestimation of mtDNA variance, and an overestimation of the interaction between nuclear DNA and mtDNA. In addition, the false positive rate of mtDNA effect estimation is low when fitting the model with data generated without mtDNA effects. Collectively, we demonstrate that using extended pedigrees to quantify the influence of mtDNA on human behavior is robust and powerful.

Substance use has been associated with differences in adult brain morphology; however, it is unclear whether these differences precede or are a result of substance use substance use. We investigated the impact of polygenic risk scores (PRSs) for cannabis use disorder (CUD) and general substance use and substance use disorder liability (SU/SUD) on brain morphology in drug-naïve adolescents. Baseline data were used from 1874 European-descent participants (ages 9-11) comprising 222, 328 and 387 pairs of MZ twins, DZ twins, and Non-Twin Siblings, respectively, in the Adolescent Brain Cognitive Development Study. We fitted multivariate twin models to estimate the putative effects of CUD, SU/SUD, and brain region-specific PRSs. These models assessed their influence on six subcortical and two cortical phenotypes. PRS for CUD and SU/SUD were created based on GWAS conducted by Johnson et al. (Lancet Psychiatry 7:1032, 2020) and Hatoum et al. (Nat Ment Health 1:210-223, 2023), respectively. When decomposing variance in each brain region of interest (ROI), we used the corresponding ROI-specific PRS. Brain morphometry in drug-naive subjects was unrelated to CUD PRS. The variance explained in each ROI by its corresponding PRS ranged from 0.8 to 4.4%. The SU/SUD PRS showed marginally significant effects (0.2-0.4%) on cortical surface area and nucleus accumbens volume, but overall effect sizes were small. This study failed to reject the null hypothesis of no association between genetic risk for substance use and brain morphometry among baseline drug-naive adolescents. Genetic risk for CUD was not associated with brain morphometry among drug-naive adolescents, but a weak association with general addiction and substance use risk (SU/SUD) particularly in nucleus accumbens volume and total cortical surface area, was observed.