Offspring Of Parents Research Articles

Anxiety and Disruptive Behavior Symptoms and Disorders in Preschool-Age Offspring of Parents With and Without Bipolar Disorder: Associations With Parental Comorbidity

Objective: We examined the relative contribution of parental bipolar disorder (BPD) and psychiatric comorbidities (disruptive behavior disorders [DBD] and anxiety disorders) in predicting psychiatric symptoms and disorders in 2-5-year-old offspring. Methods: Participants were 60 families with a parent with BPD and 78 offspring and 70 comparison families in which neither parent had a mood disorder and 91 offspring. Parent and offspring diagnoses and symptoms were assessed using standardized diagnostic interviews and measures, with offspring assessors masked to parental diagnoses. Results: Offspring of parents with BPD had significant elevations in behavioral, mood and anxiety disorders and symptoms. Both parental BPD and DBD contributed to elevations in child disruptive behavioral symptoms, whereas child anxiety symptoms were more strongly predicted by comorbid parental anxiety. Parental BPD was a stronger predictor than comorbid DBD of child DBDs. Conclusion: Some of the elevated risk for disorders in preschoolers is accounted for by parental comorbidity.

Lifestyle changes in Botryosphaeriaceae as evidenced by ancestral genome expansion and horizontal gene transfer

AbstractBotryosphaeriaceae (Botryosphaeriales, Dothideomycetes, Ascomycota) encompasses commonly encountered opportunistic pathogens that cause stem cankers on woody plants. Lifestyles of Botryosphaeriaceae species could vary as endophytes, pathogens and saprobes and one species can have one or more lifestyles. Therefore, this family is an excellent candidate to study the relationships among lifestyles and lifestyle changes. It is postulated that this family has saprobic ancestors, and the mechanisms by which they evolved from nonpathogenic ancestors to woody pathogens remain unclear. Here, we present an analysis of 18 Botryosphaeriaceae genomes, including four newly generated high-quality genomes of Botryosphaeriaceae strains. We compared Botryosphaeriaceae genomes with phylogenetically closely related Dothideomycetes taxa including plant pathogens and saprobes which revealed significant net gene family expansion in Botryosphaeriaceae. This gene expansion is prominent in the early ancestors before the divergence of genera of Botryosphaeriaceae. This expansion affected the pathogenicity-related genes and detoxification genes. Furthermore, we analysed horizontal gene transfer, which is a mechanism of transfer to genetic material between organisms that are not in a parent–offspring relationship and identified widespread putative intra-kingdom horizontal gene transfer events in this family. Most were transferred during the evolution of ancient ancestors of Botryosphaeriaceae, before the divergence of the modern genera and were enriched in pathogenicity-related genes and detoxification genes. Furthermore, The RNA sequencing analysis of the Botryosphaeriaceae species Lasiodiplodia theobromae revealed that pathogenicity-related genes and detoxification genes, including those obtained through gene family expansion and horizontal gene transfers, were significantly induced after the infection of plant hosts rather than before infection. These insights reveal critical roles for gene family expansion and horizontal gene transfers in the evolutionary adaptation of Botryosphaeriaceae in the infection of woody plants. We postulate that the pathogenic lifestyle of Botryosphaeriaceae species evolved from saprobic or endophytic lifestyles in the early divergence of this family. However, there are few endophytic genomes available for closely related species of Botryosphaeriaceae, thus further studies are necessary to clarify the evolutionary relationships of the endophytes.

Clinical and sociodemographic features in offspring aged 0-3 years of mothers with schizophrenia spectrum disorders. A descriptive cross-sectional study.

Offspring of parents with schizophrenia spectrum disorders (SSD) have an increased risk of neurodevelopmental disturbances. However, the ability to provide very early interventions to support these children and their families requires profound knowledge regarding characteristic features of both the parents and their offspring. Information on this subject is currently sparse. The aim of the present study is to investigate clinical and sociodemographic variables in offspring in the age range of 0-3 years of mothers diagnosed with SSD. The study is descriptive with a cross-sectional design and includes parent-child dyads consisting of mothers diagnosed with SSD (ICD-10: F20-29) and their offspring aged 0-3 years, who were referred for examination and intervention at the infant and toddler psychiatric units, at the Mental Health Services, Capital Region, Copenhagen University Hospitals in two locations (Bispebjerg and Glostrup). Clinical and sociodemographic data were extracted from the Copenhagen "Infant Psychiatric Database" and processed by descriptive analysis. Out of 95 parent-child dyads considered for the study population, 85 were included. 27.8% of the mothers had psychiatric comorbidities, and 18.9% of the fathers had a psychiatric diagnosis at the time of investigation. Of the children, 89.7% were born full term (≥37th week) and most of them had a birth weight of ≥2500 g (81.8%). Of the mothers, 50% had experienced pregnancy complications of varying severity. Birth complications were seen in 62.9% of the dyads. Psychopathology was identified in 50% of the children at age 0-3 years, and 62.2% of the parent-child dyads appeared to have an affected relationship. Results show widespread psychopathology in offspring aged 0-3 years of mothers with SSD. Moreover, several psychosocial stressors, clinical parental features, and relational disturbances are identified. These results contribute to a better understanding and identification of early risk markers of long-term psychopathology in this infant patient group, and hence serve as potential targets for early interventions.

Parental cardiovascular disease and cardiovascular disease risk factors in the offspring: The Diet, Cancer and Health cohorts

Background and aimsCardiovascular disease (CVD) aggregates in families and offspring with parental CVD may have adverse risk factor levels long time before the potential onset of CVD. We compared risk factor levels in offspring of parents with atherosclerotic CVD (ASCVD) and parents with no ASCVD at different parental ages at onset. MethodsThe study included 5751 participants (median age: 50 years) of the Diet, Cancer and Health - Next Generations study. Measurements included blood pressure, body composition and lipid fractions. Information on parental ASCVD and age at disease onset was obtained through register linkage. Parental ASCVD was defined as myocardial infarction, ischemic stroke or peripheral artery disease occurring <70 years, prematurely (mothers: <65 years fathers: <55 years), divided into age categories or using a broader classification of CVD. Linear regression models using Generalized Estimating Equations were used for analysis. Analyses were adjusted for age, sex, education, smoking, alcohol intake, physical activity and some additionally for BMI. ResultsOffspring with parental ASCVD had a higher blood pressure, waist circumference, BMI, visceral adipose tissue, percentage of body fat and non-HDL cholesterol levels, but not other lipid levels, compared to offspring with no parental ASCVD (all p < 0.01). Overall, the same patterns were observed for parental ASCVD occurring prematurely and using a broader CVD classification. ConclusionsOffspring with parental ASCVD had a higher blood pressure, higher body composition measures and higher non-HDL cholesterol levels compared to offspring with no parental ASCVD. Findings were overall consistent across different classifications of parental ASCVD.

Structural Brain Correlates of Physical Activity in Offspring of Parents with and without Exceptional Longevity

AbstractBackgroundPrevious studies suggest that frequent participation in physical activities (PA) promotes healthy aging by decreasing late‐life morbidity. Several studies further suggest that the volume of the prefrontal cortex and the hippocampus increases in response to PA. Brain volume is also preserved among offspring of those with exceptional longevity. This research examined associations between self‐reported PA and gray matter volume in older adults without dementia, and as function of parental longevity.MethodsSelf‐reported PA (activity level (low/high); activity rating (low/high); city blocks walked (&lt;10/≥10); weekly aerobic exercise (&lt;4/≥4); flights of stairs (≤5/&gt;5); longest continuous walk (&lt;4/≥4) and structural MRI data from 107 Ashkenazi Jewish older adults (79.08±6.52 years; 57.94% women) was examined. 59.81% of participants were offspring of parents with exceptional longevity (at least one parent lived 95 years or more) and 40.19% were offspring of parents with usual survival (both parents lived less than 95 years). Voxel‐based morphometry and multivariate covariance‐based analyses – adjusted for age, sex, years of education, and total intracranial volume – were used to identify gray matter patterns associated with PA. Linear regression was used to determine if these patterns varied as a function of parental longevity.ResultsSignificant gray matter covariance patterns associated with PA ratings (p = 0.001) and flight of stairs (p = 0.004) were derived. The gray matter pattern associated with flight of stairs were primarily composed of middle cingulate, thalamus, superior frontal gyrus and insula. The gray matter pattern associated with PA level were primarily composed of caudate nucleus, insula, and hippocampus. None of the derived gray matter patterns varied as a function of parental longevity. No significant patterns were observed for city blocks walked, weekly exercise, or longest continuous walk.ConclusionOur results suggest that self‐reported PA – when assessed with activity rating and flight of stairs climbed – are associated with gray matter volume pattern composed of hippocampal, cingulate, insular, and prefrontal regions. Our results further demonstrated that these gray matter patterns do not vary as a function of parental longevity. Participating in PA may benefit the aging brain to a similar extent in offspring of parents with and without exceptional longevity.

Association Between Parental BMI and Offspring's Blood Pressure by Mediation Analysis: A Study Using Data From the Korean National Health and Nutrition Examination Survey.

This study analyzed the relationship between parental body mass index (BMI; BMI_p) and hypertension in their adolescent offspring (HTN_a), focusing on the mediating effect of adolescents' BMI (BMI_a). Utilizing data from the Korea National Health and Nutrition Examination Survey, including participants aged 12-18, we conducted a mediation analysis while controlling for confounding factors such as age, sex, physical activity, dietary habits, household income quartile, and parents' alcohol and smoking habits. The study included a total of 5731 participants, of whom 3381 and 5455 participants had data on fathers' and mothers' BMI, respectively. For adolescent systolic blood pressure (SBP_a), the father's BMI (BMI_f) had a significant total effect (β, 0.23; 95% confidence interval [CI], 0.12 to 0.34) and average controlled mediated effect (ACME) (β, 0.27; 95% CI, 0.23 to 0.32), but the average direct effect (ADE) was not significant. The mother's BMI (BMI_m) had a significant total effect (β, 0.17; 95% CI, 0.09 to 0.25), ACME (β, 0.25; 95% CI, 0.22 to 0.28) and ADE (β, -0.08; 95% CI, -0.16 to 0.00). For adolescent diastolic blood pressure, both BMI_f and BMI_m had significant ACMEs (β, 0.10; 95% CI, 0.08 to 0.12 and β, 0.09; 95% CI, 0.07 to 0.12, respectively), BMI_m had a significant ADE (β, -0.09; 95% CI, -0.16 to -0.02) but BMI_f had an insignificant ADE and total effect. The study found that parental BMI had a significant effect on SBP_a, mediated through BMI_a. Therefore, a high BMI in parents could be a risk factor, mediated through BMI_a, for systolic hypertension in adolescents, necessitating appropriate management.

Differential diagnosis of chorea (guidelines of the German Neurological Society)

IntroductionChoreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements. They typically increase in intensity with stress and physical activity and essentially cease during deep sleep stages. In particularly in advanced stages of Huntington disease (HD), choreiform hyperkinesia occurs alongside with dystonic postures of the limbs or trunk before they typically decrease in intensity.Summary or definition of the topicThe differential diagnosis of HD can be complex. Here, the authors aim to provide guidance for the diagnostic process. This guidance was prepared for the German Neurological Society (DGN) for German-speaking countries.RecommendationsHereditary (inherited) and non-hereditary (non-inherited) forms of chorea can be distinguished. Therefore, the family history is crucial. However, even in conditions with autosomal-dominant transmission such as HD, unremarkable family histories do not necessarily rule out a hereditary form (e.g., in cases of early deceased or unknown parents, uncertainties in familial relationships, as well as in offspring of parents with CAG repeats in the expandable range (27–35 CAG repeats) which may display expansions into the pathogenic range).ConclusionsThe differential diagnosis of chorea can be challenging. This guidance prepared for the German Neurological Society (DGN) reflects the state of the art as of 2023.

Risk factors for mood disorders among offspring of parents with bipolar disorder: Findings from a discordant-sibling study

The purpose of this naturalistic, prospective study was to identify risk factors for mood disorders in offspring of parents with bipolar disorder (BPD) using the discordant-sibling design by comparing premorbid psychopathology or symptoms, temperament, personality traits and coping style as well as the perception of family-related characteristics among affected and unaffected siblings within the same family. This approach controls for confounding by unmeasured genetic and environmental factors shared within families. Our sample comprised 24 families of a parent with BPD with at least one child that developed BPD or major depressive disorder (n=31), and at least one child who did not. Offspring were followed for a mean duration of 16.2 (s.d: 4.6) years. Information was collected from the offspring themselves. Generalized linear mixed models only revealed differences in three dimensions of the Dimension of Temperament Survey-Revised (DOTS-R) version: Offspring with mood disorders scored higher on "Approach-withdrawal", "Rhythmicity for daily habits", and "Task orientation" than their unaffected siblings. The higher scores, and not lower scores as expected, on these temperament dimensions observed in offspring that subsequently developed mood disorders may reflect increased vulnerability, but they could also mirror premorbid mood swings or strategies to cope with them.

Parental fructose consumption induces early baroreflex dysfunction in offspring: impact on arterial pressure and on insulin resistance.

Fructose overconsumption is a worldwide trend, and it has been found to cause metabolic disorders in parents and their offspring. Additionally, metabolic syndrome has been closely associated with increased cardiovascular risk. In this study, we hypothesized that the chronic fructose consumption by parents could trigger autonomic dysfunction and cardiometabolic disorders in their offspring. Wistar rats undergo an intake of 10% of fructose in drinking water or regular water for 60 days before mating. Their offspring, control (C) and fructose (F) groups, were evaluated 30 days after weaning. Lower birth weight, increased levels of blood triglycerides and insulin resistance were observed in F compared to C group. The offspring of the fructose parents showed increased mean arterial pressure (C: 104 ± 1 vs. F: 111 ± 2 mmHg) and baroreflex sensitivity impairment, characterized by reduced bradycardic (C: -1.6 ± 0.06 vs. F: -1.3 ± 0.06 bpm/mmHg) and tachycardic responses (C: -4.0 ± 0.1 vs. F: -3.1 ± 0.2 bpm/mmHg). Finally, a higher baroreflex-induced tachycardia was associated with lower insulin tolerance (r = -0.55, P < 0.03) and higher systolic arterial pressure (r = 0.54, P < 0.02). In conclusion, our findings indicate that the excessive consumption of fructose by parents is associated with early autonomic, cardiovascular, and metabolic derangement in the offspring, favoring an increased cardiometabolic risk when they reach adulthood.

Distinct patterns of inheritance shape life-history traits in steelhead trout.

Life-history variation is the raw material of adaptation, and understanding its genetic and environmental underpinnings is key to designing effective conservation strategies. We used large-scale genetic pedigree reconstruction of anadromous steelhead trout (Oncorhynchus mykiss) from the Russian River, CA, USA, to elucidate sex-specific patterns of life-history traits and their heritability. SNP data from adults returning from sea over a 14-year period were used to identify 13,474 parent-offspring trios. These pedigrees were used to determine age structure, size distributions and family sizes for these fish, as well as to estimate the heritability of two key life-history traits, spawn date and age at maturity (first reproduction). Spawn date was highly heritable (h2 = 0.73) and had a cross-sex genetic correlation near unity. We provide the first estimate of heritability for age at maturity in ocean-going fish from this species and found it to be highly heritable (h2 from 0.29 to 0.62, depending on sex and method), with a much lower genetic correlation across sexes. We also evaluated genotypes at a migration-associated inversion polymorphism and found sex-specific correlations with age at maturity. The significant heritability of these two key reproductive traits in these imperiled fish, and their patterns of inheritance in the two sexes, is consistent with predictions of both natural and sexually antagonistic selection (sexes experience opposing selection pressures). This emphasizes the importance of anthropogenic factors, including hatchery practices and ecosystem modifications, in shaping the fitness of this species, thus providing important guidance for management and conservation efforts.

Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019).

The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults. This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability. The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69-3.10; P=0.027-0.038), especially in daughters (OR, 2.04-4.64; P=0.029-0.034). HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Abstract 13282: Parental Allostatic Load Predicts Time to the Onset of Cardiovascular Disease in Offspring

Background: Allostatic load, a measure of cumulative stress-related physiologic dysregulation, is associated with major cardiovascular disease (CVD) events. However, despite evidence of familial aggregation of CVD risk factors, the impact of parental allostatic load on the onset and timing of CVD in offspring remains unknown. Hypothesis: We hypothesize that offspring of parents with lower allostatic load will have longer CVD-free survival time. Aim: To examine whether CVD-free survival in offspring is associated with parental allostatic load and potential sex-specific differences. Methods: A secondary data analysis of 6,145 offspring-mother-father trios derived from the Framingham Heart Study Original (exam 10) and Offspring Cohorts (exam 1). Allostatic load was defined as an index (0-16) of 8 variables (systolic and diastolic blood pressure, total cholesterol, HDL, LDL, total cholesterol/ HDL ratio, fasting blood glucose and body mass index). Kaplan-Meier plots, and Irwin’s restricted mean and multivariable-adjusted Cox proportional hazards regression models were used to examine sex-specific differences and the association between parental allostatic load and offspring’s CVD-free survival. Results: Parents mean age (SD) was 60.8 (8.1) and offspring’s 34.8 (10.5). 22.8% of parents (n=458) and 12.1% (n=412) of offspring had high allostatic load (&gt;8). In a total of 118,132 person-years of follow-up among the offspring, 1060 incident CVD events occurred. The overall CVD incidence rate was 8.9 per 1000 person-years (95% confidence interval [CI] 8.4-9.5) and sons had a higher CVD incident rate than daughters (11.0 vs 7.2, p&lt;0.001). Offspring of mothers with low allostatic load lived 4 more years free of CVD compared to offspring of mothers with high allostatic load. Similarly, offspring of fathers with low allostatic load lived 3 more years free of CVD. The hazard rate of having incident CVD among offspring of mothers and fathers with high (compared to low) allostatic load was 1.58 (1.28-1.95) and 1.39 (95% CI: 1.11-1.75), respectively. Conclusion: Parents' allostatic load has a significant impact on the cardiovascular health of their offspring, with those of mothers with high allostatic load being at a higher risk of developing CVD at a younger age.

The Impact of Consanguineous Marriage on Children’s Human Capital in Pakistan

Cousin marriage is an important social institution in many parts of Asia and Africa; yet few studies have looked beyond the health consequences to its role in shaping intrahousehold dynamics. We use a unique survey of households in Pakistan to examine the role of parental consanguinity on education, child work and vaccination, and how those effects differ by gender. We apply ordinary least squares, Tobit, inverse probability weighting with regression adjustment treatment effects and intent-to-treat estimation techniques to a dataset of 1,020 households from 9 districts and control for a rich set of covariates. We model selection into consanguineous marriage using the availability of opposite-gender marriageable cousins. Our results show that the adult children of parents who are first cousins completed fewer years of education and are less likely to have attended school. Educational attainment was curtailed equally for daughters of both marriage arrangements, but consanguineous daughters faced a double burden of consanguinity and gender discrimination. For school-aged children of consanguineous couples, the number of days of school missed is higher in some specifications, but enrolment and educational expenditures are roughly the same as children of parents who are not related or are related more distantly. In contrast, domestic work is somewhat reduced for the offspring of first-cousin parents. Daughters of consanguineous parents are less likely to have received vaccinations, although this effect is weaker in the sample of school-aged children than adult children.

A Multigenerational Turing Model Reproduces Transgressive Petal Spot Phenotypes in Hybrid Mimulus

The origin of phenotypic novelty is a perennial question of genetics and evolution. To date, few studies of biological pattern formation specifically address multi-generational aspects of inheritance and phenotypic novelty. For quantitative traits influenced by many segregating alleles, offspring phenotypes are often intermediate to parental values. In other cases, offspring phenotypes can be transgressive to parental values. For example, in the model organism Mimulus (monkeyflower), the offspring of parents with solid-colored petals exhibit novel spotted petal phenotypes. These patterns are controlled by an activator-inhibitor gene regulatory network with a small number of loci. Here we develop and analyze a model of hybridization and pattern formation that accounts for the inheritance of a diploid gene regulatory network composed of either homozygous or heterozygous alleles. We find that the resulting model of multi-generational Turing-type pattern formation can reproduce transgressive petal phenotypes similar to those observed in Mimulus. The model gives insight into how non-patterned parent phenotypes can yield phenotypically transgressive, patterned offspring, aiding in the development of empirically testable hypotheses.

Relations among symptoms of depression over time in at-risk youth.

Depression consists of symptoms that may relate to each other in ways that go beyond simple co-occurrence. For example, some symptoms may precede and possibly contribute to the emergence of others. The present study examined several potential relations among the symptoms of depression. The overarching goals were to better understand how depression may unfold and to identify potential targets for intervention. The sample included 120 offspring of depressed parents. Youths' symptoms of depression were rated across 89 weeks. First, we investigated which symptoms preceded and potentially contributed to other symptoms 1 week later. This model revealed that sleep disturbance predicted the occurrence of other symptoms (e.g., sad mood, fatigue), and the occurrence of sad mood was predicted by other symptoms (e.g., worthlessness/guilt, psychomotor symptoms, sleep disturbance). Second, we investigated the within-person question of which symptoms tended to co-occur at the same time point. This model identified sad mood, irritability, and anhedonia as symptoms that tended to co-occur with each other and with many other depressive symptoms. Third, we investigated the between-person question of which symptoms tended to co-occur when averaged across time. This model identified worthlessness/guilt, fatigue, and anhedonia as symptoms strongly associated with other depressive symptoms across people irrespective of timing. Results indicate that the relations among the symptoms of depression vary, such that some symptoms preceded others by 1 week, some symptoms occurred at the same time, and other symptoms co-occurred in individuals. This more detailed view of the connections among depressive symptoms informs our understanding of depression as a dynamic set of unique indicators. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Associations between parental adherence to healthy lifestyles and cognitive performance in offspring: A prospective cohort study in China.

Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring's cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring's cognitive performance during adolescence and young adulthood in China. We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring's fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018). Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring's healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring's cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring's overall crystallized intelligence. Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring's cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Purifying and balancing selection on embryonic semi-lethal haplotypes in a wild mammal.

Embryonic lethal mutations are arguably the earliest and most severe manifestation of inbreeding depression, but their impact on wild populations is not well understood. Here, we combined genomic, fitness, and life-history data from 5,925 wild Soay sheep sampled over nearly three decades to explore the impact of embryonic lethal mutations and their evolutionary dynamics. We searched for haplotypes that in their homozygous state are unusually rare in the offspring of known carrier parents and found three putatively semi-lethal haplotypes with 27%-46% fewer homozygous offspring than expected. Two of these haplotypes are decreasing in frequency, and gene-dropping simulations through the pedigree suggest that this is partially due to purifying selection. In contrast, the frequency of the third semi-lethal haplotype remains relatively stable over time. We show that the haplotype could be maintained by balancing selection because it is also associated with increased postnatal survival and body weight and because its cumulative frequency change is lower than in most drift-only simulations. Our study highlights embryonic mutations as a largely neglected contributor to inbreeding depression and provides a rare example of how harmful genetic variation can be maintained through balancing selection in a wild mammal population.

Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders

Mood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts. To examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls. This community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools. The youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder. Body mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight. Of 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (β = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (β = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age. In this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.

Genomic Prediction of Tree Height, Wood Stiffness, and Male Flower Quantity Traits across Two Generations in Selected Individuals of Cryptomeria japonica D. Don (Japanese Cedar)

Breeding long-lived trees is challenging, but it has been shown that genomic information can be used to improve efficiency. In this study, genomic prediction (GP) was tested on selected individuals of a two-generation breeding population of Cryptomeria japonica, the most common plantation tree in Japan. In the 1980s, the second-generation plus trees (101 clones) were selected from about 8500 individuals obtained by cross-mating the first-generation plus trees (47 clones). RAD-seq based on 8664 SNPs was used to perform GP for three important traits in this population: tree height, wood stiffness, and male flower quantity. The association between traits and genotypes was modeled using five Bayesian models whose predictive accuracy was evaluated by cross-validation, revealing that the best model differed for each trait (BRR for tree height, BayesA for wood stiffness, and BayesB for male flower quantity). GP was 1.2–16.0 times more accurate than traditional pedigree-based methods, attributed to its ability to model Mendelian sampling. However, an analysis of the effects of intergenerational kinship showed that parent–offspring relationships reduce the predictive accuracy of GP for traits strongly affected by selection pressure. Overall, these results show that GP could significantly expedite tree breeding when supported by a deep understanding of the targeted population’s genetic background.

Parental Exposure to Environmentally Relevant Concentrations of Bisphenol-A Bis(diphenyl phosphate) Impairs Vascular Development in Offspring through DNA/RNA Methylation-Dependent Transmission.

Bisphenol-A bis(diphenyl phosphate) (BDP) has been increasingly detected in indoor environmental and human samples. Little is known about its developmental toxicity, particularly the intergenerational effects of parental exposure. In this study, adult zebrafish were exposed to BDP at 30-30,000 ng/L for 28 days, with results showing that exposure did not cause a transfer of BDP or its metabolites to offspring. Vascular morphometric profiling revealed that parental exposure to BDP at 30 and 300 ng/L exerted significant effects on the vascular development of offspring, encompassing diverse alterations in multiple types of blood vessels. N6-Methyladenosine (m6A) methylated RNA immunoprecipitation sequencing of larvae in the 300 ng/L group revealed 378 hypomethylated and 350 hypermethylated m6A peaks that were identified in mRNA transcripts of genes crucial for vascular development, including the Notch/Vegf signaling pathway. Concomitant changes in 5 methylcytosine (m5C) DNA methylation and gene expression of m6A modulators (alkbh5, kiaa1429, and ythdf1) were observed in both parental gonads and offspring exposed to BDP. These results reveal that parental exposure to low concentrations of BDP caused offspring vascular disorders by interfering with DNA and RNA methylation, uncovering a unique DNA-RNA modification pattern in the intergenerational transmission of BDP's developmental toxicity.