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BackgroundChaotic home environments may contribute to children's attention-deficit hyperactivity disorder (ADHD) symptoms. However, ADHD genetic risk may also influence household chaos. This study investigated whether children in chaotic households had more ADHD symptoms, if mothers and children with higher ADHD genetic risk lived in more chaotic households, and the joint association of genetic risk and household chaos on the longitudinal course of ADHD symptoms across childhood.MethodsParticipants were mothers and children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative birth cohort of 2,232 twins. Children's ADHD symptoms were assessed at ages 5, 7, 10 and 12 years. Household chaos was rated by research workers at ages 7, 10 and 12, and by mother's and twin's self-report at age 12. Genome-wide ADHD polygenic risk scores (PRS) were calculated for mothers (n = 880) and twins (n = 1,999); of these, n = 871 mothers and n = 1,925 children had information on children's ADHD and household chaos.ResultsChildren in more chaotic households had higher ADHD symptoms. Mothers and children with higher ADHD PRS lived in more chaotic households. Children's ADHD PRS was associated with household chaos over and above mother's PRS, suggesting evocative gene–environment correlation. Children in more chaotic households had higher baseline ADHD symptoms and a slower rate of decline in symptoms. However, sensitivity analyses estimated that gene–environment correlation accounted for a large proportion of the association of household chaos on ADHD symptoms.ConclusionsChildren's ADHD genetic risk was independently associated with higher levels of household chaos, emphasising the active role of children in shaping their home environment. Our findings suggest that household chaos partly reflects children's genetic risk for ADHD, calling into question whether household chaos directly influences children's core ADHD symptoms. Our findings highlight the importance of considering parent and child genetic risk in relation to apparent environmental exposures.

Supplemental Material for An Early and Unequal Decline: Life Course Trajectories of Cognitive Aging in the Unites States by Yang C. Yang, Christine E. Walsh, Kaitlin Shartle, Rebecca C. Stebbins, Allison E. Aiello, Daniel W. Belsky, Kathleen Mullan Harris, Marianne Chanti-Ketterl, and Brenda L. Plassman in Journal of Aging and Health

Aging is a process of progressive change. To develop biological models of aging, longitudinal datasets with high temporal resolution are needed. Here we report a multi-omics longitudinal dataset for cultured primary human fibroblasts measured across their replicative lifespans. Fibroblasts were sourced from both healthy donors (n = 6) and individuals with lifespan-shortening mitochondrial disease (n = 3). The dataset includes cytological, bioenergetic, DNA methylation, gene expression, secreted proteins, mitochondrial DNA copy number and mutations, cell-free DNA, telomere length, and whole-genome sequencing data. This dataset enables the bridging of mechanistic processes of aging as outlined by the “hallmarks of aging”, with the descriptive characterization of aging such as epigenetic age clocks. Here we focus on bridging the gap for the hallmark mitochondrial metabolism. Our dataset includes measurement of healthy cells, and cells subjected to over a dozen experimental manipulations targeting oxidative phosphorylation (OxPhos), glycolysis, and glucocorticoid signaling, among others. These experiments provide opportunities to test how cellular energetics affect the biology of cellular aging. All data are publicly available at our webtool: https://columbia-picard.shinyapps.io/shinyapp-Lifespan_Study/

Additional file 1: Supplementary Table 1. Regression table describing the association between standardized, natural-log 4-week antibody titres and ΔBA in high-dose recipients, including a two-way interaction between ΔBA and CMV serostatus. Supplementary Table 2. KDM training parameters derived from the CLSA and used calculate biological aging in the vaccination cohort. Supplementary Figure 1. Characteristics of KDM biological age (BA) in the CLSA training cohort and associations with the frailty index (FI). A) Pearson’s correlation (R) for BA with chronological age and significance (p) for females (red asterisk) and males (blue dots). B) Distribution of ΔBA in females and males, including the mean and standard deviation. C) Differences in years for ΔBA (and 95% confidence interval) for pre-frail (0.10=FI

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

Objectives To test whether frequent bullying victimisation in childhood increases the likelihood of self harming in early adolescence, and to identify which bullied children are at highest risk of self harm.Design The Environmental Risk (E-Risk) longitudinal study of a nationally representative UK cohort of 1116 twin pairs born in 1994-95 (2232 children).Setting England and Wales, United Kingdom.Participants Children assessed at 5, 7, 10, and 12 years of age.Main outcome measures Relative risks of children���s self harming behaviour in the six months before their 12th birthday. Results Self harm data were available for 2141 children. Among children aged 12 who had self harmed (2.9%; n=62), more than half were victims of frequent bullying (56%; n=35). Exposure to frequent bullying predicted higher rates of self harm even after children���s pre-morbid emotional and behavioural problems, low IQ, and family environmental risks were taken into account (bullying victimisation reported by mother: adjusted relative risk 1.92, 95% confidence interval 1.18 to 3.12; bullying victimisation reported by child: 2.44, 1.36 to 4.40). Victimised twins were more likely to self harm than were their non-victimised twin sibling (bullying victimisation reported by mother: 13/162 v 3/162, ratio=4.3, 95% confidence interval 1.3 to 14.0; bullying victimisation reported by child: 12/144 v 7/144, ratio=1.7, 0.71 to 4.1). Compared with bullied children who did not self harm, bullied children who self harmed were distinguished by a family history of attempted/completed suicide, concurrent mental health problems, and a history of physical maltreatment by an adult.Conclusions Prevention of non-suicidal self injury in young adolescents should focus on helping bullied children to cope more appropriately with their distress. Programmes should target children who have additional mental health problems, have a family history of attempted/completed suicide, or have been maltreated by an adult.

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used Genomic Structural Equation Modeling and prior genome-wide association studies (GWAS) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability.We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Non-cognitive genetics were enriched in the same brain tissues and cell types as cognitive performance but showed different associations with gray-matter brain volumes. Non-cognitive genetics were further distinguished by associations with personality traits, less risky behavior,and increased risk for certain psychiatric disorders.For socioeconomic success and longevity, non-cognitive and cognitive-performance genetics demonstrated similar-magnitude associations. By conducting a GWAS of a phenotype that was not directly measured, we offer a first view of genetic architecture of non-cognitive skills influencing educational success.

Adverse childhood experiences (ACEs) can affect development in ways that disrupt the formation of human capital and contribute to later-life morbidity and mortality. Theories of development predict that the timing of adversity will affect its outcomes. However, empirical evidence for timing-specific effects remains scant. In this issue of JAMA Network Open, Andersen 1 reports an analysis of population-register data from Denmark that suggests timing-specific associations of household dysfunction ACEs with young people's successful transition to adulthood. Andersen's study 1 linked data from several Danish registers to compose records tracking children born between 1987 and 1995 and their families from the child's birth until they reached age 19 years. The analysis tested how exposure to household dysfunction ACEs during ages 0 to 2, 3 to 5, 6 to 12, and 13 to 17 years were associated with disruptions in children's transition to adulthood. Children's ACE exposure was measured from records of parental unemployment, incarceration, psychiatric diagnoses, and divorce as well as children's placement in foster care. Disruption to the transition to adulthood was measured from records of education, employment, criminal charges, and psychiatric diagnoses. Andersen's analysis 1 compared siblings in the same family who experienced household dysfunction ACEs at different stages of development, eg, when a younger sibling's early-childhood exposure was simultaneously their older sibling's middle-childhood exposure. Using this sibling comparison design, Andersen identified a dose-response association between accumulation of ACEs and increased likelihood of experiencing disruption to the transition to adulthood. Adversity exposures during adolescence (ages 13-17 years) had larger magnitude risk associations compared with adversities that occurred earlier in development. Effect sizes for adolescent exposures were nearly 2-fold those for exposures in middle childhood and more than 3-fold those for exposures earlier in life. The findings of stronger associations for exposures during adolescence contrast with the popular narrative of the first 1000 days as a unique window of opportunity to promote positive development. 2 They are also at odds with theoretical estimates from models of dynamic skill formation, which suggest that investments during early childhood should have higher returns than investments later in life. 3 Andersen's results 1 resonate with emerging research streams in both neuroscience and the social sciences to suggest that benefits of interventions in adolescence may be underappreciated. The US Centers for Disease Control and Prevention ACE Pyramid 4 proposes that childhood adversity affects future health through pathways of disrupted neurodevelopment, leading to social and cognitive impairment and the adoption of health risk behaviors. One reason for an early-childhood focus in intervention efforts is the concentration of critical periods in neurodevelopment in the first years of life. 5 However, as Andersen notes, 1 this same logic may also encourage focus on adolescence. New science suggests that adolescence is a second critical period in neurodevelopment, characterized by experience-dependent plasticity affecting higher-order cognitive functions, including memory and self-control. 6 Robust development of these higher-order cognitive functions is essential for a successful transition to adulthood and for health and well-being across adult life. If household dysfunction during adolescence interferes with this development, consequences for the transition to adulthood and beyond may be substantial. Setting aside specific neurodevelopmental vulnerability, adolescence may also be thought of as a critical period in children's human capital development. During adolescence, heightened social sensitivity and increased sensation seeking 7 coincide with tracking into differentiated academic curricula and the first option to drop out of school. Even small disruptions in academic performance can severely reduce access to postsecondary education and future economic opportunities. One