Disentangling mechanisms behind the pleiotropic effects of proximal 16p11.2 BP4-5 CNVs.

Whereas 16p11.2 BP4-5 copy-number variants (CNVs) represent one of the most pleiotropic etiologies of genomic syndromes in both clinical and population cohorts, the mechanisms leading to such pleiotropy remain understudied. Identifying 73 deletion and 89 duplication carrier individuals among unrelated White British UK Biobank participants, we performed a phenome-wide association study (PheWAS) between the region's copy number and 117 complex traits and diseases, mimicking four dosage models. Forty-six phenotypes (39%) were affected by 16p11.2 BP4-5 CNVs, with the deletion-only, mirror, U-shape, and duplication-only models being the best fit for 30, 10, 4, and 2 phenotypes, respectively, aligning with the stronger deleteriousness of the deletion. Upon individually adjusting CNV effects for either body mass index (BMI), height, or educational attainment (EA), we found that sixteen testable deletion-driven associations-primarily with cardiovascular and metabolic traits-were BMI dependent, with EA playing a more subtle role and no association depending on height. Bidirectional Mendelian randomization supported that 13 out of these 16 associations were secondary consequences of the CNV's impact on BMI. For the 23 traits that remained significantly associated upon individual adjustment for mediators, matched-control analyses found that 10 phenotypes, including musculoskeletal traits, liver enzymes, fluid intelligence, platelet count, and pneumonia and acute kidney injury risk, remained associated under strict Bonferroni correction, with 10 additional nominally significant associations. These results paint a complex picture of 16p11.2 BP4-5's pleiotropic pattern that involves direct effects on multiple physiological systems and indirect co-morbidities consequential to the CNV's impact on BMI and EA, acting through trait-specific dosage mechanisms.

Using parent-offspring pairs and trios to estimate indirect genetic effects in education.

We investigated indirect genetic effects (IGEs), also known as genetic nurture, in education with a novel approach that uses phased data to include parent-offspring pairs in the transmitted/nontransmitted study design. This method increases the power to detect IGEs, enhances the generalizability of the findings, and allows for the study of effects by parent-of-origin. We validated and applied this method in a family-based subsample of adolescents and adults from the Lifelines Cohort Study in the Netherlands (N = 6147), using the latest genome-wide association study data on educational attainment to construct polygenic scores (PGS). Our results indicated that IGEs play a role in education outcomes in the Netherlands: we found significant associations of the nontransmitted PGS with secondary school level in youth between 13 and 24 years old as well as with education attainment and years of education in adults over 25 years old (ß = 0.14, 0.17 and 0.26, respectively), with tentative evidence for larger maternal IGEs. In conclusion, we replicated previous findings and showed that including parent-offspring pairs in addition to trios in the transmitted/nontransmitted design can benefit future studies of parental IGEs in a wide range of outcomes.

Robust genetic nurture effects on education: A systematic review and meta-analysis based on 38,654 families across 8 cohorts.

Similarities between parents and offspring arise from nature and nurture. Beyond this simple dichotomy, recent genomic studies have uncovered "genetic nurture" effects, whereby parental genotypes influence offspring outcomes via environmental pathways rather than genetic transmission. Such genetic nurture effects also need to be accounted for to accurately estimate "direct" genetic effects (i.e., genetic effects on a trait originating in the offspring). Empirical studies have indicated that genetic nurture effects are particularly relevant to the intergenerational transmission of risk for child educational outcomes, which are, in turn, associated with major psychological and health milestones throughout the life course. These findings have yet to be systematically appraised across contexts. We conducted a systematic review and meta-analysis to quantify genetic nurture effects on educational outcomes. A total of 12 studies comprising 38,654 distinct parent(s)-offspring pairs or trios from 8 cohorts reported 22 estimates of genetic nurture effects. Genetic nurture effects on offspring's educational outcomes (ßgenetic nurture = 0.08, 95% CI [0.07, 0.09]) were smaller than direct genetic effects (ßdirect genetic = 0.17, 95% CI [0.13, 0.20]). Findings were largely consistent across studies. Genetic nurture effects originating from mothers and fathers were of similar magnitude, highlighting the need for a greater inclusion of fathers in educational research. Genetic nurture effects were largely explained by observed parental education and socioeconomic status, pointing to their role in environmental pathways shaping child educational outcomes. Findings provide consistent evidence that environmentally mediated parental genetic influences contribute to the intergenerational transmission of educational outcomes, in addition to effects due to genetic transmission.

Preschool Mathematics and Literacy Skills and Educational Attainment in Adolescents Born Preterm and Full Term.

OBJECTIVES: To test whether preschool academic skills were associated with educational attainment in adolescence and whether associations differed between individuals born preterm and at full term. STUDY DESIGN: This prospective cohort study comprised 6924 individuals, including n = 444 (6.4%) adolescents born preterm (<37 weeks of gestation) from the Avon Longitudinal Study of Parents and Children. Preschool academic (mathematics and literacy) skills were rated by teachers at 4-5 years. Educational attainment at 16 years was informed by attaining a General Certificate of Secondary Education (GCSE) in key subjects mathematics and English. Logistic regressions assessed the association between preterm birth, preschool mathematics, and GCSE Mathematics and between preterm birth, preschool literacy, and GCSE English. RESULTS: Similar numbers of adolescents born preterm and at term achieved a GCSE in mathematics and English (53.6 % vs 57.4% and 59.5% vs 63.9%, respectively; P values > .05). Higher preschool academic skill scores in mathematics were associated with greater odds of attaining GCSE Mathematics and preschool literacy skills were associated with GCSE English. Adolescents born preterm with higher preschool mathematics (OR: 1.51, CI: 1.14, 2.00) and literacy skills (OR: 1.57, CI: 1.10, 2.25) were more likely to attain GCSEs in the respective subject than their term-born counterparts with equal levels of preschool skills. CONCLUSIONS: Preschool academic skills in mathematics and literacy are associated with educational attainment of preterm and term-born individuals in adolescence. Children born prematurely may benefit more from preschool mathematics and literacy skills for academic and educational success into adolescence than term-born individuals.

Genetic correlations between suicide attempts and psychiatric and intermediate phenotypes adjusting for mental disorders.

BACKGROUND: Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders. METHODS: To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes. RESULTS: Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased. CONCLUSIONS: These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.

Childhood behavior problems and adverse economic outcomes: a 30-year population-based study of intergenerational income mobility.

BACKGROUND: The objectives of this study were to (a) assess the associations between early behavioral problems and intergenerational income mobility (i.e., the degree to which income status is transmitted from one generation to the next), (b) verify whether these associations are moderated by child sex, and (c) explore indirect effects of early behavioral problems on income mobility via high school graduation. METHODS: Data were drawn from the Quebec Longitudinal Study of Kindergarten Children (n = 3,020; 49.17% girls). Participants were followed from age 6 to 37 years. Measures included parents' and teachers' ratings of behavioral problems at age 6 years as well as participants' (ages 30-35 years) and their parents' (when participants were aged 10-19 years) income data obtained from tax return records. Regression models were used to predict upward and downward mobility (i.e., increased or decreased income status from one generation to the next) from attention-deficit/hyperactivity problems, conduct/opposition problems, depression/anxiety problems, prosociality, and the quality of children's relationship with their caregiver. Two-way interaction effects between behavioral problems and child sex were examined and indirect effect models including high school graduation as a mediator of these associations were conducted. RESULTS: Despite their higher educational attainment, females had lower incomes and experienced lower upward (but higher downward) income mobility than males. For both females and males, higher levels of attention-deficit/hyperactivity and conduct/opposition problems were associated with decreased odds of upward mobility, whereas higher levels of attention-deficit/hyperactivity were associated with increased odds of downward mobility. Attention-deficit/hyperactivity problems, conduct/opposition problems as well as low prosociality were associated with lower educational attainment (no high school diploma), which in turn was associated with increased odds of downward mobility. CONCLUSIONS: Results highlight the importance of providing intensive support to children with early behavioral problems as a means of improving educational attainment and intergenerational income mobility.

Enabling the examination of long-term mortality trends by educational level for England and Wales in a time-consistent and internationally comparable manner.

BACKGROUND: Studying long-term trends in educational inequalities in health is important for monitoring and policy evaluation. Data issues regarding the allocation of people to educational groups hamper the study and international comparison of educational inequalities in mortality. For the UK, this has been acknowledged, but no satisfactory solution has been proposed. OBJECTIVE: To enable the examination of long-term mortality trends by educational level for England and Wales (E&W) in a time-consistent and internationally comparable manner, we propose and implement an approach to deal with the data issues regarding mortality data by educational level. METHODS: We employed 10-year follow-ups of individuals aged 20+ from the Office for National Statistics Longitudinal Study (ONS-LS), which include education information from each decennial census (1971-2011) linked to individual death records, for a 1% representative sample of the E&W population. We assigned the individual cohort data to single ages and calendar years, and subsequently obtained aggregate all-cause mortality data by education, sex, age (30+), and year (1972-2017). Our data adjustment approach optimised the available education information at the individual level, and adjusts-at the aggregate level-for trend discontinuities related to the identified data issues, and for differences with country-level mortality data for the total population. RESULTS: The approach resulted in (1) a time-consistent and internationally comparable categorisation of educational attainment into the low, middle, and high educated; (2) the adjustment of identified data-quality related discontinuities in the trends over time in the share of personyears and deaths by educational level, and in the crude and the age-standardised death rate by and across educational levels; (3) complete mortality data by education for ONS-LS members aged 30+ in 1972-2017 which aligns with country-level mortality data for the total population; and (4) the estimation of inequality measures using established methods. For those aged 30+ , both absolute and relative educational inequalities in mortality first increased and subsequently decreased. CONCLUSION: We obtained additional insights into long-term trends in educational inequalities in mortality in E&W, and illustrated the potential effects of different data issues. We recommend the use of (part of) the proposed approach in other contexts.

Educational attainment, structural brain reserve and Alzheimer's disease: a Mendelian randomization analysis.

Higher educational attainment is observationally associated with lower risk of Alzheimer's disease. However, the biological mechanisms underpinning this association remain unclear. The protective effect of education on Alzheimer's disease may be mediated via increased brain reserve. We used two-sample Mendelian randomization to explore putative causal relationships between educational attainment, structural brain reserve as proxied by MRI phenotypes and Alzheimer's disease. Summary statistics were obtained from genome-wide association studies of educational attainment (n = 1 131 881), late-onset Alzheimer's disease (35 274 cases, 59 163 controls) and 15 measures of grey or white matter macro- or micro-structure derived from structural or diffusion MRI (nmax = 33 211). We conducted univariable Mendelian randomization analyses to investigate bidirectional associations between (i) educational attainment and Alzheimer's disease; (ii) educational attainment and imaging-derived phenotypes; and (iii) imaging-derived phenotypes and Alzheimer's disease. Multivariable Mendelian randomization was used to assess whether brain structure phenotypes mediated the effect of education on Alzheimer's disease risk. Genetically proxied educational attainment was inversely associated with Alzheimer's disease (odds ratio per standard deviation increase in genetically predicted years of schooling = 0.70, 95% confidence interval 0.60, 0.80). There were positive associations between genetically predicted educational attainment and four cortical metrics (standard deviation units change in imaging phenotype per one standard deviation increase in genetically predicted years of schooling): surface area 0.30 (95% confidence interval 0.20, 0.40); volume 0.29 (95% confidence interval 0.20, 0.37); intrinsic curvature 0.18 (95% confidence interval 0.11, 0.25); local gyrification index 0.21 (95% confidence interval 0.11, 0.31)]; and inverse associations with cortical intracellular volume fraction [-0.09 (95% confidence interval -0.15, -0.03)] and white matter hyperintensities volume [-0.14 (95% confidence interval -0.23, -0.05)]. Genetically proxied levels of surface area, cortical volume and intrinsic curvature were positively associated with educational attainment [standard deviation units change in years of schooling per one standard deviation increase in respective genetically predicted imaging phenotype: 0.13 (95% confidence interval 0.10, 0.16); 0.15 (95% confidence interval 0.11, 0.19) and 0.12 (95% confidence interval 0.04, 0.19)]. We found no evidence of associations between genetically predicted imaging-derived phenotypes and Alzheimer's disease. The inverse association of genetically predicted educational attainment with Alzheimer's disease did not attenuate after adjusting for imaging-derived phenotypes in multivariable analyses. Our results provide support for a protective causal effect of educational attainment on Alzheimer's disease risk, as well as potential bidirectional causal relationships between education and brain macro- and micro-structure. However, we did not find evidence that these structural markers affect risk of Alzheimer's disease. The protective effect of education on Alzheimer's disease may be mediated via other measures of brain reserve not included in the present study, or by alternative mechanisms.

Growing up without health insurance: Evidence from rural China.

This paper examines the long-term effects of health insurance on children's educational attainment in a developing country. Utilizing the county-by-county rollout of the New Rural Cooperative Medical Scheme in rural China, we find that exposure to the health insurance program in early life leads to improved educational attainment in adulthood. Empirical tests suggest that a short-term increase in health care utilization is unlikely to be a potential channel. We provide some evidence for the channel that health insurance reduces household financial burdens and increases household expenditure on children's nutrition.

Effect of Duration of Education on Sexual Activity and the Mediating Role of Illness in Later Life: A Natural Experiment in English Schooling Reform.

This study aimed to examine the effect of increases in the duration of education on sexual activity in later life using the instrumental variable approach. Cross-sectional data were obtained from the English Longitudinal Study of Ageing, Wave 6 (2012/2013) for the analysis. The effect of the duration of education on a binary variable for sexual activity in the past month was examined by two-stage least squares estimation using the 1947 schooling reform as the instrument. A total of 1493 participants were included. The 1947 schooling reform significantly extended the duration of education by a mean of 0.86 years (95% confidence interval (CI), 0.52-1.20; F = 24.70) for men and 0.81 years for women (95% CI, 0.54-1.09; F = 33.82). The second-stage regression showed that an additional year of education increased the probability of having sexual activity in the past month by 0.16 points (95% CI, 0.07-0.25) for men and decreased the probability of having sexual activity in the past month by 0.18 points (95% CI, - 0.30- - 0.05) for women. The causal mediation analysis revealed that long-standing illness mediated the mechanism between education and sexual activity, but the mediational effect was clearly observed only for men: the indirect effect for men was 0.10 (95% CI, 0.01-0.20; the proportion mediated, 78.1%) and for women was - 0.16 (95% CI, - 1.23-0.90; the proportion mediated, 97.8%), respectively. This study confirmed the causal effect of education on sexual activity. However, the effect for men and women was completely opposite.

Risk Factors for Pelvic Organ Prolapse: Wide-Angled Mendelian Randomization Analysis.

INTRODUCTION AND HYPOTHESIS: We hypothesized that some metabolic factors, lifestyle factors, and socioeconomic factors may have a causal effect on pelvic organ prolapse (POP). METHODS: We selected instruments from corresponding genome-wide association studies (GWAS), which identified independent single nucleotide polymorphisms strongly associated with 12 potential risk factors. Summary statistics for POP were derived from two GWAS datasets, serving for discovery and replication stage. The primary analysis involved the use of the inverse-variance weighting mendelian randomization (MR) method, with additional sensitivity MR analyses conducted. RESULTS: The univariable mendelian randomization (UVMR) analysis in both the discovery and replication stage provided evidence for significant causal effects between higher waist-to-hip ratio adjusted for body mass index (WHRadjBMI) levels, lower high-density lipoprotein cholesterol (HDL-C) levels, and lower educational attainment and higher POP risk, as well as a suggestive positive causal effect between triglycerides and POP. The multivariable mendelian randomization (MVMR) analysis showed that only HDL-C among the three blood lipid fractions could reduce the risk of POP. Mediation analysis indicated that HDL-C may partially mediate the effect of WHRadjBMI on POP risk, and the causal effect between educational attainment and POP may be mediated through WHRadjBMI and HDL-C. CONCLUSIONS: Our study's evidence supported a causal relationship between WHRadjBMI, triglycerides, HDL-C, educational attainment, and POP risk. This highlights that clinicians may guide the general female population to control obesity and blood lipid levels to reduce the risk of POP.

The effect of educational attainment on birthrate in Japan: an analysis using the census and the vital statistics from 2000 to 2020.

BACKGROUND: In Japan, difference in birth rates depending on educational attainment has not been investigated. This study aimed to reveal birth rates in Japan depending on the highest level of educational attainment and their trends over the years using nationwide government statistics data. METHODS: Individual-level data from Vital Statistics and the Census from 2000, 2010, and 2020 were used for birth and population data, respectively. Data linkage was conducted for males and females in the Census and fathers and mothers in the Vital Statistics using information about gender, household, nationality, marital status, birth year, birth month, prefecture, and municipality for individuals. The birth rate was calculated by gender, a five-year age group, the highest level of educational attainment achieved, and year. In addition, the slope index of inequality (SII) and relative index of inequality (RII) were calculated to evaluate the degree of inequality in birth rates, depending on the educational attainment. RESULTS: Birth rates were higher in persons with lower educational attainment compared to those with a higher educational attainment among males and females in their twenties, while they tended to be higher in persons with higher educational attainment among those in their thirties and forties. Additionally, an increase in the birth rate from 2000 to 2020 was the largest in university graduates among males aged 25-49 years and women aged 30-49 years, and a decrease in the birth rate was the smallest in university graduates among males and females aged 20-24 years. As a result, SII and RII increased from 2000 to 2020 among males and females in their thirties and forties. CONCLUSIONS: In conclusion, persons with higher educational attainment tended to have a relatively favorable trend in the birth rate compared with persons with lower educational attainment in recent decades. It suggested that enhanced administrative support for individuals with lower educational attainment or lower socioeconomic status may be required to ameliorate the declining birth rate in Japan.

Eight Decades of Educational Assortative Mating: A Research Note.

Recent social and economic trends in the United States, including increasing economic inequality, women's growing educational advantage, and the rise of online dating, have ambiguous implications for patterns of educational homogamy. In this research note, we examine changes in educational assortative mating in the United States over the last eight decades (1940 to 2020) using the U.S. decennial censuses and the American Community Survey, extending and expanding earlier work by Schwartz and Mare. We find that the rise in educational homogamy noted by Schwartz and Mare has not continued. Increases in educational homogamy stalled around 1990 and began reversing in the 2000s. We find a growing tendency for marriages to cross educational boundaries, but a college degree remains the strongest dividing line to intermarriage. A key trend explaining this new pattern is women's increasing tendency to marry men with less education than themselves. If not for this trend, homogamy would have continued increasing until the early 2010s. We also show substantial heterogeneity by race, ethnicity, and nativity and among same- versus different-sex couples.

Evolutionary Trends of Polygenic Scores in European Populations From the Paleolithic to Modern Times.

This study examines the temporal and geographical evolution of polygenic scores (PGSs) across cognitive measures (Educational Attainment [EA], Intelligence Quotient [IQ]), Socioeconomic Status (SES), and psychiatric conditions (Autism Spectrum Disorder [ASD], schizophrenia [SCZ]) in various populations. Our findings indicate positive directional selection for EA, IQ, and SES traits over the past 12,000 years. Schizophrenia and autism, while similar, showed different temporal patterns, aligning with theories suggesting they are psychological opposites. We observed a decline in PGS for neuroticism and depression, likely due to their genetic correlations and pleiotropic effects on intelligence. Significant PGS shifts from the Upper Paleolithic to the Neolithic periods suggest lifestyle and cognitive demand changes, particularly during the Neolithic Revolution. The study supports a mild hypothesis of Gregory Clark's model, showing a noticeable rise in genetic propensities for intelligence, academic achievement and professional status across Europe from the Middle Ages to the present. While latitude strongly influenced height, its impact on schizophrenia and autism was smaller and varied. Contrary to the cold winters theory, the study found no significant correlation between latitude and intelligence.

Adolescent alcohol and cannabis use and early adulthood educational attainment in the 1986 Northern Finland birth cohort study.

BACKGROUND: Heavy alcohol and cannabis use during adolescence have been previously described as risk factors not only for morbidity in adulthood, but also social problems including adversities in educational attainment. Attempts to consider overlapping risk factors and confounders for these associations are needed. METHODS: Using weighted multivariable models, we examined prospective associations between age at first drink (AFD), age at first intoxication (AFI), frequency of alcohol intoxication, as well as self-reported alcohol tolerance (i.e., number of drinks needed for the subjective experience of intoxication), and lifetime cannabis use at age 15/16 years with subsequent educational attainment obtained from comprehensive registers until age 33 in the Northern Finland Birth Cohort 1986 (6,564 individuals, 49.1% male). Confounding variables including sex, family structure (intact vs. non-intact), maternal and paternal education level, behavioural/emotional problems in school at age 7/8 years, having a history of illicit substance use in adolescence, having any psychiatric diagnosis before age 16, and parental psychiatric diagnoses, were adjusted for. RESULTS: In this large birth cohort study with a 17-year follow-up, younger age at first intoxication, higher frequency of alcohol intoxication, and high self-reported alcohol tolerance at age 15/16 years were associated with poorer educational outcomes by the age of 33 years. These associations were evident regardless of potential confounders, including parental education and childhood behavioural/emotional problems. The association between adolescent cannabis use and educational attainment in adulthood was no longer statistically significant after adjusting for confounders including frequency of alcohol intoxication at age 15/16. CONCLUSIONS: Assessments of age of first alcohol intoxication, high self-reported alcohol tolerance and frequency of intoxication during adolescence should be included when implementing screening strategies aimed at identifying adolescents at risk for subsequent social problems.

Adolescent risk behaviours are associated with educational attainment in early adulthood: results from the Raine Study cohort.

BACKGROUND: Higher educational attainment is important for economic wellbeing and associated with better health and longevity. Previous research focused on intelligence, socioeconomic status and mental health or individual risk behaviours as predictors of educational attainment, but the role of multiple domains of adolescent risk behaviours is less clear. This study examined the association between multiple domains of risk behaviour in adolescence and educational attainment by 22 years-of-age. METHODS: Young people (Generation 2, Gen2) and their parents (Generation 1, Gen1) participating in the Raine Study completed questionnaires at years 1, 5, 8, 10 (Gen1 only), 14, 17 (both) and 22 (Gen2 only). The Raine Study is an ongoing longitudinal study initiated in Perth, Western Australia, between 1989 and 1991. The 1,102 Gen2 participants who responded to questions about highest educational attainment were included in this study. The association between Gen2 self-reported risk behaviours (including age at commencement of drinking alcohol, smoking, sexual intercourse and drug use) and educational attainment (defined as self-reported years of completed high school: ≤10, 11, 12 or tertiary education (> 12)) at year 22, after adjusting for mother's age and combined parental education level, participant sex, and family income, educational performance and adolescent mental health, was explored using ordinal regression models and presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Ordinal models suggested that never smoking or starting older than 18 compared with smoking before age 15 (OR 2.02, 95%CI: 1.28-2.14); first drinking alcohol between 15 and 17 years compared with younger than 15 (OR 1.52, 95%CI: 1.08-2.14); and, first sexual intercourse aged ≥ 18 years compared with under 15 (OR 1.67, 95%CI: 1.08-2.57) were associated with higher levels of educational attainment at 22-year follow-up. Additionally, lower ("better") behavioural scores increased the odds of higher levels of attainment. CONCLUSIONS: Absence of health risk behaviours at a younger age or later commencement was associated with higher educational attainment. Evidence-based interventions that address the societal influences underpinning risk behaviours in adolescents may support longer school retention.

Variations in healthcare utilization for mental health problems prior to suicide by socioeconomic status: a Norwegian register-based population study.

BACKGROUND: Suicide poses a major public health challenge, claiming around 650 lives annually in Norway. There is limited understanding of mental healthcare utilization patterns preceding suicide, particularly relating to socioeconomic status (SES). This study analyzes mental health service use among Norwegian citizens aged 20-64 from 2009 to 2021, emphasizing disparities related to SES. METHODS: This is a population-wide registry-based study. We include mental health consultations with both primary and specialist healthcare services, and investigate patterns of service use regarding educational attainment, employment status and income and compare this to the population in general. All suicides in the period (N = 4731) are included in the study. The aim is to investigate potential discrepancies in service use the year and month preceding suicide, seeking to enhance targeted preventive interventions. RESULTS: Our results show significant variations in healthcare use for mental health problems the last year preceding suicide, according to the components of SES, for both men and women. Those with higher education utilize the mental healthcare services prior to suicide to a higher degree than men and women with high school education or less, whereas employed men and men with high income level have significantly lower mental healthcare usage prior to suicide both the last year and month compared to the non-employed men and men with low-income level. Employed women also had a lower mental healthcare usage, whereas the results regarding income are not significant for women. CONCLUSION: Mental healthcare use prior to suicide varies across the SES components. Notably, the SES groups exhibit heterogeneity, with gendered patterns. Targeted interventions for low consultation rates among employed men, and men with high income and lower education are needed, while women, and men in at-risk groups, such as the non-employed and those with low income, demonstrate higher mental healthcare utilization, warranting comprehensive suicide prevention measures.

A longitudinal study of learning difficulties in adolescence and biomarkers of cardiometabolic risk in adulthood: A gendered pathways approach.

OBJECTIVES: Little is known about the relationship between learning difficulties (LD) in adolescence and physical health in adulthood. This study investigates the gender-specific pathways through which LD is longitudinally associated with cardiometabolic risk in adulthood. STUDY DESIGN: We used data from the National Longitudinal Study of Adolescent to Adult Health (N = 11,342). To assess cardiometabolic risk, 11 biomarkers related to cardiovascular functioning, glucose metabolism, lipid metabolism, and inflammation were utilized. METHODS: We first estimated the association between LD in adolescence and cardiometabolic risk in adulthood. Then, we examined whether this association is mediated by educational attainment and body mass index (BMI). Finally, we employed a moderated mediation model to determine whether gender moderates these mediation patterns. RESULTS: LD in adolescence was positively associated with cardiometabolic risk in adulthood (b = 0.165, p < 0.001). LD also predicted lower educational attainment (b = -0.724, p < 0.001) and higher BMI (b = 0.589, p < 0.05). Educational attainment and BMI explained 18 and 25 percent of the positive association between LD and cardiometabolic risk, respectively. A moderated mediation model revealed that indirect effects of LD on cardiometabolic risk via educational attainment and BMI were more pronounced among women than men. CONCLUSION: LD in adolescence is a significant predictor of cardiometabolic risk in adulthood. Interventions focusing on the academic and health behaviors of girls with LD may be effective in improving their adult physical health.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

Obesity and hypertension mediate the effect of education on deep intracerebral hemorrhage: A Mendelian randomization study.

BACKGROUND: Educational attainment (EA) as a stable indicator of socioeconomic status has been confirmed to affect intracerebral hemorrhage (ICH), but the mechanism relating EA and ICH is still unknown. AIM: To explore the causal relationship between EA and ICH through a bidirectional and two-step Mendelian randomization (MR) study. METHODS: Using summary-level Genome-wide Association Study using GWAS data FROM CASES AND CONTROLS of European ancestry, we performed bidirectional and two-step MR analyses to explore the causal relationship between educational attainment and ICH to understand the mediating influence of risk factors in this process. We also carried out subgroup analysis according to the different sites (deep and lobar) of ICH. A set of sensitivity analyses were performed to test valid MR assumptions. RESULTS: Bidirectional MR analysis consistently demonstrated a unidirectional causal effect, revealing that higher EA had a protective influence on ICH. Each additional 1-standard deviation (SD) increase in genetically predicted years of schooling was associated with a reduced risk of all ICH (inverse variance weighted (IVW) OR: 0.381 [95 %CI: 0.264-0.549]), deep ICH (OR: 0.334 [95 %CI: 0.216-0.517]), and lobar ICH (OR: 0.422 [95 %CI: 0.261-0.682]). The mediating effect of EA on all ICH was mediated via systolic blood pressure (SBP) (6.93 % [1.20-13.45 %]) and body mass index (BMI) (17.87 % [3.92-34.64 %]), and the mediating effect of EA on deep ICH was also mediated via SBP (7.85 % [1.55-15.07 %]) and BMI (18.63 % [4.02-36.26 %]). CONCLUSION: This study provides robust genetic evidence for supporting the protective effect of EA on ICH risk, with further evidence that the effect of EA on deep ICH is partially mediated through hypertension and obesity. Further validation is needed to ascertain whether these findings are applicable to other racial or general population groups.