Polygenic Scores For Educational Attainment Research Articles

Parental education and children’s depression, anxiety, and ADHD traits, a within-family study in MoBa

Children born to parents with fewer years of education are more likely to have depression, anxiety, and attention-deficit hyperactivity disorder (ADHD), but it is unclear to what extent these associations are causal. We estimated the effect of parents’ educational attainment on children’s depressive, anxiety, and ADHD traits at age 8 years, in a sample of 40,879 Norwegian children born in 1998–2009 and their parents. We used within-family Mendelian randomization, which employs genetic variants as instrumental variables, and controlled for direct genetic effects by adjusting for children’s polygenic indexes. We found little evidence that mothers’ or fathers’ educational attainment independently affected children’s depressive, anxiety, or ADHD traits. However, children’s own polygenic scores for educational attainment were independently and negatively associated with these traits. Results suggest that differences in these traits according to parents’ education may reflect direct genetic effects more than genetic nurture. Consequences of social disadvantage for children’s mental health may however be more visible in samples with more socioeconomic variation, or contexts with larger socioeconomic disparities than present-day Norway. Further research is required in populations with more educational and economic inequality and in other age groups.

Schoolhouse risk: Can we mitigate the polygenic Pygmalion effect?

BackgroundAlthough limited in predictive accuracy, polygenic scores (PGS) for educational outcomes are currently available to the public via direct-to-consumer genetic testing companies. Further, there is a growing movement to apply PGS in educational settings via ‘precision education.’ Prior scholarship highlights the potentially negative impacts of such applications, as disappointing results may give rise a “polygenic Pygmalion effect.” In this paper two studies were conducted to identify factors that may mitigate or exacerbate negative impacts of PGS. MethodsTwo studies were conducted. In each, 1188 students were randomized to one of four conditions: Low-percentile polygenic score for educational attainment (EA-PGS), Low EA-PGS + Mitigating information, Low EA-PGS + Exacerbating information, or Control. Regression analyses were used to examine differences between conditions. ResultsIn Study 1, participants randomized to Control reported significantly higher on the Rosenberg Self-Esteem Scale (RSES), Competence Scale (CS), Academic Efficacy Scale (AES) and Educational Potential Scale (EPS). CS was significantly higher in the Low EA-PGS + Mitigating information condition. CS and AES were significantly lower in the Low EA-PGS + Exacerbating information condition compared to the Low EA-PGS + Mitigating information condition. In Study 2, participants randomized to Control reported significantly higher CS and AES. Pairwise comparisons did not show significant differences in CS and AES. Follow-up pairwise comparisons using Tukey P-value correction did not find significant associations between non-control conditions. ConclusionThese studies replicated the polygenic Pygmalion effect yet were insufficiently powered to detect significant effects of mitigating contextual information. Regardless of contextual information, disappointing EA-PGS results were significantly associated with lower assessments of self-esteem, competence, academic efficacy, and educational potential.

Genetic modifiers of rare variants in monogenic developmental disorder loci

Rare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DDs) and have also been shown to cause milder subclinical phenotypes in population cohorts. Here, we show that carrying multiple (2−5) rare damaging variants across 599 dominant DD genes has an additive adverse effect on numerous cognitive and socioeconomic traits in UK Biobank, which can be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Phenotypic deviators from expected EA-PGS could be partly explained by the enrichment or depletion of rare DD variants. Among carriers of rare DD variants, those with a DD-related clinical diagnosis had a substantially lower EA-PGS and more severe phenotype than those without a clinical diagnosis. Our results suggest that the overall burden of both rare and common variants can modify the expressivity of a phenotype, which may then influence whether an individual reaches the threshold for clinical disease.

Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

Polygenic Variation Underlying Educational Attainment and Attention-Deficit/Hyperactivity Disorder Indexes Behavior Ratings of Executive Functions in Child Psychiatry Outpatients

Objective: We leveraged common genetic variation underlying ADHD, educational attainment (EA) and cognition (COG) to understand the nature of the Behavior Rating Inventory for Executive Functions (BRIEF) and its relationship to academic functioning. Method: Participants were 991 youth, ages 7 to 17, consecutively referred for neuropsychiatric evaluation. Polygenic scores (PGS) for ADHD, EA, and COG were related to the BRIEF using regression analyses. Structural equation models were used to examine the associations between the PGS, BRIEF and academic outcomes (math, reading, and special education services [EDPLAN]). Results: After modeling the PGS together, only the EA and ADHD PGS significantly associated with the BRIEF. The BRIEF partially mediated the relationships between EA PGS with math and EDPLAN and fully mediated the relationship between ADHD PGS and EDPLAN. Conclusion: Genetic data extend evidence that the BRIEF measures a construct relevant to educational success that differs from what is indexed by cognitive testing.

Polygenic risk for depression and anterior and posterior hippocampal volume in children and adolescents

BackgroundDepression has frequently been associated with smaller hippocampal volume. The hippocampus varies in function along its anterior-posterior axis, with the anterior hippocampus more strongly associated with stress and emotion processing. The goals of this study were to examine the associations among parental history of anxiety/depression, polygenic risk scores for depression (PGS-DEP), and anterior and posterior hippocampal volumes in children and adolescents. To examine specificity to PGS-DEP, we examined associations of educational attainment polygenic scores (PGS-EA) with anterior and posterior hippocampal volume. MethodsParticipants were 350 3- to 21-year-olds (46 % female). PGS-DEP and PGS-EA were computed based on recent, large-scale genome-wide association studies. High-resolution, T1-weighted magnetic resonance imaging (MRI) data were acquired, and a semi-automated approach was used to segment the hippocampus into anterior and posterior subregions. ResultsChildren and adolescents with higher polygenic risk for depression were more likely to have a parent with a history of anxiety/depression. Higher polygenic risk for depression was significantly associated with smaller anterior but not posterior hippocampal volume. PGS-EA was not associated with anterior or posterior hippocampal volumes. LimitationsParticipants in these analyses were all of European ancestry. ConclusionsPolygenic risk for depression may lead to smaller anterior but not posterior hippocampal volume in children and adolescents, and there may be specificity of these effects to PGS-DEP rather than PGS-EA. These findings may inform the earlier identification of those in need of support and the design of more effective, personalized treatment strategies.Declarations of interest: none. Declarations of interestNone.

Identification of loci involved in childhood visual acuity and associations with cognitive skills and educational attainment.

Visual acuity significantly contributes to quality of life. Deficits in childhood are associated with reading difficulties, which can have detrimental effects on education outcomes. In adults, it has been observed that vision defects such as myopia are associated with higher educational attainment (EA). Understanding genetic factors contributing to visual acuity could help to dissect its links with cognitive skills, neurodevelopmental conditions, and education. We examined associations between distance visual acuity, cognitive measures including school grades, and neurodevelopmental conditions in a longitudinal cohort of British children (ALSPAC, n = 6807, M age = 11.8). We performed a genome-wide association study (GWAS, n = 5571) on visual acuity and tested for genetic associations with relevant phenotypes using polygenic scores (PGS) and genetic correlation analyses. Visual acuity was associated with better cognitive performance and school grades, and reduced in individuals with reading difficulties compared to controls. GWAS revealed genetic associations at the NPLOC4 locus and highlighted other genes involved in sensory function. In line with positive genetic correlations between visual acuity and cognitive measures, EA PGS were positively associated with visual acuity, while there was a less robust negative association with myopia PGS. In conclusion, increased visual acuity is associated with a range of positive outcomes, including better school grades. Our results suggest an association between a higher EA PGS and slightly increased visual acuity in childhood. This could indicate gene-environment correlation, in which environmental exposures linked to higher EA might have detrimental effects on vision offsetting the initial positive effect.

The production of within-family inequality: Insights and implications of integrating genetic data.

The integration of genetic data within large-scale social and health surveys provides new opportunities to test long-standing theories of parental investments in children and within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments of young children's abilities that are uncontaminated by parental investments, and family-based samples allow indirect tests of whether children's abilities are reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank to test whether the relative ranking of siblings' polygenic scores for educational attainment is consequential for actual attainments. We find evidence consistent with compensatory processes, on average, where the association between genotype and phenotype of educational attainment is reduced by over 20% for the higher-ranked sibling compared to the lower-ranked sibling. These effects are most pronounced in high socioeconomic status areas. We find no evidence that similar processes hold in the case of height or for relatives who are not full biological siblings (e.g. cousins). Our results provide a new use of polygenic scores to understand processes that generate within-family inequalities and also suggest important caveats to causal interpretations the effects of polygenic scores using sibling difference designs. Future work should seek to replicate these findings in other data and contexts.

Multivariate analyses of molecular genetic associations between childhood psychopathology and adult mood disorders and related traits.

Ubiquitous associations have been detected between different types of childhood psychopathology and polygenic risk scores based on adult psychiatric disorders and related adult outcomes, indicating that genetic factors partly explain the association between childhood psychopathology and adult outcomes. However, these analyses in general do not take into account the correlations between the adult trait and disorder polygenic risk scores. This study aimed to further clarify the influence of genetic factors on associations between childhood psychopathology and adult outcomes by accounting for these correlations. Using a multivariate multivariable regression, we analyzed associations of childhood attention-deficit/hyperactivity disorder (ADHD), internalizing, and social problems, with polygenic scores (PGS) of adult disorders and traits including major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI), derived for 20,539 children aged 8.5-10.5 years. After correcting for correlations between the adult phenotypes, major depression PGS were associated with all three childhood traits, that is, ADHD, internalizing, and social problems. In addition, BMI PGS were associated with ADHD symptoms and social problems, while neuroticism PGS were only associated with internalizing problems and educational attainment PGS were only associated with ADHD symptoms. PGS of bipolar disorder, subjective well-being, and insomnia were not associated with any childhood traits. Our findings suggest that associations between childhood psychopathology and adult traits like insomnia and subjective well-being may be primarily driven by genetic factors that influence adult major depression. Additionally, specific childhood phenotypes are genetically associated with educational attainment, BMI and neuroticism.

The anti-Wilson effect: The decrease in heritability of general cognitive ability, as proxied by polygenic expressivity, with advanced age

Polygenic expressivity on general cognitive ability (GCA) declines with increasing age in a cohort of 5,236 individuals born from 1916 to 1955 sourced from the Health and Retirement Study. The effect is detected with a two-way interaction between participant birth year and an educational attainment polygenic score (PGS) predicting GCA, and is robust to controlling hierarchically for population stratification and the main effects of the PGS and participant birth year, in addition to interactions involving all of these factors. The effect can also be recovered using the continuous parameter estimation model, an alternative method for detecting moderation/interaction effects. These findings suggest that the true relationship between the heritability of GCA and age is (likely) best captured by a negative quadratic model, with the Wilson effect beginning to give way to the anti-Wilson effect in the 50–69 years age range. This anti-Wilson effect is likely a function of broad age-related cognitive decline (which is also found in the current study), reflecting reduced phenotypic system integrity associated with accumulating somatic mutations and phenotypic insults. These likely depress cognitive performance (e.g., accuracy and processing efficiency), causing a reduction in apparent heritability due to increased error.

Educational Attainment Polygenic Scores: Examining Evidence for Gene-Environment Interplay with Adolescent Alcohol, Tobacco and Cannabis Use.

Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene-environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age², cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene-environment correlation with adolescent alcohol use at all PGS thresholds (<i>p</i>s&lt;.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (Δ<i>R</i>² ranged from 0.5% to 1.1%). The positive gene-environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors.

Associations between brain imaging and polygenic scores of mental health and educational attainment in children aged 9–11

Psychiatric disorders are highly heritable and polygenic, and many have their peak onset in late childhood and adolescence, a period of tremendous changes. Although the neurodevelopmental antecedents of mental illness are widely acknowledged, research in youth population cohorts is still scarce, preventing our progress towards the early characterization of these disorders. We included 7,124 children (9–11 years old) from the Adolescent Brain and Cognitive Development Study to map the associations of structural and diffusion brain imaging with common genetic variants and polygenic scores for psychiatric disorders and educational attainment. We used principal component analysis to derive imaging components, and calculated their heritability. We then assessed the relationship of imaging components with genetic and clinical psychiatric risk with univariate models and Canonical correlation analysis (CCA). Most imaging components had moderate heritability. Univariate models showed limited evidence and small associations of polygenic scores with brain structure at this age. CCA revealed two significant modes of covariation. The first mode linked higher polygenic scores for educational attainment with less externalizing problems and larger surface area. The second mode related higher polygenic scores for schizophrenia, bipolar disorder, and autism spectrum disorder to higher global cortical thickness, smaller white matter volumes of the fornix and cingulum, larger medial occipital surface area and smaller surface area of lateral and medial temporal regions. While cross-validation suggested limited generalizability, our results highlight the potential of multivariate models to better understand the transdiagnostic and distributed relationships between mental health and brain structure in late childhood.

Gene–environment correlations across geographic regions affect genome-wide association studies

Gene–environment correlations affect associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here we showed in up to 43,516 British siblings that educational attainment polygenic scores capture gene–environment correlations, and that migration extends these gene–environment correlations beyond the family to broader geographic regions. We then ran GWASs on 56 complex traits in up to 254,387 British individuals. Controlling for geographic regions significantly decreased the heritability for socioeconomic status (SES)-related traits, most strongly for educational attainment and income. For most traits, controlling for regions significantly reduced genetic correlations with educational attainment and income, most significantly for body mass index/body fat, sedentary behavior and substance use, consistent with gene–environment correlations related to regional socio-economic differences. The effects of controlling for birthplace and current address suggest both passive and active sources of gene–environment correlations. Our results show that the geographic clustering of DNA and SES introduces gene–environment correlations that affect GWAS results.

Educational attainment polygenic scores, socioeconomic factors, and cortical structure in children and adolescents.

Genome‐wide polygenic scores for educational attainment (PGS‐EA) and socioeconomic factors, which are correlated with each other, have been consistently associated with academic achievement and general cognitive ability in children and adolescents. Yet, the independent associations of PGS‐EA and socioeconomic factors with specific underlying factors at the neural and neurocognitive levels are not well understood. The main goals of this study were to examine the unique contributions of PGS‐EA and parental education to cortical structure and neurocognitive skills in children and adolescents, and the associations among PGS‐EA, cortical structure, and neurocognitive skills. Participants were typically developing 3‐ to 21‐year‐olds (53% male; N = 391). High‐resolution, T1‐weighted magnetic resonance imaging data were acquired, and cortical thickness (CT) and surface area (SA) were measured. PGS‐EA were computed based on the EA3 genome‐wide association study of educational attainment. Participants completed executive function, vocabulary, and episodic memory tasks. Higher PGS‐EA and parental education were independently and significantly associated with greater total SA and vocabulary. Higher PGS‐EA was significantly associated with greater SA in the left medial orbitofrontal gyrus and inferior frontal gyrus, which was associated with higher executive function. Higher parental education was significantly associated with greater SA in the left parahippocampal gyrus after accounting for PGS‐EA and total brain volume. These findings suggest that education‐linked genetics may influence SA in frontal regions, leading to variability in executive function. Associations of parental education with cortical structure in children and adolescents remained significant after controlling for PGS‐EA, a source of genetic confounding.

Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population

The complexity of autism’s phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. In N = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively. Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found—surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS. Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).

Investigating how the accuracy of teacher expectations of pupil performance relate to socioeconomic and genetic factors

Teacher expectations of pupil ability can influence educational progression, impacting subsequent streaming and exam level. Systematic discrepancies between teacher expectations of pupil achievement may therefore have a detrimental effect on children’s education. Associations between socioeconomic and demographic factors with teacher expectation accuracy have been demonstrated, but it is not known how teacher expectations of achievement may relate to genetic factors. We investigated these relationships using nationally standardized exam results at ages 11 and 14 from a UK longitudinal cohort study. We found that teacher expectation of achievement was strongly correlated with educational test scores. Furthermore, the accuracy of teacher expectation was patterned by pupil socioeconomic background but not teacher characteristics. The accuracy of teacher expectation related to pupil’s genetic liability to education as captured by a polygenic score for educational attainment. Despite correlation with the polygenic score, we found no strong evidence for genomewide SNP heritability in teacher reporting accuracy.

A multi-informant and multi-polygenic approach to understanding predictors of peer victimisation in childhood and adolescence.

Peer victimisation is a prevalent occurrence in childhood and adolescence and can often have long-lasting consequences. Previous research using polygenic scores (PGSs) have revealed various genetic vulnerabilities as predictive of victimisation in childhood. However, findings were based on self-report and may therefore be influenced by varying self-perceptions. Previous investigations also focused on average victimisation across childhood, and thus do not capture variability in polygenic predictability over time. The present study, therefore, aimed to investigate associations between PGSs and victimisation using separate and combined reports from teachers and peers in childhood, as well as self-reports in later adolescence to explore trajectories of victimisation. Data were derived from the Quebec Newborn Twin Study. Participants were assessed for victimisation using self-reports from 7 to 17years and using teacher ratings and peer nominations between 7 and 10years (n=536). Ten PGSs related to mental health, cognitive abilities and physical traits were examined as possible predictors of victimisation using linear regressions and growth curve models. Findings revealed that PGSs associated with victimisation are consistent across informants, but to varying extent according to estimated effect sizes. Self-reported victimisation was predicted by PGSs related to mental health, while PGSs related to cognitive and physical traits had larger effect estimates when predicting teacher- and peer-reported victimisation. The PGS for educational attainment was consistently negatively associated with victimisation across informants, producing the largest effect estimates (β=-.104, 95% CI=-.169 to -.039) when predicting a multi-informant measure of victimisation. No PGS predicted changes in victimisation over time. While the PGS for educational attainment is a robust predictor of victimisation, many PGSs are differentially associated with victimisation depending on the informant. Such findings highlight the need to pay close attention to the phenotypic assessment of victimisation, and show that using multiple informants can both strengthen and provide unique insight into how associations may occur.

In Italy, North-South Differences in Student Performance Are Mirrored by Differences in Polygenic Scores for Educational Attainment

In Italy, North-South Differences in Student Performance Are Mirrored by Differences in Polygenic Scores for Educational Attainment

Higher educational attainment is associated with longer telomeres in midlife: Evidence from sibling comparisons in the UK Biobank

Prior studies have established that higher educational attainment is associated with a longer telomere length (TL), a marker of cellular aging. However, it is unclear whether extant associations are causal, since they are likely confounded by unobserved genetic, early-life and family background factors that are correlated with education and TL. We leverage sibling differences in TL, education and measured genetics (polygenic scores for educational attainment and TL) to estimate associations between educational attainment and TL in midlife for European ancestry individuals in the UK Biobank, while controlling for unobserved confounders shared by siblings. After controlling for genetics and shared background between siblings, we find suggestive evidence that high school graduates have longer telomeres than high school dropouts, but we find no differences in TL between high school dropouts and college graduates.

The Wisconsin Longitudinal Study: New Cognitive, Genetic, Biological, and Social Data and a Diversifying Sample

The Wisconsin Longitudinal Study (WLS) has followed a sample of one in three Wisconsin high school graduates from the class of 1957 for over 64 years, making it an excellent data source for researchers interested in linking early and midlife characteristics to a wide range of later-life outcomes. The WLS is unique among major studies of aging cohorts for its duration of follow up, the inclusion of siblings, and the combination of rich social and health information. This symposium will provide an overview of the WLS, describe recent data collection and linkages, and introduce ongoing efforts to diversify the educational and racial/ethnic composition of the study sample. WLS data cover nearly every aspect of the participants’ lives from early life socioeconomic background, schooling, family, and work, to physical and mental health, social participation, civic engagement, well-being, and cognition. The study is linked to administrative data including Medicare records, Social Security records, mortality records, and resource data on primary and secondary schools attended by participants as well as characteristics of their employers, industries, and communities of residence. Recent data collection efforts have generated a wealth of new biological and cognitive information, including genetic data collected from saliva and blood samples, measures of the gut microbiome, and derived polygenic scores for educational attainment, cognitive performance, depression, and subjective well-being. The currently-fielding ILIAD effort is implementing rigorous AD diagnostic protocols to track the progression of dementia across cognitive phenotypes. The symposium will conclude with practical information on accessing and using the data.