Saskia Selzam

Predicting educational achievement from DNA

A genome-wide polygenic score (GPS), derived from a 2013 genome-wide association study (N=127,000), explained 2% of the variance in total years of education (EduYears). In a follow-up study (N=329,000), a new EduYears GPS explains up to 4%. Here, we tested the association between this latest EduYears GPS and educational achievement scores at ages 7, 12 and 16 in an independent sample of 5825 UK individuals. We found that EduYears GPS explained greater amounts of variance in educational achievement over time, up to 9% at age 16, accounting for 15% of the heritable variance. This is the strongest GPS prediction to date for quantitative behavioral traits. Individuals in the highest and lowest GPS septiles differed by a whole school grade at age 16. Furthermore, EduYears GPS was associated with general cognitive ability (~3.5%) and family socioeconomic status (~7%). There was no evidence of an interaction between EduYears GPS and family socioeconomic status on educational achievement or on general cognitive ability. These results are a harbinger of future widespread use of GPS to predict genetic risk and resilience in the social and behavioral sciences.

Genome-Wide Polygenic Scores Predict Reading Performance throughout the School Years.

ABSTRACT It is now possible to create individual-specific genetic scores, called genome-wide polygenic scores (GPS). We used a GPS for years of education (EduYears) to predict reading performance assessed at UK National Curriculum Key Stages 1 (age 7), 2 (age 12) and 3 (age 14) and on reading tests administered at ages 7 and 12 in a UK sample of 5,825 unrelated individuals. EduYears GPS accounts for up to 5% of the variance in reading performance at age 14. GPS predictions remained significant after accounting for general cognitive ability and family socioeconomic status. Reading performance of children in the lowest and highest 12.5% of the EduYears GPS distribution differed by a mean growth in reading ability of approximately two school years. It seems certain that polygenic scores will be used to predict strengths and weaknesses in education.

The genetic and environmental aetiology of spatial, mathematics and general anxiety

Individuals differ in their level of general anxiety as well as in their level of anxiety towards specific activities, such as mathematics and spatial tasks. Both specific anxieties correlate moderately with general anxiety, but the aetiology of their association remains unexplored. Moreover, the factor structure of spatial anxiety is to date unknown. The present study investigated the factor structure of spatial anxiety, its aetiology, and the origins of its association with general and mathematics anxiety in a sample of 1,464 19-21-year-old twin pairs from the UK representative Twins Early Development Study. Participants reported their general, mathematics and spatial anxiety as part of an online battery of tests. We found that spatial anxiety is a multifactorial construct, including two components: navigation anxiety and rotation/visualization anxiety. All anxiety measures were moderately heritable (30% to 41%), and non-shared environmental factors explained the remaining variance. Multivariate genetic analysis showed that, although some genetic and environmental factors contributed to all anxiety measures, a substantial portion of genetic and non-shared environmental influences were specific to each anxiety construct. This suggests that anxiety is a multifactorial construct phenotypically and aetiologically, highlighting the importance of studying anxiety within specific contexts.

Differences in exam performance between pupils attending selective and non-selective schools mirror the genetic differences between them

On average, students attending selective schools outperform their non-selective counterparts in national exams. These differences are often attributed to value added by the school, as well as factors schools use to select pupils, including ability, achievement and, in cases where schools charge tuition fees or are located in affluent areas, socioeconomic status. However, the possible role of DNA differences between students of different schools types has not yet been considered. We used a UK-representative sample of 4814 genotyped students to investigate exam performance at age 16 and genetic differences between students in three school types: state-funded, non-selective schools (‘non-selective’), state-funded, selective schools (‘grammar’) and private schools, which are selective (‘private’). We created a genome-wide polygenic score (GPS) derived from a genome-wide association study of years of education (EduYears). We found substantial mean genetic differences between students of different school types: students in non-selective schools had lower EduYears GPS compared to those in grammar (d = 0.41) and private schools (d = 0.37). Three times as many students in the top EduYears GPS decile went to a selective school compared to the bottom decile. These results were mirrored in the exam differences between school types. However, once we controlled for factors involved in pupil selection, there were no significant genetic differences between school types, and the variance in exam scores at age 16 explained by school type dropped from 7% to <1%. These results show that genetic and exam differences between school types are primarily due to the heritable characteristics involved in pupil admission.Genetic differences between selective and non-selective schoolsStudents attending selective schools have, on average, more genetic variants associated with educational attainment compared to students attending non-selective schools. A team led by Professor Robert Plomin at King’s College London found that these genetic differences between school types were also mirrored in examination differences. Students attending selective schools were performing a grade higher than their non-selective schooled peers. However, once the researchers statistically accounted for student-level factors, including family socioeconomic status, prior ability and prior achievement, there were no significant genetic differences between students in selective and non-selective schools, and only small examination score differences. This research shows that genetic and exam score differences between selective and non-selective schools are primarily due to the genetically influenced characteristics involved in student admission.

Childhood behaviour problems show the greatest gap between DNA-based and twin heritability

For most complex traits, DNA-based heritability (‘SNP heritability’) is roughly half that of twin-based heritability. A previous report from the Twins Early Development Study suggested that this heritability gap is much greater for childhood behaviour problems than for other domains. If true, this finding is important because SNP heritability, not twin heritability, is the ceiling for genome-wide association studies. With twice the sample size as the previous report, we estimated SNP heritabilities (N up to 4653 unrelated individuals) and compared them with twin heritabilities from the same sample (N up to 4724 twin pairs) for diverse domains of childhood behaviour problems as rated by parents, teachers, and children themselves at ages 12 and 16. For 37 behaviour problem measures, the average twin heritability was 0.52, whereas the average SNP heritability was just 0.06. In contrast, results for cognitive and anthropometric traits were more typical (average twin and SNP heritabilities were 0.58 and 0.28, respectively). Future research should continue to investigate the reasons why SNP heritabilities for childhood behaviour problems are so low compared with twin estimates, and find ways to maximise SNP heritability for genome-wide association studies.

Phenotypic and genetic evidence for a unifactorial structure of spatial abilities

Significance Spatial ability is a strong predictor of several important outcomes, including success in science, technology, engineering, and mathematics (STEM) subjects and careers. This ability is widely believed to be multifactorial, with numerous components and subdomains, such as “mental rotation,” “scanning,” and “mechanical reasoning.” This large twin study allows the genetic and environmental etiology of diverse putative spatial abilities to be explored. The results indicate that this domain is in fact unifactorial, albeit dissociable from general intelligence, suggesting that its structure is much simpler than the sprawling literature suggests. This will aid gene-hunting efforts and allow this ability and its consequences to be examined with greater precision. Spatial abilities encompass several skills differentiable from general cognitive ability (g). Importantly, spatial abilities have been shown to be significant predictors of many life outcomes, even after controlling for g. To date, no studies have analyzed the genetic architecture of diverse spatial abilities using a multivariate approach. We developed “gamified” measures of diverse putative spatial abilities. The battery of 10 tests was administered online to 1,367 twin pairs (age 19–21) from the UK-representative Twins Early Development Study (TEDS). We show that spatial abilities constitute a single factor, both phenotypically and genetically, even after controlling for g. This spatial ability factor is highly heritable (69%). We draw three conclusions: (i) The high heritability of spatial ability makes it a good target for gene-hunting research; (ii) some genes will be specific to spatial ability, independent of g; and (iii) these genes will be associated with all components of spatial ability.

Publication Trends Over 55 Years of Behavioral Genetic Research.

Abstract We document the growth in published papers on behavioral genetics for 5-year intervals from 1960 through 2014. We used 1861 papers published in Behavior Genetics to train our search strategy which, when applied to Ovid PsychINFO, selected more than 45,000 publications. Five trends stand out: (1) the number of behavioral genetic publications has grown enormously; nearly 20,000 papers were published in 2010–2014. (2) The number of human quantitative genetic (QG) publications (e.g., twin and adoption studies) has steadily increased with more than 3000 papers published in 2010–2014. (3) The number of human molecular genetic (MG) publications increased substantially from about 2000 in 2000–2004 to 5000 in 2005–2009 to 9000 in 2010–2014. (4) Nonhuman publications yielded similar trends. (5) Although there has been exponential growth in MG publications, both human and nonhuman QG publications continue to grow. A searchable resource of this corpus of behavioral genetic papers is freely available online at http://www.teds.ac.uk/public_datasets.html and will be updated annually.

Genetic influence on social outcomes during and after the Soviet era in Estonia

The aetiology of individual differences in educational attainment and occupational status includes genetic as well as environmental factors1–5 and can change as societies change3,6,7. The extent of genetic influence on these social outcomes can be viewed as an index of success in achieving meritocratic values of equality of opportunity by rewarding talent and hard work, which are to a large extent influenced by genetic factors, rather than rewarding environmentally driven privilege. To the extent that the end of the Soviet Union and the independence of Estonia led to an increase in meritocratic selection of individuals in education and occupation, genetic influence should be higher in the post-Soviet era than in the Soviet era. Here we confirmed this hypothesis: DNA differences (single-nucleotide polymorphisms) explained twice as much variance in educational attainment and occupational status in the post-Soviet era compared with the Soviet era in both polygenic score analyses and single-nucleotide polymorphism heritability analyses of 12,500 Estonians. Our results demonstrate a change in the extent of genetic influence in the same population following a massive and abrupt social change—in this case, the shift from a communist to a capitalist society.An analysis of genetic influences on educational attainment and occupation in pre- versus post-Soviet-era Estonia shows that genetics has a much greater influence on social outcomes in a meritocratic society.

Rotation is visualisation, 3D is 2D: using a novel measure to investigate the genetics of spatial ability.

Spatial abilities–defined broadly as the capacity to manipulate mental representations of objects and the relations between them–have been studied widely, but with little agreement reached concerning their nature or structure. Two major putative spatial abilities are “mental rotation” (rotating mental models) and “visualisation” (complex manipulations, such as identifying objects from incomplete information), but inconsistent findings have been presented regarding their relationship to one another. Similarly inconsistent findings have been reported for the relationship between two- and three-dimensional stimuli. Behavioural genetic methods offer a largely untapped means to investigate such relationships. 1,265 twin pairs from the Twins Early Development Study completed the novel “Bricks” test battery, designed to tap these abilities in isolation. The results suggest substantial genetic influence unique to spatial ability as a whole, but indicate that dissociations between the more specific constructs (rotation and visualisation, in 2D and 3D) disappear when tested under identical conditions: they are highly correlated phenotypically, perfectly correlated genetically (indicating that the same genetic influences underpin performance), and are related similarly to other abilities. This has important implications for the structure of spatial ability, suggesting that the proliferation of apparent sub-domains may sometimes reflect idiosyncratic tasks rather than meaningful dissociations.

Evidence for gene-environment correlation in child feeding: Links between common genetic variation for BMI in children and parental feeding practices

The parental feeding practices (PFPs) of excessive restriction of food intake (‘restriction’) and pressure to increase food consumption (‘pressure’) have been argued to causally influence child weight in opposite directions (high restriction causing overweight; high pressure causing underweight). However child weight could also ‘elicit’ PFPs. A novel approach is to investigate gene-environment correlation between child genetic influences on BMI and PFPs. Genome-wide polygenic scores (GPS) combining BMI-associated variants were created for 10,346 children (including 3,320 DZ twin pairs) from the Twins Early Development Study using results from an independent genome-wide association study meta-analysis. Parental ‘restriction’ and ‘pressure’ were assessed using the Child Feeding Questionnaire. Child BMI standard deviation scores (BMI-SDS) were calculated from children’s height and weight at age 10. Linear regression and fixed family effect models were used to test between-(n=4,445 individuals) and within-family (n=2,164 DZ pairs) associations between the GPS and PFPs. In addition, we performed multivariate twin analyses (n=4,375 twin pairs) to estimate the heritabilities of PFPs and the genetic correlations between BMI-SDS and PFPs. The GPS was correlated with BMI-SDS (β=0.20, p=2.41×10-38). Consistent with the gene-environment correlation hypothesis, child BMI GPS was positively associated with ‘restriction’ (β=0.05, p=4.19×10-4), and negatively associated with ‘pressure’ (β=-0.08, p=2.70×10-7). These results remained consistent after controlling for parental BMI, and after controlling for overall family contributions (within-family analyses). Heritabilities for ‘restriction’ (43% [40-47%]) and ‘pressure’ (54% [50-59%]) were moderate-to-high. Twin-based genetic correlations were moderate and positive between BMI-SDS and ‘restriction’ (rA=0.28 [0.23-0.32]), and substantial and negative between BMI-SDS and ‘pressure’ (rA=-0.48 [-0.52 --0.44]. Results suggest that the degree to which parents limit or encourage children’s food intake is partly influenced by children’s genetic predispositions to higher or lower BMI. These findings point to an evocative gene-environment correlation in which heritable characteristics in the child elicit parental feeding behaviour. Author Summary It is widely believed that parents influence their child’s BMI via certain feeding practices. For example, rigid restriction has been argued to cause overweight, and pressuring to eat to cause underweight. However, recent longitudinal research has not supported this model. An alternative hypothesis is that child BMI, which has a strong genetic basis, evokes parental feeding practices (‘gene-environment correlation’). To test this, we applied two genetic methods in a large sample of 10-year-old children from the Twins Early Development Study: a polygenic score analysis (DNA-based score of common genetic variants robustly associated with BMI in genome-wide meta-analyses), and a twin analysis (comparing resemblance between identical and non-identical twin pairs). Polygenic scores correlated positively with parental restriction of food intake (‘restriction’; β=0.05, p=4.19×10-4), and negatively with parental pressure to increase food intake (‘pressure’; β=-0.08, p=2.70×10-7). Associations were unchanged after controlling for all genetic and environmental effects shared within families. Results from twin analyses were consistent. ‘Restriction’ (43%) and ‘pressure’ (54%) were substantially heritable, and a positive genetic correlation between child BMI and ‘restriction’ (rA=0.28), and negative genetic correlation between child BMI and ‘pressure’ (rA=-0.48) emerged. These findings challenge the prevailing view that parental behaviours are the sole cause of child BMI by supporting an alternate hypothesis that child BMI also causes parental feeding behaviour.