Hamshere, M.

Heron, J.

Martin, J.

Smith, G.

St Pourcain, B.

Stergiakouli, E.

Thapar, A.

Timpson, N.

English

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2015 World Congress of Psychiatric GeneticsPolygenic Risk Scores for Clinical ADHD are Associated withImpaired Educational Achievement and Lower IQ in Children andAdults from the General PopulationTopic ADHDSubmitter Evie StergiakouliSUBMISSION DETAILSBackground High levels of ADHD symptoms during early childhood carry risk of worse academicperformance at age 16 (Washbrook et al. 2013) and can impact on employment and earnings inadulthood (Fletcher 2013). Polygenic score analysis was used to show that common risk alleles forclinical ADHD contribute to the risk of having higher ADHD symptoms in the general population(Martin et al. 2014). We used polygenic risk score analysis to investigate the contribution ofcommon risk variants for clinical ADHD on educational performance and IQ in the generalpopulation.Methods Polygenic risk scores were calculated for Avon Longitudinal Study of Parents and Children(ALSPAC) participants (Boyd et al. 2013, Fraser et al. 2013) (8,365 children and 8,340 mothers)based on the results of a discovery sample, a genome-wide association study of 727 cases withADHD diagnosis and 5,081 controls from Cardiff University (Stergiakouli et al. 2012) and tested forassociation with IQ and educational outcomes in adolescence and adulthood. The QC proceduresand ascertainment of the target and discovery samples have been described in detail previously(Stergiakouli et al. 2012, Stergiakouli et al. 2014). Educational achievement was assessed usingresults from Key Stage 3 national tests, externally marked GCSE examinations and the probabilityof sitting Key Stage 5 examinations in 6,385 children from ALSPAC. Mothers’ educationalachievement was measured by self-reported highest qualification obtained. We also performedexploratory mediation analysis of the relationship between ADHD polygenic risk scores and ADHDsymptoms with educational and cognitive outcomes in ALSPAC children.Results ADHD polygenic scores on the children were associated with worst educational outcomesat the 3 time points tested; Key stage 3 scores (β=-1.4 (-2 to -0.8), p=2.3 x 10-6), capped GCSEpoints (β=-4 (-6.1 to -1.9), p=1.8 x 10-4) and reduced probability of sitting Key Stage 5examinations (OR=0.9 (0.88 to 0.97), p=0.001). They were also associated with lower IQ scores atage 15.5 (β=-0.8 (-1.2 to -0.4), p=2.4x10-4). Maternal ADHD polygenic scores were associated withlower maternal IQ (β=-0.6 (-1.2 to -0.1), p=0.03) and lower maternal educational achievement(β=-0.09 (-0.1 to -0.06), p=0.005). Mediation analysis indicated that the association of ADHDpolygenic risk score with educational outcomes was mediated substantially but not entirely by IQand to a lesser extent by earlier levels of ADHD.Discussion Using a population-based sample, we demonstrated that genetic risk for clinicaldisorder is relevant for children and adults from the general population irrespective of whether theyreach diagnostic criteria for the disorder. High genetic loading for clinical ADHD is associated withincreased risk of educational under-achievement and lower IQ in ALSPAC. Our study highlights the12015 World Congress of Psychiatric Geneticspotential of population samples for investigating the full distribution of psychiatric and cognitivetraits in large numbers of individuals without a disorder diagnosis. Further investigation is requiredto determine if children with subthreshold ADHD symptoms would benefit from appropriateinterventions and support to achieve their potential in education.Co-Authors* Presenting AuthorFirst Name Last Name Affiliation E-mailEvie * Stergiakouli * MRC IntegrativeEpidemiology Unit (IEU) atthe University of Bristol,Bristol, UKe.stergiakouli@bristol.ac.ukJoanna Martin MRC Centre forNeuropsychiatric Geneticsand Genomics, CardiffUniversity, Cardiff, UKmartinjm1@cardiff.ac.ukMarian Hamshere MRC Centre forNeuropsychiatric Geneticsand Genomics, CardiffUniversity, Cardiff, UKhamshereml@cardiff.ac.ukJon Heron School of Social andCommunity Medicine,University of Bristol,Bristol, UKjon.heron@bristol.ac.ukBeate St Pourcain MRC IntegrativeEpidemiology Unit (IEU) atthe University of Bristol,Bristol, UK; School of Oraland Dental Sciences,University of Bristol,Bristol, UKbeate.stpourcain@bristol.ac.ukNicholas Timpson MRC IntegrativeEpidemiology Unit at theUniversity of Bristol,Bristol, UKn.j.timpson@bristol.ac.uk22015 World Congress of Psychiatric GeneticsAnita Thapar MRC Centre forNeuropsychiatric Geneticsand Genomics, CardiffUniversity, Cardiff, UKthapar@cf.ac.ukGeorge Davey Smith MRC IntegrativeEpidemiology Unit at theUniversity of Bristol,Bristol, UKkz.davey-smith@bristol.ac.ukHugh Gurling Award NoDISCLOSUREFinancial Relationships I have no real or apparent conflicts of interest to disclose.Investigational or off-label use of a product NONEResearch Support The MRC IEU is supported by the Medical Research Council and the Universityof Bristol (grant code MC_UU_12013/1-9) and the MRC Centre for Neuropsychiatric Genetics andGenomics is supported by the Medical Research Council, the Wellcome Trust and Cardiff University(grant code 079711/Z/06/Z).Human or Animal Ethics Board Review YesSignature Evie Sterg3

Polygenic risk scores for clinical ADHD are associated with impaired educational achievement and lower IQ in children and adults from the general population

Polygenic risk scores for clinical ADHD are associated with impaired educational achievement and lower IQ in children and adults from the general population

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