Evans, D.

Martin, J.

Robinson, E.

Ronald, A.

Skuse, D.

Smith, G.

St Pourcain, B.

Stergiakouli, E.

Susan, R.

Thapar, A.

Timpson, N.

English

MPG.PuRe

2015 World Congress of Psychiatric GeneticsGenetic Links between Social-Communication Traits, ADHD Traitsand Clinical ADHD During DevelopmentTopic ADHDSubmitter Beate St PourcainSUBMISSION DETAILSBackground There is high comorbidity between autism spectrum disorders (ASD) and attentiondeficit hyperactivity disorder (ADHD) and population-based studies have shown complex symptomco-occurrence. At least some of these links are due to overlapping genetic influences. Whiletrajectories for ASD symptoms are relatively stable during development however, trajectories forADHD symptoms are more variable and only sometimes persistent into adulthood. This study wasperformed to investigate genetic links between ASD traits and ADHD traits in the generalpopulation, and ADHD disorder in a clinical sample, from a developmental perspective.Methods We studied social-communication difficulties (at ages 8, 11, 14 and 17 years;mother-reported Social and Communication Disorders Checklist, SCDC) and combinedhyperactive-impulsive/inattentive symptoms (ages 7, 8, 10, 12, 13 and 17 years; mother-reportedStrength and Difficulties Questionnaire, SDQ) in ≤ 5,680 children from a UK population-based birthcohort (Avon Longitudinal Study of Parents and Children, ALSPAC). Traits were rank transformed tonormality, and genome-wide analyses carried out using 1000G imputed data in ALSPAC children.Genetic correlations within ALSPAC were assessed with Genome-Wide Complex Trait Analysis(GCTA). Genetic links between these traits and clinical ADHD (2,096 trios, 3,470 cases, 11,494controls, based on available ADHD PGC GWAS summary statistics) were analysed using LD ScoreRegression (LDSC).Results There were genetic links between social-communication difficulties and ADHD traitsthroughout development, despite considerable variation in GCTA heritability (SCDC GCTA-h2: 0.08to 0.45; SDQ GCTA-h2: 0.11 to 0.28). Irrespective of when social-communication difficulties wereassessed, we observed, on average, smaller genetic correlations between these phenotypes andADHD traits at 10 to 12 years, ranging between 0.10 to 0.56 (Pmin=0.02), while ADHD traits beforeand after this age showed stronger links, ranging between 0.41 to 1 (Pmin=8.0*10-5).We also found genetic correlations between clinical ADHD and social-communication difficulties at8, 11 and 14 years, ranging between 0.33 and 0.75 (Pmin<0.027), with some attenuation at 17years (r=0.22, P=0.14). Findings were confirmed through polygenic score analysis in an ADHD PGCsubsample  (725 cases, 5081 controls; adjusted-R2≤0.19%, P≥0.004), based on a GWAS ofsocial-communication difficulties in ALSPAC. As a positive control, we also confirmed genetic correlations between clinical ADHD andSDQ-assessed ADHD traits throughout development, ranging between 0.49 and 0.86 (all P<0.05).Discussion In summary, our findings support shared common genetic influences between12015 World Congress of Psychiatric Geneticssocial-communication difficulties and ADHD traits in the general population, as well asclinically-diagnosed ADHD, but suggest that detectable genetic overlaps may depend ondevelopmental stage.Co-Authors* Presenting AuthorFirst Name Last Name Affiliation E-mailBeate * St Pourcain * MRC IntegrativeEpidemiology Unit (MRCIEU), University of Bristol,UK;  School of Social andCommunity Medicine,University of Bristol, UK;Max Planck Institute forPsycholinguistics, TheNetherlandsbeate.stpourcain@bristol.ac.ukJoanna Martin Stanley Center forPsychiatric Research,Broad Institute of MIT andHarvard, US; Analytic &Translational GeneticsUnit, MassachusettsGeneral Hospital, US; MRCCentre forNeuropsychiatric Geneticsand Genomics, CardiffUniversity, UKmartinjm1@cardiff.ac.ukEvie Stergiakouli MRC IntegrativeEpidemiology Unit (MRCIEU), University of Bristol,UK; School of Social andCommunity Medicine,University of Bristol, UKe.stergiakouli@bristol.ac.uk22015 World Congress of Psychiatric GeneticsElise Robinson Stanley Center forPsychiatric Research,Broad Institute of MIT andHarvard, US; Analytic &Translational GeneticsUnit, MassachusettsGeneral Hospital, USerobinson@atgu.mgh.harvard.eduDavid Skuse Institute of Child Health,University CollegeLondon, UKdskuse@ich.ucl.ac.ukRing Susan MRC IntegrativeEpidemiology Unit (MRCIEU), University of Bristol,UK; School of Social andCommunity Medicine,University of Bristol, UKS.M.Ring@bristol.ac.ukAngelica Ronald Department ofPsychological Sciences,Birkbeck, University ofLondon, UKa.ronald@bbk.ac.ukDavid Evans MRC IntegrativeEpidemiology Unit (MRCIEU), University of Bristol,UK; University ofQueensland DiamantinaInstitute, TranslationalResearch Institute,University of Queensland,Australiad.evans1@uq.edu.auNicholas Timpson MRC IntegrativeEpidemiology Unit (MRCIEU), University of Bristol,UK; School of Social andCommunity Medicine,University of Bristol, UKn.j.timpson@bristol.ac.uk32015 World Congress of Psychiatric GeneticsAnita Thapar MRC Centre forNeuropsychiatric Geneticsand Genomics, CardiffUniversity, UKthapar@cf.ac.ukGeorge Davey Smith MRC IntegrativeEpidemiology Unit (MRCIEU), University of Bristol,UK; School of Social andCommunity Medicine,University of 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 (MC_UU_12013/1-9) and the MRC Centre for Neuropsychiatric Genetics and Genomics issupported by the Medical Research Council, the Wellcome Trust and Cardiff University(079711/Z/06/Z). The UK Medical Research Council and the Wellcome Trust (102215/2/13/2) andthe University of Bristol provide core support for ALSPAC.Human or Animal Ethics Board Review YesSignature Beate St Pourcain4

Genetic links between social-communication traits, ADHD traits and clinical ADHD during development

http://hdl.handle.net/11858/00-001M-0000-0029-57A0-9

Genetic links between social-communication traits, ADHD traits and clinical ADHD during development

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