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dc.contributor.authorVerhoef, Ellen
dc.contributor.authorGrove, Jakob
dc.contributor.authorShapland, Chin Yang
dc.contributor.authorDemontis, Ditte
dc.contributor.authorBurgess, Stephen
dc.contributor.authorRai, Dheeraj
dc.contributor.authorBørglum, Anders D.
dc.contributor.authorSt Pourcain, Beate
dc.date.accessioned2021-11-12T18:56:47Z
dc.date.available2021-11-12T18:56:47Z
dc.date.issued2021-11-11
dc.date.submitted2019-09-03
dc.identifier.others41467-021-26755-1
dc.identifier.other26755
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330610
dc.description.abstractAbstract: Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610–766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/114
dc.subject/631/208/1515
dc.subject/631/208/366
dc.subject/631/208/457
dc.subject/692/699/476
dc.subjectarticle
dc.titleDiscordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy
dc.typeArticle
dc.date.updated2021-11-12T18:56:45Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume12
dc.identifier.doi10.17863/CAM.78054
dcterms.dateAccepted2021-10-08
rioxxterms.versionofrecord10.1038/s41467-021-26755-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidVerhoef, Ellen [0000-0002-8315-1095]
dc.contributor.orcidGrove, Jakob [0000-0003-2284-5744]
dc.contributor.orcidShapland, Chin Yang [0000-0002-5797-1241]
dc.contributor.orcidDemontis, Ditte [0000-0001-9124-2766]
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.contributor.orcidBørglum, Anders D. [0000-0001-8627-7219]
dc.contributor.orcidSt Pourcain, Beate [0000-0002-4680-3517]
dc.identifier.eissn2041-1723
pubs.funder-project-idSimons Foundation (514787)


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