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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.accessioned2022-01-07T13:12:33Z
dc.date.available2022-01-07T13:12:33Z
dc.date.issued2021-11-11
dc.identifier.issn2041-1723
dc.identifier.otherPMC8586371
dc.identifier.other34764245
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332302
dc.description.abstractAutism 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.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.subjectHumans
dc.subjectGenetic Predisposition to Disease
dc.subjectRegression Analysis
dc.subjectAttention Deficit Disorder with Hyperactivity
dc.subjectPolymorphism, Single Nucleotide
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectAutism Spectrum Disorder
dc.titleDiscordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy.
dc.typeArticle
dc.date.updated2022-01-07T13:12:32Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
dc.identifier.doi10.17863/CAM.79749
dcterms.dateAccepted2021-10-08
rioxxterms.versionofrecord10.1038/s41467-021-26755-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://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-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (CH/12/2/29428)
pubs.funder-project-idBritish Heart Foundation (RG/18/13/33946)
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)
cam.issuedOnline2021-11-11


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International