000877954 001__ 877954
000877954 005__ 20210130005313.0
000877954 0247_ $$2doi$$a10.1038/s41398-020-00906-2
000877954 0247_ $$2pmid$$apmid:32624584
000877954 0247_ $$2pmc$$apmc:PMC7335742
000877954 0247_ $$2Handle$$a2128/25273
000877954 0247_ $$2altmetric$$aaltmetric:85307209
000877954 0247_ $$2WOS$$aWOS:000549816200002
000877954 037__ $$aFZJ-2020-02533
000877954 041__ $$aeng
000877954 082__ $$a610
000877954 1001_ $$00000-0002-8026-7332$$aYousaf, Afsheen$$b0$$eCorresponding author
000877954 245__ $$aQuantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder.
000877954 260__ $$aLondon$$bNature Publishing Group$$c2020
000877954 3367_ $$2DRIVER$$aarticle
000877954 3367_ $$2DataCite$$aOutput Types/Journal article
000877954 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1594733303_25174
000877954 3367_ $$2BibTeX$$aARTICLE
000877954 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000877954 3367_ $$00$$2EndNote$$aJournal Article
000877954 520__ $$aAutism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h2SNP = 0.2-0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3-3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits-partially replicating previous findings-and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains.
000877954 536__ $$0G:(DE-HGF)POF3-571$$a571 - Connectivity and Activity (POF3-571)$$cPOF3-571$$fPOF III$$x0
000877954 536__ $$0G:(EU-Grant)945539$$aHBP SGA3 - Human Brain Project Specific Grant Agreement 3 (945539)$$c945539$$x1
000877954 536__ $$0G:(EU-Grant)785907$$aHBP SGA2 - Human Brain Project Specific Grant Agreement 2 (785907)$$c785907$$fH2020-SGA-FETFLAG-HBP-2017$$x2
000877954 588__ $$aDataset connected to CrossRef, PubMed,
000877954 7001_ $$0P:(DE-HGF)0$$aWaltes, Regina$$b1
000877954 7001_ $$0P:(DE-HGF)0$$aHaslinger, Denise$$b2
000877954 7001_ $$0P:(DE-HGF)0$$aKlauck, Sabine M$$b3
000877954 7001_ $$0P:(DE-HGF)0$$aDuketis, Eftichia$$b4
000877954 7001_ $$aSachse, Michael$$b5
000877954 7001_ $$0P:(DE-HGF)0$$aVoran, Anette$$b6
000877954 7001_ $$0P:(DE-HGF)0$$aBiscaldi, Monica$$b7
000877954 7001_ $$0P:(DE-Juel1)131741$$aSchulte-Rüther, Martin$$b8$$eCorresponding author
000877954 7001_ $$0P:(DE-Juel1)140234$$aCichon, Sven$$b9
000877954 7001_ $$aNöthen, Markus$$b10
000877954 7001_ $$0P:(DE-HGF)0$$aAckermann, Jörg$$b11
000877954 7001_ $$0P:(DE-HGF)0$$aKoch, Ina$$b12
000877954 7001_ $$0P:(DE-HGF)0$$aFreitag, Christine M$$b13
000877954 7001_ $$0P:(DE-HGF)0$$aChiocchetti, Andreas G$$b14
000877954 773__ $$0PERI:(DE-600)2609311-X$$a10.1038/s41398-020-00906-2$$gVol. 10, no. 1, p. 215$$n1$$p215$$tTranslational Psychiatry$$v10$$x2158-3188$$y2020
000877954 8564_ $$uhttps://juser.fz-juelich.de/record/877954/files/Yousaf%20etal_Transl%20Psych_2020.pdf$$yOpenAccess
000877954 8564_ $$uhttps://juser.fz-juelich.de/record/877954/files/Yousaf%20etal_Transl%20Psych_2020.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000877954 909CO $$ooai:juser.fz-juelich.de:877954$$pdnbdelivery$$pec_fundedresources$$pVDB$$pdriver$$popen_access$$popenaire
000877954 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131741$$aForschungszentrum Jülich$$b8$$kFZJ
000877954 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)140234$$aForschungszentrum Jülich$$b9$$kFZJ
000877954 9131_ $$0G:(DE-HGF)POF3-571$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vConnectivity and Activity$$x0
000877954 9141_ $$y2020
000877954 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-01-16
000877954 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000877954 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bTRANSL PSYCHIAT : 2018$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000877954 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$f2020-01-16
000877954 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bTRANSL PSYCHIAT : 2018$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2020-01-16
000877954 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2020-01-16
000877954 9201_ $$0I:(DE-Juel1)INM-1-20090406$$kINM-1$$lStrukturelle und funktionelle Organisation des Gehirns$$x0
000877954 9201_ $$0I:(DE-Juel1)INM-11-20170113$$kINM-11$$lJara-Institut Quantum Information$$x1
000877954 980__ $$ajournal
000877954 980__ $$aVDB
000877954 980__ $$aUNRESTRICTED
000877954 980__ $$aI:(DE-Juel1)INM-1-20090406
000877954 980__ $$aI:(DE-Juel1)INM-11-20170113
000877954 9801_ $$aFullTexts