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Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

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dc.contributor.authorDemontis, Ditte
dc.contributor.authorWalters, Raymond K.
dc.contributor.authorRajagopal, Veera M.
dc.contributor.authorWaldman, Irwin D.
dc.contributor.authorGrove, Jakob
dc.contributor.authorAls, Thomas D.
dc.contributor.authorDalsgaard, Søren
dc.contributor.authorRibasas, Marta
dc.contributor.authorBybjerg-Grauholm, Jonas
dc.contributor.authorBækvad-Hansen, Maria
dc.contributor.authorWerge, Thomas
dc.contributor.authorNordentoft, Merete
dc.contributor.authorMors, Ole
dc.contributor.authorMortensen, Preben Bo
dc.contributor.author(PGC), ADHD Working Group of the Psychiatric Genomics Consortium
dc.contributor.authorAndreassen, Ole A.
dc.contributor.authorArranz, Maria Jesús
dc.contributor.authorBanaschewski, Tobias
dc.contributor.authorBau, Claiton
dc.contributor.authorBellgrove, Mark
dc.contributor.authorBiederman, Joseph
dc.contributor.authorBrikell, Isabell
dc.contributor.authorBuitelaar, Jan K.
dc.contributor.authorBurton, Christie L.
dc.contributor.authorCasas, Miguel
dc.contributor.authorCrosbie, Jennifer
dc.contributor.authorDoyle, Alysa E.
dc.contributor.authorEbstein, Richard P.
dc.contributor.authorElia, Josephine
dc.contributor.authorElizabeth, Corfield C.
dc.contributor.authorGrevet, Eugenio
dc.contributor.authorGrizenko, Natalie
dc.contributor.authorHavdahl, Alexandra
dc.contributor.authorHawi, Ziarih
dc.contributor.authorHebebrand, Johannes
dc.contributor.authorHervas, Amaia
dc.contributor.authorHohmann, Sarah
dc.contributor.authorHaavik, Jan
dc.contributor.authorJoober, Ridha
dc.contributor.authorKent, Lindsey
dc.contributor.authorKuntsi, Jonna
dc.contributor.authorLangley, Kate
dc.contributor.authorLarsson, Henrik
dc.contributor.authorLesch, Klaus-Peter
dc.contributor.authorLeung, Patrick W. L.
dc.contributor.authorLiao, Calwing
dc.contributor.authorLoo, Sandra K.
dc.contributor.authorMartin, Joanna
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorMedland, Sarah E.
dc.contributor.authorMiranda, Ana
dc.contributor.authorMota, Nina Roth
dc.contributor.authorOades, Robert D.
dc.contributor.authorRamos-Quiroga, Josep Antoni
dc.contributor.authorReif, Andreas
dc.contributor.authorRietschel, Marcella
dc.contributor.authorRoeyers, Herbert
dc.contributor.authorRohde, Luis Augusto
dc.contributor.authorRothenberger, Aribert
dc.contributor.authorRovira, Paula
dc.contributor.authorSánchez-Mora, Cristina
dc.contributor.authorSchachar, Russell James
dc.contributor.authorSengupta, Sarojini
dc.contributor.authorArtigas, Maria Soler
dc.contributor.authorSteinhausen, Hans-Christoph
dc.contributor.authorThapar, Anita
dc.contributor.authorWitt, Stephanie H.
dc.contributor.authorYang, Li
dc.contributor.authorZayats, Tetyana
dc.contributor.authorZhang-James, Yanli
dc.contributor.authorCormand, Bru
dc.contributor.authorHougaard, David M.
dc.contributor.authorNeale, Benjamin M.
dc.contributor.authorFranke, Barbara
dc.contributor.authorFaraone, Stephen V.
dc.contributor.authorBørglum, Anders D.
dc.date.accessioned2021-02-04T11:30:11Z
dc.date.available2021-02-04T11:30:11Z
dc.date.issued2021-01-25
dc.identifier272706531
dc.identifierfb87a9c1-ecfa-443e-a448-3bd3a5475461
dc.identifier85099802296
dc.identifier.citationDemontis , D , Walters , R K , Rajagopal , V M , Waldman , I D , Grove , J , Als , T D , Dalsgaard , S , Ribasas , M , Bybjerg-Grauholm , J , Bækvad-Hansen , M , Werge , T , Nordentoft , M , Mors , O , Mortensen , P B , (PGC) , ADHD W G O T P G C , Andreassen , O A , Arranz , M J , Banaschewski , T , Bau , C , Bellgrove , M , Biederman , J , Brikell , I , Buitelaar , J K , Burton , C L , Casas , M , Crosbie , J , Doyle , A E , Ebstein , R P , Elia , J , Elizabeth , C C , Grevet , E , Grizenko , N , Havdahl , A , Hawi , Z , Hebebrand , J , Hervas , A , Hohmann , S , Haavik , J , Joober , R , Kent , L , Kuntsi , J , Langley , K , Larsson , H , Lesch , K-P , Leung , P W L , Liao , C , Loo , S K , Martin , J , Martin , N G , Medland , S E , Miranda , A , Mota , N R , Oades , R D , Ramos-Quiroga , J A , Reif , A , Rietschel , M , Roeyers , H , Rohde , L A , Rothenberger , A , Rovira , P , Sánchez-Mora , C , Schachar , R J , Sengupta , S , Artigas , M S , Steinhausen , H-C , Thapar , A , Witt , S H , Yang , L , Zayats , T , Zhang-James , Y , Cormand , B , Hougaard , D M , Neale , B M , Franke , B , Faraone , S V & Børglum , A D 2021 , ' Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder ' , Nature Communications , vol. 12 , no. 1 , 576 . https://doi.org/10.1038/s41467-020-20443-2en
dc.identifier.issn2041-1723
dc.identifier.otherRIS: urn:19D1C98E5BBBA632BDCF861FEAAF769F
dc.identifier.otherRIS: Demontis2021
dc.identifier.otherORCID: /0000-0002-5315-3399/work/88267105
dc.identifier.urihttps://hdl.handle.net/10023/21375
dc.description.abstractAttention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.
dc.format.extent12
dc.format.extent1067954
dc.language.isoeng
dc.relation.ispartofNature Communicationsen
dc.subjectADHDen
dc.subjectGenome-wide association studiesen
dc.subjectQH426 Geneticsen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectDASen
dc.subject.lccQH426en
dc.subject.lccRC0321en
dc.titleRisk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorderen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.identifier.doi10.1038/s41467-020-20443-2
dc.description.statusPeer revieweden
dc.identifier.urlhttps://www.nature.com/articles/s41467-021-21566-wen


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