TY - JOUR
T1 - Identification of common genetic risk variants for autism spectrum disorder
AU - Grove, Jakob
AU - Ripke, Stephan
AU - Als, Thomas D.
AU - Mattheisen, Manuel
AU - Walters, Raymond K.
AU - Won, Hyejung
AU - Pallesen, Jonatan
AU - Agerbo, Esben
AU - Andreassen, Ole A.
AU - Anney, Richard
AU - Awashti, Swapnil
AU - Belliveau, Rich
AU - Bettella, Francesco
AU - Buxbaum, Joseph D.
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Marie
AU - Cerrato, Felecia
AU - Chambert, Kimberly
AU - Christensen, Jane H.
AU - Churchhouse, Claire
AU - Dellenvall, Karin
AU - Demontis, Ditte
AU - De Rubeis, Silvia
AU - Devlin, Bernie
AU - Djurovic, Srdjan
AU - Dumont, Ashley L.
AU - Goldstein, Jacqueline I.
AU - Hansen, Christine S.
AU - Hauberg, Mads Engel
AU - Hollegaard, Mads V.
AU - Hope, Sigrun
AU - Howrigan, Daniel P.
AU - Huang, Hailiang
AU - Hultman, Christina M.
AU - Klei, Lambertus
AU - Maller, Julian
AU - Martin, Joanna
AU - Pedersen, Carsten Bøcker
AU - Davey Smith, George
AU - Pourcain, Beate St
AU - Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium
AU - BUPGEN
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - the 23 and Me Research Team
AU - Adams, Mark J.
AU - Dunn, Erin C
AU - Knowles, James A.
AU - Medland, Sarah E
AU - Owen, Michael J.
AU - Smith, Daniel J.
AU - Tansey, Katherine E.
AU - Yang, Jian
AU - Lewis, Glyn
AU - Madden, Pamela A.F.
PY - 2019/3
Y1 - 2019/3
N2 - Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
AB - Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
UR - http://www.scopus.com/inward/record.url?scp=85062110842&partnerID=8YFLogxK
U2 - 10.1038/s41588-019-0344-8
DO - 10.1038/s41588-019-0344-8
M3 - Article (Academic Journal)
C2 - 30804558
AN - SCOPUS:85062110842
SN - 1061-4036
VL - 51
SP - 431
EP - 444
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -
