| Literature DB >> 30804558 |
Jakob Grove1,2,3,4, Stephan Ripke5,6,7, Thomas D Als1,2,3, Manuel Mattheisen1,2,3,8,9, Raymond K Walters5,6, Hyejung Won10,11, Jonatan Pallesen1,2,3, Esben Agerbo1,12,13, Ole A Andreassen14,15, Richard Anney16, Swapnil Awashti7, Rich Belliveau6, Francesco Bettella14,15, Joseph D Buxbaum17,18,19,20, Jonas Bybjerg-Grauholm1,21, Marie Bækvad-Hansen1,21, Felecia Cerrato6, Kimberly Chambert6, Jane H Christensen1,2,3, Claire Churchhouse5,6,22, Karin Dellenvall23, Ditte Demontis1,2,3, Silvia De Rubeis17,18, Bernie Devlin24, Srdjan Djurovic14,25, Ashley L Dumont6, Jacqueline I Goldstein5,6,22, Christine S Hansen1,21,26, Mads Engel Hauberg1,2,3, Mads V Hollegaard1,21, Sigrun Hope14,27, Daniel P Howrigan5,6, Hailiang Huang5,6, Christina M Hultman23, Lambertus Klei24, Julian Maller6,28,29, Joanna Martin6,16,23, Alicia R Martin5,6,22, Jennifer L Moran6, Mette Nyegaard1,2,3, Terje Nærland14,30, Duncan S Palmer5,6, Aarno Palotie5,6,22,31, Carsten Bøcker Pedersen1,12,13, Marianne Giørtz Pedersen1,12,13, Timothy dPoterba5,6,22, Jesper Buchhave Poulsen1,21, Beate St Pourcain32,33,34, Per Qvist1,2,3, Karola Rehnström35, Abraham Reichenberg17,18,19, Jennifer Reichert17,18, Elise B Robinson5,6,36, Kathryn Roeder37,38, Panos Roussos18,39,40,41, Evald Saemundsen42, Sven Sandin17,18,23, F Kyle Satterstrom5,6,22, George Davey Smith33,43, Hreinn Stefansson44, Stacy Steinberg44, Christine R Stevens6, Patrick F Sullivan10,23,45, Patrick Turley5,6, G Bragi Walters44,46, Xinyi Xu17,18, Kari Stefansson44,46, Daniel H Geschwind47,48,49, Merete Nordentoft1,50, David M Hougaard1,21, Thomas Werge1,26,51, Ole Mors1,52, Preben Bo Mortensen1,2,12,13, Benjamin M Neale5,6,22, Mark J Daly53,54,55,56, Anders D Børglum57,58,59.
Abstract
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.Entities:
Mesh：
Year: 2019 PMID： 30804558 PMCID： PMC6454898 DOI： 10.1038/s41588-019-0344-8
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330