Author:
Grove Jakob,Ripke Stephan,Als Thomas D.,Mattheisen Manuel,Walters Raymond,Won Hyejung,Pallesen Jonatan,Agerbo Esben,Andreassen Ole A.,Anney Richard,Belliveau Rich,Bettella Francesco,Buxbaum Joseph D.,Bybjerg-Grauholm Jonas,Bækved-Hansen Marie,Cerrato Felecia,Chambert Kimberly,Christensen Jane H.,Churchhouse Claire,Dellenvall Karin,Demontis Ditte,De Rubeis Silvia,Devlin Bernie,Djurovic Srdjan,Dumont Ashle,Goldstein Jacqueline,Hansen Christine S.,Hauberg Mads Engel,Hollegaard Mads V.,Hope Sigrun,Howrigan Daniel P.,Huang Hailiang,Hultman Christina,Klei Lambertus,Maller Julian,Martin Joanna,Martin Alicia R.,Moran Jennifer,Nyegaard Mette,Nærland Terje,Palmer Duncan S.,Palotie Aarno,Pedersen Carsten B.,Pedersen Marianne G.,Poterba Timothy,Poulsen Jesper B.,St Pourcain Beate,Qvist Per,Rehnström Karola,Reichenberg Avi,Reichert Jennifer,Robinson Elise B.,Roeder Kathryn,Roussos Panos,Saemundsen Evald,Sandin Sven,Satterstrom F. Kyle,Smith George D.,Stefansson Hreinn,Stefansson Kari,Steinberg Stacy,Stevens Christine,Sullivan Patrick F.,Turley Patrick,Walters G. Bragi,Xu Xinyi,Geschwind Daniel,Nordentoft Merete,Hougaard David M.,Werge Thomas,Mors Ole,Mortensen Preben Bo,Neale Benjamin M.,Daly Mark J.,Børglum Anders D.,
Abstract
AbstractAutism 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 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes, in contrast to what is typically seen in other complex disorders. 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, just as it has been in a broad range of important psychiatric and diverse medical phenotypes.
Publisher
Cold Spring Harbor Laboratory