Identification of common genetic risk variants for autism spectrum disorder

Grove, J. et al. (2019) Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 51(3), pp. 431-444. (doi: 10.1038/s41588-019-0344-8) (PMID:30804558) (PMCID:PMC6454898)

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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.

Item Type:Articles
Additional Information:Professor Daniel J. Smith is a member of the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel
Authors: Grove, J., Ripke, S., Als, T. D., Mattheisen, M., Walters, R. K., Won, H., Pallesen, J., Agerbo, E., Andreassen, O. A., Anney, R., Awashti, S., Belliveau, R., Bettella, F., Buxbaum, J. D., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Cerrato, F., Chambert, K., Christensen, J. H., Churchhouse, C., Dellenvall, K., Demontis, D., De Rubeis, S., Devlin, B., Djurovic, S., Dumont, A. L., Goldstein, J. I., Hansen, C. S., Hauberg, M. E., Hollegaard, M. V., Hope, S., Howrigan, D. P., Huang, H., Hultman, C. M., Klei, L., Maller, J., Martin, J., Martin, A. R., Moran, J. L., Nyegaard, M., Nærland, T., Palmer, D. S., Palotie, A., Pedersen, C. B., Pedersen, M. G., dPoterba, T., Poulsen, J. B., Pourcain, B. S., Qvist, P., Rehnström, K., Reichenberg, A., Reichert, J., Robinson, E. B., Roeder, K., Roussos, P., Saemundsen, E., Sandin, S., Satterstrom, F. K., Davey Smith, G., Stefansson, H., Steinberg, S., Stevens, C. R., Sullivan, P. F., Turley, P., Walters, G. B., Xu, X., Stefansson, K., Geschwind, D. H., Nordentoft, M., Hougaard, D. M., Werge, T., Mors, O., Mortensen, P. B., Neale, B. M., Daly, M. J., Børglum, A. D., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Nature Genetics
Publisher:Nature Research
ISSN (Online):1546-1718
Published Online:25 February 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Genetics 51(3): 431-444
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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