Identification of common genetic risk variants for autism spectrum disorder

作者：J. Grove, S. Ripke, T. Als, M. Mattheisen, R. Walters, H. Won, Jonatan Pallesen, E. Agerbo, O. Andreassen, R. Anney, Swapnil Awashti, R. Belliveau, F. Bettella, J. Buxbaum, J. Bybjerg-Grauholm, Marie Bækvad-Hansen, Felecia Cerrato, K. Chambert, J. Christensen, C. Churchhouse, Karin Dellenvall, D. Demontis, S. Rubeis, B. Devlin, S. Djurovic, Ashley L. Dumont, J. Goldstein, C. Hansen, M. Hauberg, M. Hollegaard, S. Hope, D. Howrigan, Hailiang Huang, C. Hultman, L. Klei, J. Maller, Joanna Martin, Alicia R. Martin, J. Moran, M. Nyegaard, T. Nærland, D. Palmer, A. Palotie, C. Pedersen, M. Pedersen, Timothy dPoterba, J. Poulsen, B. S. Pourcain, P. Qvist, K. Rehnström, A. Reichenberg, J. Reichert, E. Robinson, K. Roeder, P. Roussos, E. Saemundsen, S. Sandin, F. Satterstrom, G. D. Smith, H. Stefánsson, S. Steinberg, C. Stevens, P. Sullivan, P. Turley, G. Walters, Xinyi Xu, N. Wray, M. Trzaskowski, E. Byrne, A. Abdellaoui, M. Adams, Tracy M. Air, Till F. M. Andlauer, S. Bacanu, A. Beekman, T. Bigdeli, E. Binder, D. Blackwood, J. Bryois, H. Buttenschøn, N. Cai, E. Castelao, Toni‐Kim Clarke, J. Coleman, L. Colodro-Conde, B. Couvy-Duchesne, N. Craddock, Gregory E. Crawford, G. Davies, I. Deary, F. Degenhardt, E. Derks, N. Direk, C. Dolan, E. Dunn, T. Eley, V. Escott-Price, Farnush Farhadi Hassan Kiadeh, H. Finucane, A. Forstner, J. Frank, Héléna A. Gaspar, M. Gill, F. Goes, S. Gordon, L. Hall, T. Hansen, S. Herms, I. Hickie, P. Hoffmann, G. Homuth, Carsten Horn, J. Hottenga, M. Ising, R. Jansen, E. Jorgenson, J. Knowles, I. Kohane, J. Kraft, Warren W. Kretzschmar, J. Krogh, Z. Kutalik, Yihan Li, P. Lind, D. Macintyre, D. MacKinnon, Robert M. Maier, Wolfgang Maier, J. Marchini, H. Mbarek, Patrick J. McGrath, P. McGuffin, S. Medland, D. Mehta, C. Middeldorp, E. Mihailov, Y. Milaneschi, L. Milani, Francis M. Mondimore, G. Montgomery, S. Mostafavi, N. Mullins, M. Nauck, B. Ng, M. Nivard, D. Nyholt, P. O’Reilly, H. Oskarsson, M. Owen, J. Painter, Roseann E. Peterson, E. Pettersson, W. Peyrot, G. Pistis, D. Posthuma, J. Quiroz, John P. Rice, B. Riley, M. Rivera, S. Mirza, R. Schoevers, E. Schulte, Ling Shen, Jianxin Shi, S. Shyn, E. Sigurdsson, Grant C. B. Sinnamon, J. Smit, Daniel J. Smith, F. Streit, J. Strohmaier, K. Tansey, H. Teismann, A. Teumer, Wesley Thompson, P. Thomson, T. Thorgeirsson, M. Traylor, J. Treutlein, V. Trubetskoy, A. Uitterlinden, D. Umbricht, S. Auwera, A. M. Hemert, A. Viktorin, P. Visscher, Yunpeng Wang, B. Webb, S.M. Weinsheimer, J. Wellmann, G. Willemsen, S. Witt, Yang Wu, H. Xi, Jian Yang, Futao Zhang, V. Arolt, B. Baune, K. Berger, D. Boomsma, S. Cichon, U. Dannlowski, E. D. Geus, J. DePaulo, E. Domenici, K. Domschke, T. Esko, H. Grabe, S. Hamilton, C. Hayward, A. Heath, K. Kendler, S. Kloiber, G. Lewis, Qingqin S. Li, S. Lucae, P. Madden, P. Magnusson, N. G. Martin, A. McIntosh, A. Metspalu, B. Müller-Myhsok, M. Nöthen, M. O’Donovan, S. Paciga, N. Pedersen, B. Penninx, R. Perlis, D. Porteous, J. Potash, M. Preisig, M. Rietschel, C. Schaefer, T. Schulze, J. Smoller, H. Tiemeier, R. Uher, H. Völzke, Myrna M. Weissman, C. Lewis, D. Levinson, G. Breen, M. Agee, B. Alipanahi, A. Auton, R. Bell, K. Bryc, S. Elson, P. Fontanillas, N. Furlotte, Bethann S. Hromatka, K. Huber, A. Kleinman, N. Litterman, M. McIntyre, J. Mountain, E. Noblin, C. Northover, S. Pitts, J. Sathirapongsasuti, O. V. Sazonova, J. Shelton, S. Shringarpure, J. Tung, V. Vacic, C. H. Wilson, K. Stefánsson, D. Geschwind, M. Nordentoft, D. Hougaard, T. Werge, O. Mors, P. Mortensen, B. Neale, M. Daly, A. Børglum · 发表于：Nature Genetics · 年份：2019 · DOI：10.1038/s41588-019-0344-8 · 被引用次数：2071 · 研究领域：Medicine、Biology

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. A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.