Identification of common genetic risk variants for autism spectrum disorder

Grove, Jakob, Ripke, Stephan, Als, Thomas D., Mattheisen, Manuel, Walters, Raymond K., Won, Hyejung, Pallesen, Jonatan, Agerbo, Esben, Andreassen, Ole A., Anney, Richard, Awashti, Swapnil, Belliveau, Rich, Bettella, Francesco, Buxbaum, Joseph D., Bybjerg-Grauholm, Jonas, Baekvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Christensen, Jane H., Churchhouse, Claire, Dellenvall, Karin, Demontis, Ditte, De Rubeis, Silvia, Devlin, Bernie, Djurovic, Srdjan, Dumont, Ashley L., Goldstein, Jacqueline, Hansen, Christine S., Hauberg, Mads Engel, Hollegaard, Mads, Hope, Sigrun, Howrigan, Daniel P., Huang, Hailiang, Hultman, Christina M., Klei, Lambertus, Maller, Julian, Martin, Joanna, Martin, Alicia R., Moran, Jennifer L., Nyegaard, Mette, Naerland, Terje, Palmer, Duncan S., Palotie, Aarno, Pedersen, Carsten Bocker, Pedersen, Marianne Giortz, dPoterba, Timothy, Poulsen, Jesper Buchhave, St Pourcain, Beate, Qvist, Per, Rehnstrom, Karola, Reichenberg, Abraham, Reichert, Jennifer, Robinson, Elise B., Roeder, Kathryn, Roussos, Panos, Saemundsen, Evald, Sandin, Sven, Satterstrom, F. Kyle, Smith, George Davey, Stefansson, Hreinn, Steinberg, Stacy, Stevens, Christine R., Sullivan, Patrick F., Turley, Patrick, Walters, G. Bragi, Xu, Xinyi, Stefansson, Kari, Geschwind, Daniel H., Nordentoft, Merete, Hougaard, David M., Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Neale, Benjamin M., Daly, Mark J., Borglum, Anders D., Wray, Naomi R., Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas H. R., Bryois, Julien, Buttenschon, Henriette N., Cai, Na, Castelao, Enrique, Clarke, Toni-Kim, Coleman, Jonathan R., Colodro-Conde, Lucia, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor, Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Forstner, Andreas J., Frank, Josef, Gaspar, Helena A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Hall, Lynsey S., Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltan, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley, Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andr G., Umbricht, Daniel, Van Der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Juergen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret, Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tonu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mueller-Myhsok, Bertram, Noethen, Markus M., O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Tiemeier, Henning, Uher, Rudolf, Voelzke, Henry, Weissman, Myrna M., Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hromatka, Bethann S., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McIntyre, Matthew H., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga, Shelton, Janie F., Shringarpure, Suyash, Tung, Joyce Y., Vacic, Vladimir, and Wilson, Catherine H. (2019) Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 51 (3). pp. 431-444.

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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.

Item ID: 57534
Item Type: Article (Research - C1)
ISSN: 1546-1718
Copyright Information: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2019
Date Deposited: 20 Mar 2019 07:33
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320213 Medical genetics (excl. cancer genetics) @ 50%
42 HEALTH SCIENCES > 4203 Health services and systems > 420313 Mental health services @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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