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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.
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; Bækvad-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 I.; Hansen, Christine S.; Hauberg, Mads Engel; Hollegaard, Mads V.; Hope, Sigrun; Howrigan, Daniel P.; Huang, Hailiang; Hultman, Christina M.; Klei, Lambertus; Maller, Julian; Martin, Joanna; Martin, Alicia R.; Moran, Jennifer L.; Nyegaard, Mette; Nærland, Terje; Palmer, Duncan S.; Palotie, Aarno; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Dpoterba, Timothy; Poulsen, Jesper Buchhave; Pourcain, Beate St; Qvist, Per; Rehnström, Karola; Reichenberg, Abraham; Reichert, Jennifer; Robinson, Elise B.; Roeder, Kathryn; Roussos, Panos; Saemundsen, Evald; Sandin, Sven; Satterstrom, F. Kyle; Davey Smith, George; Stefansson, Hreinn; Steinberg, Stacy; Stevens, Christine R.; Sullivan, Patrick F.; Turley, Patrick; Walters, G. Bragi; Xu, Xinyi; 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; Buttenschøn, Henriette N.; Cai, Na; Castelao, Enrique; Clarke, Toni-Kim; Coleman, Jonathan R. I.; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E.; Davies, Gail; Deary, Ian J.; Degenhardt, Franziska; Derks, Eske M.; Direk, Nese; Dolan, Conor V.; Dunn, Erin C.; Eley, Thalia C.; Escott-Price, Valentina; Kiadeh, Farnush Farhadi Hassan; Finucane, Hilary K.; Forstner, Andreas J.; Frank, Josef; Gaspar, Héléna 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, Zoltán; 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 I.; 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, André 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, Jürgen; Willemsen, Gonneke; Witt, Stephanie H.; Wu, Yang; Xi, Hualin S.; Yang, Jian; Zhang, Futao; Arolt, Volker; Baune, Bernhard T.; Berger, Klaus; Boomsma, Dorret I.; Cichon, Sven; Dannlowski, Udo; de Geus, E. J. C.; Depaulo, J. Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; 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; Müller-Myhsok, Bertram; Nöthen, 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; Völzke, 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 V.; Shelton, Janie F.; Shringarpure, Suyash; Tung, Joyce Y.; Vacic, Vladimir; Wilson, Catherine H.; Stefansson, Kari; Geschwind, Daniel H.; Nordentoft, Merete; Hougaard, David M.; Werge, Thomas; Mors, Ole; Mortensen, Preben Bo; Neale, Benjamin M.; Daly, Mark J.; Børglum, Anders D.. - In: NATURE GENETICS. - ISSN 1061-4036. - 2019, 51:3(2019), pp. 431-444. [10.1038/s41588-019-0344-8]
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;Bækvad-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 I.;Hansen, Christine S.;Hauberg, Mads Engel;Hollegaard, Mads V.;Hope, Sigrun;Howrigan, Daniel P.;Huang, Hailiang;Hultman, Christina M.;Klei, Lambertus;Maller, Julian;Martin, Joanna;Martin, Alicia R.;Moran, Jennifer L.;Nyegaard, Mette;Nærland, Terje;Palmer, Duncan S.;Palotie, Aarno;Pedersen, Carsten Bøcker;Pedersen, Marianne Giørtz;dPoterba, Timothy;Poulsen, Jesper Buchhave;Pourcain, Beate St;Qvist, Per;Rehnström, Karola;Reichenberg, Abraham;Reichert, Jennifer;Robinson, Elise B.;Roeder, Kathryn;Roussos, Panos;Saemundsen, Evald;Sandin, Sven;Satterstrom, F. Kyle;Davey Smith, George;Stefansson, Hreinn;Steinberg, Stacy;Stevens, Christine R.;Sullivan, Patrick F.;Turley, Patrick;Walters, G. Bragi;Xu, Xinyi;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;Buttenschøn, Henriette N.;Cai, Na;Castelao, Enrique;Clarke, Toni-Kim;Coleman, Jonathan R. I.;Colodro-Conde, Lucía;Couvy-Duchesne, Baptiste;Craddock, Nick;Crawford, Gregory E.;Davies, Gail;Deary, Ian J.;Degenhardt, Franziska;Derks, Eske M.;Direk, Nese;Dolan, Conor V.;Dunn, Erin C.;Eley, Thalia C.;Escott-Price, Valentina;Kiadeh, Farnush Farhadi Hassan;Finucane, Hilary K.;Forstner, Andreas J.;Frank, Josef;Gaspar, Héléna 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, Zoltán;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 I.;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, André 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, Jürgen;Willemsen, Gonneke;Witt, Stephanie H.;Wu, Yang;Xi, Hualin S.;Yang, Jian;Zhang, Futao;Arolt, Volker;Baune, Bernhard T.;Berger, Klaus;Boomsma, Dorret I.;Cichon, Sven;Dannlowski, Udo;de Geus, E. J. C.;DePaulo, J. Raymond;Domenici, Enrico;Domschke, Katharina;Esko, Tõnu;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;Müller-Myhsok, Bertram;Nöthen, 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;Völzke, 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 V.;Shelton, Janie F.;Shringarpure, Suyash;Tung, Joyce Y.;Vacic, Vladimir;Wilson, Catherine H.;Stefansson, Kari;Geschwind, Daniel H.;Nordentoft, Merete;Hougaard, David M.;Werge, Thomas;Mors, Ole;Mortensen, Preben Bo;Neale, Benjamin M.;Daly, Mark J.;Børglum, Anders D.
2019-01-01
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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/230473
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
