Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

Ryan K C Yuen, Daniele Merico, Matt Bookman, Jennifer L Howe, Bhooma Thiruvahindrapuram, Rohan V Patel, Joe Whitney, Nicole Deflaux, Jonathan Bingham, Zhuozhi Wang, Giovanna Pellecchia, Janet A Buchanan, Susan Walker, Christian R Marshall, Mohammed Uddin, Mehdi Zarrei, Eric Deneault, Lia D'Abate, Ada J S Chan, Stephanie Koyanagi, Tara Paton, Sergio L Pereira, Ny Hoang, Worrawat Engchuan, Edward J Higginbotham, Karen Ho, Sylvia Lamoureux, Weili Li, Jeffrey R MacDonald, Thomas Nalpathamkalam, Wilson W L Sung, Fiona J Tsoi, John Wei, Lizhen Xu, Anne-Marie Tasse, Emily Kirby, William Van Etten, Simon Twigger, Wendy Roberts, Irene Drmic, Sanne Jilderda, Bonnie MacKinnon Modi, Barbara Kellam, Michael Szego, Cheryl Cytrynbaum, Rosanna Weksberg, Lonnie Zwaigenbaum, Marc Woodbury-Smith, Jessica Brian, Lili Senman, Alana Iaboni, Krissy Doyle-Thomas, Ann Thompson, Christina Chrysler, Jonathan Leef, Tal Savion-Lemieux, Isabel M Smith, Xudong Liu, Rob Nicolson, Vicki Seifer, Angie Fedele, Edwin H Cook, Stephen Dager, Annette Estes, Louise Gallagher, Beth A Malow, Jeremy R Parr, Sarah J Spence, Jacob Vorstman, Brendan J Frey, James T Robinson, Lisa J Strug, Bridget A Fernandez, Mayada Elsabbagh, Melissa T Carter, Joachim Hallmayer, Bartha M Knoppers, Evdokia Anagnostou, Peter Szatmari, Robert H Ring, David Glazer, Mathew T Pletcher, Stephen W Scherer

We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10(-4)). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.