1. Genomic architecture of autism from comprehensive whole-genome sequence annotation.
- Author
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Trost, Brett, Thiruvahindrapuram, Bhooma, Chan, Ada, Engchuan, Worrawat, Higginbotham, Edward, Howe, Jennifer, Loureiro, Livia, Reuter, Miriam, Roshandel, Delnaz, Whitney, Joe, Zarrei, Mehdi, Bookman, Matthew, Somerville, Cherith, Shaath, Rulan, Abdi, Mona, Aliyev, Elbay, Patel, Rohan, Nalpathamkalam, Thomas, Pellecchia, Giovanna, Hamdan, Omar, Kaur, Gaganjot, Wang, Zhuozhi, MacDonald, Jeffrey, Wei, John, Sung, Wilson, Lamoureux, Sylvia, Hoang, Ny, Selvanayagam, Thanuja, Deflaux, Nicole, Geng, Melissa, Ghaffari, Siavash, Bates, John, Young, Edwin, Ding, Qiliang, Shum, Carole, DAbate, Lia, Bradley, Clarrisa, Rutherford, Annabel, Aguda, Vernie, Apresto, Beverly, Chen, Nan, Desai, Sachin, Du, Xiaoyan, Fong, Matthew, Pullenayegum, Sanjeev, Samler, Kozue, Wang, Ting, Ho, Karen, Paton, Tara, Pereira, Sergio, Herbrick, Jo-Anne, Wintle, Richard, Fuerth, Jonathan, Noppornpitak, Juti, Ward, Heather, Magee, Patrick, Al Baz, Ayman, Kajendirarajah, Usanthan, Kapadia, Sharvari, Vlasblom, Jim, Valluri, Monica, Green, Joseph, Seifer, Vicki, Quirbach, Morgan, Rennie, Olivia, Kelley, Elizabeth, Masjedi, Nina, Lord, Catherine, Szego, Michael, Zawati, Man, Lang, Michael, Strug, Lisa, Marshall, Christian, Costain, Gregory, Calli, Kristina, Iaboni, Alana, Yusuf, Afiqah, Ambrozewicz, Patricia, Gallagher, Louise, Amaral, David, Brian, Jessica, Elsabbagh, Mayada, Georgiades, Stelios, Messinger, Daniel, Ozonoff, Sally, Sebat, Jonathan, Sjaarda, Calvin, Smith, Isabel, Szatmari, Peter, Zwaigenbaum, Lonnie, Kushki, Azadeh, Frazier, Thomas, Vorstman, Jacob, Fakhro, Khalid, Fernandez, Bridget, Lewis, M, Weksberg, Rosanna, Fiume, Marc, Yuen, Ryan, and Anagnostou, Evdokia
- Subjects
autism spectrum disorder ,copy-number variation ,neurodevelopmental disorders ,phenotype measures ,polygenic risk scores ,rare variants ,structural variation ,whole-genome sequencing ,Humans ,Autism Spectrum Disorder ,Autistic Disorder ,Genetic Predisposition to Disease ,DNA Copy Number Variations ,Genomics - Abstract
Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.
- Published
- 2022