Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

Stephan J. Sanders, A. Gulhan Ercan-Sencicek, Vanessa Hus, Rui Luo, Michael T. Murtha, Daniel Moreno-De-Luca, Su H. Chu, Michael P. Moreau, Abha R. Gupta, Susanne A. Thomson, Christopher E. Mason, Kaya Bilguvar, Patricia B.S. Celestino-Soper, Murim Choi, Emily L. Crawford, Lea Davis, Nicole R. Davis Wright, Rahul M. Dhodapkar, Michael DiCola, Nicholas M. DiLulloThomas V. Fernandez, Vikram Fielding-Singh, Daniel O. Fishman, Stephanie Frahm, Rouben Garagaloyan, Gerald S. Goh, Sindhuja Kammela, Lambertus Klei, Jennifer K. Lowe, Sabata C. Lund, Anna D. McGrew, Kyle A. Meyer, William J. Moffat, John D. Murdoch, Brian J. O'Roak, Gordon T. Ober, Rebecca S. Pottenger, Melanie J. Raubeson, Youeun Song, Qi Wang, Brian L. Yaspan, Timothy W. Yu, Ilana R. Yurkiewicz, Arthur L. Beaudet, Rita M. Cantor, Martin Curland, Dorothy E. Grice, Murat Günel, Richard P. Lifton, Shrikant M. Mane, Donna M. Martin, Chad A. Shaw, Michael Sheldon, Jay A. Tischfield, Christopher A. Walsh, Eric M. Morrow, David H. Ledbetter, Eric Fombonne, Catherine Lord, Christa Lese Martin, Andrew I. Brooks, James S. Sutcliffe, Edwin H. Cook, Daniel Geschwind, Kathryn Roeder, Bernie Devlin, Matthew W. State

Research output: Contribution to journalArticlepeer-review

970 Scopus citations


We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6-12.0, p = 2.4 × 10-7). We estimate there are 130-234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.

Original languageEnglish (US)
Pages (from-to)863-885
Number of pages23
Issue number5
StatePublished - Jun 9 2011
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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