Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism NEURON Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., Chu, S. H., Moreau, M. P., Gupta, A. R., Thomson, S. A., Mason, C. E., Bilguvar, K., Celestino-Soper, P. B., Choi, M., Crawford, E. L., Davis, L., Wright, N. R., Dhodapkar, R. M., DiCola, M., DiLullo, N. M., Fernandez, T. V., Fielding-Singh, V., Fishman, D. O., Frahm, S., Garagaloyan, R., Goh, G. S., Kammela, S., Klei, L., Lowe, J. K., Lund, S. C., McGrew, A. D., Meyer, K. A., Moffat, W. J., Murdoch, J. D., O'Roak, B. J., Ober, G. T., Pottenger, R. S., Raubeson, M. J., Song, Y., Wang, Q., Yaspan, B. L., Yu, T. W., Yurkiewicz, L. R., Beaudet, A. L., Cantor, R. M., Curland, M., Grice, D. E., Guenel, M., Lifton, R. P., Mane, S. M., Martin, D. M., Shaw, C. A., Sheldon, M., Tischfield, J. A., Walsh, C. A., Morrow, E. M., Ledbetter, D. H., Fombonne, E., Lord, C., Martin, C. L., Brooks, A. I., Sutcliffe, J. S., Cook, E. H., Geschwind, D., Roeder, K., Devlin, B., State, M. W. 2011; 70 (5): 863-885


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.

View details for DOI 10.1016/j.neuron.2011.05.002

View details for Web of Science ID 000291843500008

View details for PubMedID 21658581