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 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 journalArticle

762 Citations (Scopus)

Abstract

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
JournalNeuron
Volume70
Issue number5
DOIs
StatePublished - Jun 9 2011
Externally publishedYes

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Williams Syndrome
Autistic Disorder
Human Genome
Genes
Personality
Genome
Autism Spectrum Disorder

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., ... State, M. W. (2011). Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism. Neuron, 70(5), 863-885. https://doi.org/10.1016/j.neuron.2011.05.002

Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism. / Sanders, Stephan J.; Ercan-Sencicek, A. Gulhan; Hus, Vanessa; Luo, Rui; Murtha, Michael T.; Moreno-De-Luca, Daniel; Chu, Su H.; Moreau, Michael P.; Gupta, Abha R.; Thomson, Susanne A.; Mason, Christopher E.; Bilguvar, Kaya; Celestino-Soper, Patricia B S; Choi, Murim; Crawford, Emily L.; Davis, Lea; Davis Wright, Nicole R.; Dhodapkar, Rahul M.; DiCola, Michael; DiLullo, Nicholas M.; Fernandez, Thomas V.; Fielding-Singh, Vikram; Fishman, Daniel O.; Frahm, Stephanie; Garagaloyan, Rouben; Goh, Gerald S.; Kammela, Sindhuja; Klei, Lambertus; Lowe, Jennifer K.; Lund, Sabata C.; McGrew, Anna D.; Meyer, Kyle A.; Moffat, William J.; Murdoch, John D.; O'Roak, Brian; Ober, Gordon T.; Pottenger, Rebecca S.; Raubeson, Melanie J.; Song, Youeun; Wang, Qi; Yaspan, Brian L.; Yu, Timothy W.; Yurkiewicz, Ilana R.; Beaudet, Arthur L.; Cantor, Rita M.; Curland, Martin; Grice, Dorothy E.; Günel, Murat; Lifton, Richard P.; Mane, Shrikant M.; Martin, Donna M.; Shaw, Chad A.; Sheldon, Michael; Tischfield, Jay A.; Walsh, Christopher A.; Morrow, Eric M.; Ledbetter, David H.; Fombonne, Eric; Lord, Catherine; Martin, Christa Lese; Brooks, Andrew I.; Sutcliffe, James S.; Cook, Edwin H.; Geschwind, Daniel; Roeder, Kathryn; Devlin, Bernie; State, Matthew W.

In: Neuron, Vol. 70, No. 5, 09.06.2011, p. 863-885.

Research output: Contribution to journalArticle

Sanders, SJ, Ercan-Sencicek, AG, Hus, V, Luo, R, Murtha, MT, Moreno-De-Luca, D, Chu, SH, Moreau, MP, Gupta, AR, Thomson, SA, Mason, CE, Bilguvar, K, Celestino-Soper, PBS, Choi, M, Crawford, EL, Davis, L, Davis Wright, NR, Dhodapkar, RM, DiCola, M, DiLullo, NM, Fernandez, TV, Fielding-Singh, V, Fishman, DO, Frahm, S, Garagaloyan, R, Goh, GS, Kammela, S, Klei, L, Lowe, JK, Lund, SC, McGrew, AD, Meyer, KA, Moffat, WJ, Murdoch, JD, O'Roak, B, Ober, GT, Pottenger, RS, Raubeson, MJ, Song, Y, Wang, Q, Yaspan, BL, Yu, TW, Yurkiewicz, IR, Beaudet, AL, Cantor, RM, Curland, M, Grice, DE, Günel, M, Lifton, RP, Mane, SM, Martin, DM, Shaw, CA, Sheldon, M, Tischfield, JA, Walsh, CA, Morrow, EM, Ledbetter, DH, Fombonne, E, Lord, C, Martin, CL, Brooks, AI, Sutcliffe, JS, Cook, EH, Geschwind, D, Roeder, K, Devlin, B & State, MW 2011, 'Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism', Neuron, vol. 70, no. 5, pp. 863-885. https://doi.org/10.1016/j.neuron.2011.05.002
Sanders, Stephan J. ; Ercan-Sencicek, A. Gulhan ; Hus, Vanessa ; Luo, Rui ; Murtha, Michael T. ; Moreno-De-Luca, Daniel ; Chu, Su H. ; Moreau, Michael P. ; Gupta, Abha R. ; Thomson, Susanne A. ; Mason, Christopher E. ; Bilguvar, Kaya ; Celestino-Soper, Patricia B S ; Choi, Murim ; Crawford, Emily L. ; Davis, Lea ; Davis Wright, Nicole R. ; Dhodapkar, Rahul M. ; DiCola, Michael ; DiLullo, Nicholas M. ; Fernandez, Thomas V. ; Fielding-Singh, Vikram ; Fishman, Daniel O. ; Frahm, Stephanie ; Garagaloyan, Rouben ; Goh, Gerald S. ; Kammela, Sindhuja ; Klei, Lambertus ; Lowe, Jennifer K. ; Lund, Sabata C. ; McGrew, Anna D. ; Meyer, Kyle A. ; Moffat, William J. ; Murdoch, John D. ; O'Roak, Brian ; Ober, Gordon T. ; Pottenger, Rebecca S. ; Raubeson, Melanie J. ; Song, Youeun ; Wang, Qi ; Yaspan, Brian L. ; Yu, Timothy W. ; Yurkiewicz, Ilana R. ; Beaudet, Arthur L. ; Cantor, Rita M. ; Curland, Martin ; Grice, Dorothy E. ; Günel, Murat ; Lifton, Richard P. ; Mane, Shrikant M. ; Martin, Donna M. ; Shaw, Chad A. ; Sheldon, Michael ; Tischfield, Jay A. ; Walsh, Christopher A. ; Morrow, Eric M. ; Ledbetter, David H. ; Fombonne, Eric ; Lord, Catherine ; Martin, Christa Lese ; Brooks, Andrew I. ; Sutcliffe, James S. ; Cook, Edwin H. ; Geschwind, Daniel ; Roeder, Kathryn ; Devlin, Bernie ; State, Matthew W. / Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism. In: Neuron. 2011 ; Vol. 70, No. 5. pp. 863-885.
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T1 - Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

AU - Sanders, Stephan J.

AU - Ercan-Sencicek, A. Gulhan

AU - Hus, Vanessa

AU - Luo, Rui

AU - Murtha, Michael T.

AU - Moreno-De-Luca, Daniel

AU - Chu, Su H.

AU - Moreau, Michael P.

AU - Gupta, Abha R.

AU - Thomson, Susanne A.

AU - Mason, Christopher E.

AU - Bilguvar, Kaya

AU - Celestino-Soper, Patricia B S

AU - Choi, Murim

AU - Crawford, Emily L.

AU - Davis, Lea

AU - Davis Wright, Nicole R.

AU - Dhodapkar, Rahul M.

AU - DiCola, Michael

AU - DiLullo, Nicholas M.

AU - Fernandez, Thomas V.

AU - Fielding-Singh, Vikram

AU - Fishman, Daniel O.

AU - Frahm, Stephanie

AU - Garagaloyan, Rouben

AU - Goh, Gerald S.

AU - Kammela, Sindhuja

AU - Klei, Lambertus

AU - Lowe, Jennifer K.

AU - Lund, Sabata C.

AU - McGrew, Anna D.

AU - Meyer, Kyle A.

AU - Moffat, William J.

AU - Murdoch, John D.

AU - O'Roak, Brian

AU - Ober, Gordon T.

AU - Pottenger, Rebecca S.

AU - Raubeson, Melanie J.

AU - Song, Youeun

AU - Wang, Qi

AU - Yaspan, Brian L.

AU - Yu, Timothy W.

AU - Yurkiewicz, Ilana R.

AU - Beaudet, Arthur L.

AU - Cantor, Rita M.

AU - Curland, Martin

AU - Grice, Dorothy E.

AU - Günel, Murat

AU - Lifton, Richard P.

AU - Mane, Shrikant M.

AU - Martin, Donna M.

AU - Shaw, Chad A.

AU - Sheldon, Michael

AU - Tischfield, Jay A.

AU - Walsh, Christopher A.

AU - Morrow, Eric M.

AU - Ledbetter, David H.

AU - Fombonne, Eric

AU - Lord, Catherine

AU - Martin, Christa Lese

AU - Brooks, Andrew I.

AU - Sutcliffe, James S.

AU - Cook, Edwin H.

AU - Geschwind, Daniel

AU - Roeder, Kathryn

AU - Devlin, Bernie

AU - State, Matthew W.

PY - 2011/6/9

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