The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability
作者： Tarjinder Singh , , James T R Walters , Mandy Johnstone , David Curtis
DOI: 10.1038/NG.3903
关键词:
摘要: By performing a meta-analysis of rare coding variants in whole-exome sequences from 4,133 schizophrenia cases and 9,274 controls, de novo mutations 1,077 family trios, copy number 6,882 11,255 we show that individuals with carry significant burden rare, damaging 3,488 genes previously identified as having near-complete depletion loss-of-function variants. In patients who also have intellectual disability, this is concentrated risk associated neurodevelopmental disorders. After excluding known for disorders, variant persists other intolerant variants; although effect notably stronger both it seen do not disability. Together, our results contribute to the without disability support an overlap genetic between
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Andrew J. Pocklington, Elliott Rees, James T.R. Walters, Jun Han, David H. Kavanagh, Kimberly D. Chambert, Peter Holmans, Jennifer L. Moran, Steven A. McCarroll, George Kirov, Michael C. O’Donovan, Michael J. Owen, Novel findings from CNVs implicate inhibitory and excitatory signaling complexes in schizophrenia Neuron. ,vol. 86, pp. 1203- 1214 ,(2015) , 10.1016/J.NEURON.2015.04.022
Michel Guipponi, Federico A. Santoni, Vincent Setola, Corinne Gehrig, Maud Rotharmel, Macarena Cuenca, Olivier Guillin, Dimitris Dikeos, Georgios Georgantopoulos, George Papadimitriou, Logos Curtis, Alexandre Méary, Franck Schürhoff, Stéphane Jamain, Dimitri Avramopoulos, Marion Leboyer, Dan Rujescu, Ann Pulver, Dominique Campion, David P. Siderovski, Stylianos E. Antonarakis, Exome Sequencing in 53 Sporadic Cases of Schizophrenia Identifies 18 Putative Candidate Genes PLOS ONE. ,vol. 9, ,(2014) , 10.1371/JOURNAL.PONE.0112745
Shay Ben-Shachar, Zhishuo Ou, Chad A Shaw, John W Belmont, Millan S Patel, Marybeth Hummel, Stephen Amato, Nicole Tartaglia, Jonathan Berg, V Reid Sutton, Seema R Lalani, A Craig Chinault, Sau W Cheung, James R Lupski, Ankita Patel, None, 22q11.2 Distal Deletion: A Recurrent Genomic Disorder Distinct from DiGeorge Syndrome and Velocardiofacial Syndrome The American Journal of Human Genetics. ,vol. 82, pp. 214- 221 ,(2008) , 10.1016/J.AJHG.2007.09.014
Xiaolin Zhu, Anna C Need, Slavé Petrovski, David B Goldstein, None, One gene, many neuropsychiatric disorders: lessons from Mendelian diseases Nature Neuroscience. ,vol. 17, pp. 773- 781 ,(2014) , 10.1038/NN.3713
Justin Cotney, Rebecca A. Muhle, Stephan J. Sanders, Li Liu, A. Jeremy Willsey, Wei Niu, Wenzhong Liu, Lambertus Klei, Jing Lei, Jun Yin, Steven K. Reilly, Andrew T. Tebbenkamp, Candace Bichsel, Mihovil Pletikos, Nenad Sestan, Kathryn Roeder, Matthew W. State, Bernie Devlin, James P. Noonan, The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment Nature Communications. ,vol. 6, pp. 6404- 6404 ,(2015) , 10.1038/NCOMMS7404
Simon L Girard, Julie Gauthier, Anne Noreau, Lan Xiong, Sirui Zhou, Loubna Jouan, Alexandre Dionne-Laporte, Dan Spiegelman, Edouard Henrion, Ousmane Diallo, Pascale Thibodeau, Isabelle Bachand, Jessie Y J Bao, Amy Hin Yan Tong, Chi-Ho Lin, Bruno Millet, Nematollah Jaafari, Ridha Joober, Patrick A Dion, Si Lok, Marie-Odile Krebs, Guy A Rouleau, Increased exonic de novo mutation rate in individuals with schizophrenia Nature Genetics. ,vol. 43, pp. 860- 863 ,(2011) , 10.1038/NG.886
J L Rapoport, J N Giedd, N Gogtay, Neurodevelopmental model of schizophrenia: update 2012 Molecular Psychiatry. ,vol. 17, pp. 1228- 1238 ,(2012) , 10.1038/MP.2012.23
Ivan Iossifov, Brian J. O’Roak, Stephan J. Sanders, Michael Ronemus, Niklas Krumm, Dan Levy, Holly A. Stessman, Kali T. Witherspoon, Laura Vives, Karynne E. Patterson, Joshua D. Smith, Bryan Paeper, Deborah A. Nickerson, Jeanselle Dea, Shan Dong, Luis E. Gonzalez, Jeffrey D. Mandell, Shrikant M. Mane, Michael T. Murtha, Catherine A. Sullivan, Michael F. Walker, Zainulabedin Waqar, Liping Wei, A. Jeremy Willsey, Boris Yamrom, Yoon-ha Lee, Ewa Grabowska, Ertugrul Dalkic, Zihua Wang, Steven Marks, Peter Andrews, Anthony Leotta, Jude Kendall, Inessa Hakker, Julie Rosenbaum, Beicong Ma, Linda Rodgers, Jennifer Troge, Giuseppe Narzisi, Seungtai Yoon, Michael C. Schatz, Kenny Ye, W. Richard McCombie, Jay Shendure, Evan E. Eichler, Matthew W. State, Michael Wigler, The contribution of de novo coding mutations to autism spectrum disorder Nature. ,vol. 515, pp. 216- 221 ,(2014) , 10.1038/NATURE13908
Lyudmila Georgieva, Elliott Rees, Priit Palta, Douglas M. Ruderfer, Noa Carrera, Isla Humphreys, Jessica S. Johnson, Panos Roussos, Douglas D. Barker, Eric Banks, Vihra Milanova, Seth G. Grant, Eilis Hannon, Samuel A. Rose, Kimberly Chambert, Milind Mahajan, Edward M. Scolnick, Jennifer L. Moran, George Kirov, Aarno Palotie, Steven A. McCarroll, Peter Holmans, Pamela Sklar, Michael J. Owen, Shaun M. Purcell, Michael C. O’Donovan, Menachem Fromer, Andrew J. Pocklington, David H. Kavanagh, Hywel J. Williams, Sarah Dwyer, Padhraig Gormley, De novo mutations in schizophrenia implicate synaptic networks Nature. ,vol. 506, pp. 179- 184 ,(2014) , 10.1038/NATURE12929
Helen V. Firth, Shola M. Richards, A. Paul Bevan, Stephen Clayton, Manuel Corpas, Diana Rajan, Steven Van Vooren, Yves Moreau, Roger M. Pettett, Nigel P. Carter, DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources American Journal of Human Genetics. ,vol. 84, pp. 524- 533 ,(2009) , 10.1016/J.AJHG.2009.03.010