De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.
Details
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_916205B4C8EC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.
Journal
Cell reports
Working group(s)
Tourette International Collaborative Genetics Study (TIC Genetics), Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE), Tourette Association of America International Consortium for Genetics (TAAICG)
Contributor(s)
Abdulkadir M., Arbelaez J., Bodmer B., Bromberg Y., Brown L.W., Cheon K.A., Coffey B.J., Deng L., Dietrich A., Dong S., Duhn C., Elzerman L., Fernandez T.V., Fremer C., Garcia-Delgar B., Gilbert D.L., Grice D.E., Hagstrøm J., Hedderly T., Heiman G.A., Heyman I., Hoekstra P.J., Hong H.J., Huyser C., Kim E.J., Kim Y.K., Kim Y.S., King R.A., Koh Y.J., Kook S., Kuperman S., Leventhal B.L., Ludolph A.G., Madruga-Garrido M., Mandell J.D., Maras A., Mir P., Morer A., Morris M.T., Müller-Vahl K., Münchau A., Murphy T.L., Nasello C., Plessen K.J., Poisner H., Roessner V., Sanders S.J., Shin E.Y., Song D.H., Song J., State M.W., Sun N., Thackray J.K., Tischfield J.A., Tübing J., Visscher F., Wanderer S., Wang S., Willsey A.J., Woods M., Xing J., Zhang Y., Zhao X., Zinner S.H., Androutsos C., Barta C., Farkas L., Fichna J., Georgitsi M., Janik P., Karagiannidis I., Koumoula A., Nagy P., Paschou P., Puchala J., Rizzo R., Szejko N., Szymanska U., Tarnok Z., Tsironi V., Wolanczyk T., Zekanowski C., Barr C.L., Batterson J.R., Berlin C., Bruun R.D., Budman C.L., Cath D.C., Chouinard S., Coppola G., Cox N.J., Darrow S., Davis L.K., Dion Y., Freimer N.B., Grados M.A., Hirschtritt M.E., Huang A.Y., Illmann C., King R.A., Kurlan R., Leckman J.F., Lyon G.J., Malaty I.A., Mathews C.A., MacMahon W.M., Neale B.M., Okun M.S., Osiecki L., Pauls D.L., Posthuma D., Ramensky V., Robertson M.M., Rouleau G.A., Sandor P., Scharf J.M., Singer H.S., Smit J., Sul J.H., Yu D.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
25/09/2018
Peer-reviewed
Oui
Volume
24
Number
13
Pages
3441-3454.e12
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk.
Keywords
Adult, Cadherins/genetics, Cell Polarity, Child, DNA Copy Number Variations, Female, Humans, Male, Pedigree, Receptors, Cell Surface/genetics, Tourette Syndrome/genetics, Tourette Syndrome/pathology, TIC Genetics, Tourette disorder, cell polarity, copy number variants, de novo variants, gene discovery, microarray genotyping, multiplex, simplex, whole exome sequencing
Pubmed
Web of science
Open Access
Yes
Create date
22/04/2020 10:30
Last modification date
25/04/2020 6:09
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