De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Details
Serval ID
serval:BIB_B65501FF10F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Journal
Neuron
Working group(s)
Tourette International Collaborative Genetics (TIC Genetics), Tourette Syndrome Association International Consortium for Genetics (TSAICG)
Contributor(s)
Abdulkadir M., Bohnenpoll J., Bromberg Y., Brown L.W., Cheon K.A., Coffey B.J., Deng L., Dietrich A., Dong S., Elzerman L., Fernandez T.V., Fründt O., Garcia-Delgar B., Gedvilaite E., Gilbert D.L., Grice D.E., Hagstrøm J., Hedderly T., Heiman G.A., Heyman I., Hoekstra P.J., Hong H.J., Huyser C., Ibanez-Gomez L., Kim Y.K., Kim Y.S., King R.A., Koh Y.J., Kook S., Kuperman S., Lamerz A., Leventhal B., Ludolph A.G., Lühr da Silva C., Madruga-Garrido M., Mandell J.D., Maras A., Mir P., Morer A., Münchau A., Murphy T.L., Nasello C., Openneer TJC, Plessen K.J., Richer P., Roessner V., Sanders S., Shin E.Y., Sival D.A., Smith L., Song D.H., Song J., State M.W., Stolte A.M., Sun N., Tischfield J.A., Tübing J., Visscher F., Walker M.F., Wanderer S., Wang S., Willsey A.J., Woods M., Xing J., Zhang Y., Zhou A., Zinner S.H., 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., MaMahon 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
1097-4199 (Electronic)
ISSN-L
0896-6273
Publication state
Published
Issued date
03/05/2017
Peer-reviewed
Oui
Volume
94
Number
3
Pages
486-499.e9
Language
english
Notes
Publication types: Journal Article ; Video-Audio Media
Publication Status: ppublish
Publication Status: ppublish
Abstract
Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. VIDEO ABSTRACT.
Keywords
Adult, Cadherins/genetics, Child, Cohort Studies, Female, Fibronectins/genetics, Genetic Predisposition to Disease, Genetic Variation, Humans, Intracellular Signaling Peptides and Proteins/genetics, Male, Mutation, Odds Ratio, Parents, Phosphoproteins/genetics, Proteins/genetics, Receptors, Cell Surface/genetics, Sequence Analysis, DNA, Tourette Syndrome/genetics, TIC Genetics, TSAICG, Tourette disorder, Tourette syndrome, de novo variants, gene discovery, whole-exome sequencing
Pubmed
Create date
14/02/2019 9:51
Last modification date
20/08/2019 16:24
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