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Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

by Jeremy, Willsey A , Xing Jinchuan , Morer Astrid , Thackray, Joshua K , Gilbert, Donald L , Münchau Alexander , Kuperman, Samuel , Dietrich, Andrea , Fernandez, Thomas V , Leventhal, Bennett L , Dong-Ho, Song , Zinner, Samuel H , State, Matthew W , Nasello Cara , Young-Shin, Kim , Brown, Lawrence W , Heyman Isobel , Roessner Veit , Maras Athanasios , Hedderly Tammy , Madruga-Garrido Marcos , King, Robert A , Plessen, Kerstin J , Tischfield Jay A , Garcia-Delgar, Blanca , Mohamed, Abdulkadir , Hoekstra, Pieter J , Hagstrøm, Julie , Zhou, Lisheng , Kim, Eunjoo , Yun-Joo, Koh , Deng, Li , Zhang Yeting , Koesterich Justin , Mir, Pablo , Cao Xiaolong , Huyser Chaim , Heiman, Gary A , Coffey, Barbara J

in Cadherins / Dynein / Etiology / Gene expression / Genetic diversity / Genotyping / Neurodevelopmental disorders / Next-generation sequencing / Palmitoyltransferase / Serine peptidase / Tourette syndrome / Zinc finger proteins

2021

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Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

2021

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2021

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Journal Article

Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Jeremy, Willsey A,

Xing Jinchuan,

Morer Astrid,

Thackray, Joshua K,

Gilbert, Donald L,

Münchau Alexander,

Kuperman, Samuel,

Dietrich, Andrea,

Fernandez, Thomas V,

Leventhal, Bennett L,

Dong-Ho, Song,

Zinner, Samuel H,

State, Matthew W,

Nasello Cara,

Young-Shin, Kim,

Brown, Lawrence W,

Heyman Isobel,

Roessner Veit,

Maras Athanasios,

Hedderly Tammy,

Madruga-Garrido Marcos,

King, Robert A,

Plessen, Kerstin J,

Tischfield Jay A,

Garcia-Delgar, Blanca,

Mohamed, Abdulkadir,

Hoekstra, Pieter J,

Hagstrøm, Julie,

Zhou, Lisheng,

Kim, Eunjoo,

Yun-Joo, Koh,

Deng, Li,

Zhang Yeting,

Koesterich Justin,

Mir, Pablo,

Cao Xiaolong,

Huyser Chaim,

Heiman, Gary A,

Coffey, Barbara J

2021

Overview

Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

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Publisher

Nature Publishing Group

Subject

/ Dynein

/ Neurodevelopmental disorders