Publication

De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Tourette Int Collaborative, Tourette Syndrome Genetics & TAAICG, 25-Sep-2018, In : Cell reports. 24, 13, p. 3441-3454.e12 26 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Tourette Int Collaborative
  • Tourette Syndrome Genetics
  • TAAICG

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.

Original languageEnglish
Pages (from-to)3441-3454.e12
Number of pages26
JournalCell reports
Volume24
Issue number13
Publication statusPublished - 25-Sep-2018

    Keywords

  • AUTISM SPECTRUM DISORDER, SEVERE INTELLECTUAL DISABILITY, OBSESSIVE-COMPULSIVE DISORDER, CONGENITAL HEART-DISEASE, NEURODEVELOPMENTAL DISORDERS, MUTATIONS, RARE, GENOME, SCHIZOPHRENIA, PREVALENCE

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