Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Perinatal Depression: Embracing Variability toward Better Treatment and Outcomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The cost of brain diseases: a burden or a challenge?

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Endogenous cortical rhythms determine cerebral specialization for speech perception and production.

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Tourette International Collaborative Genetics (TIC Genetics)
  • Tourette Syndrome Association International Consortium for Genetics (TSAICG)
View graph of relations

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.

Original languageEnglish
JournalNeuron
Volume94
Issue number3
Pages (from-to)486-499.e9
Number of pages14
ISSN0896-6273
DOIs
Publication statusPublished - 3 May 2017

    Research areas

  • Adult, Cadherins, Child, Cohort Studies, Female, Fibronectins, Genetic Predisposition to Disease, Genetic Variation, Humans, Intracellular Signaling Peptides and Proteins, Male, Mutation, Odds Ratio, Parents, Phosphoproteins, Proteins, Receptors, Cell Surface, Sequence Analysis, DNA, Tourette Syndrome, Journal Article, Video-Audio Media

ID: 51533103