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De Novo Coding Variants Are Strongly Associated with Tourette Disorder
- Source :
- Neuron, vol 94, iss 3
- Publication Year :
- 2017
- Publisher :
- eScholarship, University of California, 2017.
-
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.
- Subjects :
- Parents
Adult
Male
TIC Genetics
Cell Cycle Proteins
TSAICG
Cohort Studies
Tourette Syndrome Association International Consortium for Genetics
Clinical Research
Receptors
Odds Ratio
Genetics
Humans
2.1 Biological and endogenous factors
Psychology
Genetic Predisposition to Disease
whole-exome sequencing
Aetiology
Child
Tourette disorder
de novo variants
Tourette International Collaborative Genetics
Neurology & Neurosurgery
Tourette syndrome
Human Genome
Intracellular Signaling Peptides and Proteins
Neurosciences
Proteins
Genetic Variation
DNA
gene discovery
Cadherins
Phosphoproteins
Fibronectins
Brain Disorders
Cell Surface
Mutation
Female
Cognitive Sciences
Sequence Analysis
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Neuron, vol 94, iss 3
- Accession number :
- edsair.od.......325..094dc2715bec6dedfd3b2ef2a552b929