Back to Search
Start Over
Exome sequencing in schizophrenia-affected parent–offspring trios reveals risk conferred by protein-coding de novo mutations
- Source :
- Nature neuroscience, vol 23, iss 2, Nature neuroscience
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas schizophrenia (SCZ) risk associated with DNMs has thus far been shown to be modest. We analyzed DNMs from 1,695 SCZ-affected trios and 1,077 published SCZ-affected trios to better understand the contribution to SCZ risk. Among 2,772 SCZ probands, exome-wide DNM burden remained modest. Gene set analyses revealed that SCZ DNMs were significantly concentrated in genes that were highly expressed in the brain, that were under strong evolutionary constraint and/or overlapped with genes identified in other neurodevelopmental disorders. No single gene surpassed exome-wide significance; however, 16 genes were recurrently hit by protein-truncating DNMs, corresponding to a 3.15-fold higher rate than the mutation model expectation (permuted 95% confidence interval: 1-10 genes; permuted P = 3 × 10-5). Overall, DNMs explain a small fraction of SCZ risk, and larger samples are needed to identify individual risk genes, as coding variation across many genes confers risk for SCZ in the population.
- Subjects :
- Parents
Adult
Male
0301 basic medicine
Proband
Population
Biology
medicine.disease_cause
Article
Whole Exome Sequencing
03 medical and health sciences
0302 clinical medicine
Clinical Research
Exome Sequencing
Genetics
medicine
2.1 Biological and endogenous factors
Humans
Psychology
Genetic Predisposition to Disease
Family
Aetiology
Child
education
Gene
De novo mutations
Exome sequencing
Protein coding
education.field_of_study
Mutation
Neurology & Neurosurgery
General Neuroscience
Human Genome
Neurosciences
Serious Mental Illness
medicine.disease
Brain Disorders
Mental Health
030104 developmental biology
Schizophrenia
Female
Cognitive Sciences
Neuroscience
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 15461726 and 10976256
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Nature Neuroscience
- Accession number :
- edsair.doi.dedup.....3fb0ae74a8b115c5e58b61cb08005427