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Cited by 438Schizophrenia research and treatmentGenomic variations and chromosomal abnormalitiesGenomics and Rare Diseases

Increased exonic de novo mutation rate in individuals with schizophrenia

Girard, Simon L, Gauthier, Julie, Noreau, Anne, Xiong, Lan, Zhou, Sirui, Jouan, Loubna, Dionne-Laporte, Alexandre, Spiegelman, Dan +14 more·2011·Nature Genetics
DOI 10.1038/ng.886
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Abstract

Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies. Although schizophrenia heritability may be as high as ∼80%, the genes responsible for much of this heritability remain to be identified. Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate. In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance. Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis.

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Crossref · 10.1038/ng.886

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  • The same principles used in CNV study designs apply to any mutation discovery platform, including exome and whole-genome sequencing.

    “Although these approaches were popularized in the context of CNV studies, the same principles apply to any mutation discovery platform, including exome and whole genome sequencing, as exemplified by the first exome studies in ASD and schizophrenia (Girard et al., 2011; O’Roak et al., 2011; Xu et al., 2011).”

    From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Girard et al., 2011

  • Pioneering exome studies of ASD and schizophrenia have begun with a strong focus on de novo mutations in trios, with compelling preliminary results.

    “Indeed the pioneering exome studies of ASD and schizophrenia have begun with a strong focus on de novo mutations in trios, with compelling preliminary results (Girard et al., 2011; O’Roak et al., 2011; Vissers et al., 2010; Xu et al., 2011).”

    From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Girard et al., 2011

  • High-throughput sequencing efforts are currently under way to sequence exomes and whole genomes in all major psychiatric disorders.

    “The era of high-throughput sequencing is now in full swing, with efforts currently under way to sequence exomes and whole genomes in all major psychiatric disorders (Girard et al., 2011; Najmabadi et al., 2011; O’Roak et al., 2011; Vissers et al., 2010; Xu et al., 2011).”

    From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Girard et al., 2011

  • Preliminary studies have found evidence that the exomic burden of de novo point mutations is increased in schizophrenia.

    “Indeed, preliminary studies of a small number of families have found evidence that the exomic burden of de novo point mutations is increased in schizophrenia (Girard et al., 2011 and Xu et al., 2011).”

    From High frequencies of de novo CNVs in bipolar disorder and schizophrenia (2011) · cites this paper as Girard et al., 2011

  • Two small exome sequencing studies reported rates of putatively functional mutations that exceeded null expectations in SCZ cases, although the rate of de novo point mutations was not elevated in cases and specific genes were not identified.

    “Two small exome sequencing studies 56,57 reported rates of putatively functional mutations that exceeded null expectations in SCZ cases (although the rate of de novo point mutations was not elevated in cases and specific genes were not identified).”

    From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [56]

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Authors
Girard, S. L., Gauthier, J., Noreau, A., Xiong, L., Zhou, S., Jouan, L., Dionne-Laporte, A., Spiegelman, D., Henrion, E., Diallo, O., Thibodeau, P., Bachand, I., Bao, J. Y. J., Tong, A. H. Y., Lin, C.-H., Millet, B., Jaafari, N., Joober, R., Dion, P. A., Lok, S., Krebs, M.-O., & Rouleau, G. A.
Affiliations
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Centre Hospitalier Universitaire Sainte-Justine (CA)
  • University of Hong Kong (HK)
  • Inserm (FR)
  • Douglas Mental Health University Institute (CA)
Corresponding author
Rouleau, Guy A
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2011-07-10
Volume
43
Issue
9
Pages
860-863
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.886
OpenAlex
W2001188663
Cited by
438
References
30
Citations by year
2026: 3 · 2025: 10 · 2024: 8 · 2023: 7 · 2022: 11 · 2021: 13 · 2020: 14 · 2019: 36 · 2018: 26 · 2017: 37 · 2016: 41 · 2015: 39 · 2014: 52 · 2013: 48 · 2012: 57
FWCI
41.72
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (RMF92086)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
schizophrenia, de novo mutations, exome sequencing, nonsense mutation, genetic etiology, heritability, pathogenesis, parent-offspring comparison
MeSH terms
DNA Mutational Analysis, Exons, Humans, Mutation, Pedigree, Schizophrenia

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