Cited by 298Schizophrenia research and treatmentGenetic Associations and EpidemiologyGenomic variations and chromosomal abnormalities

Schizophrenia: a common disease caused by multiple rare alleles

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McClellan, Jon M., Susser, Ezra, King, Mary-Claire·2007·British Journal of Psychiatry

Abstract

Summary: Schizophrenia is widely held to stem from the combined effects of multiple common polymorphisms, each with a small impact on disease risk. We suggest an alternative view: that schizophrenia is highly heterogeneous genetically and that many predisposing mutations are highly penetrant and individually rare, even specific to single cases or families. This ‘common disease – rare alleles' hypothesis is supported by recent findings in human genomics and by allelic and locus heterogeneity for other complex traits. We review the implications of this model for gene discovery research in schizophrenia.

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  • Schizophrenia may be a collection of hundreds or thousands of similar conditions attributable to rare variants at individual loci.

    “The notion is that a disease such as schizophrenia is actually a collection of hundreds, or possibly even thousands, of similar conditions attributable to rare variants at individual loci18.”

    From Rare and common variants: twenty arguments (2012) · cites this paper as [18]

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  1. Maynard, T. M., Haskell, G. T., Lieberman, J. A., Maynard, T. M., Haskell, G. T., Lieberman, J. A., et al et al (2002) (2002) 22q11DS: genomic mechanisms andgene function 22q11DS: genomic mechanisms andgene function in DiGeorge/velocardiofacialsyndrome. in DiGeorge/velocardiofacial syndrome.International International Journal of Developmental Neuroscience Journal of Developmental Neuroscience, , 20 20,407^419. ,407^419.

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Authors
McClellan, J. M., Susser, E., & King, M.-C.
Affiliations
  • University of Washington (US)
  • New York State Psychiatric Institute (US)
Corresponding author
McClellan, Jon M.
Venue
British Journal of Psychiatry
Published
2007-03
Volume
190
Issue
3
Pages
194-199
ISSN
  • 0007-1250 (ISSN-L)
  • 1472-1465
OpenAlex
W2114381854
Cited by
296
References
85
Citations by year
2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 1 · 2017: 7 · 2016: 13 · 2015: 14 · 2014: 16 · 2013: 24 · 2012: 23
FWCI
5.58
Type
journal article
Language
en
Open access
Locations
  • The British Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k20mh001120-05)
  • National Institute of Mental Health (MH 01120)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
schizophrenia, genetic heterogeneity, locus heterogeneity, allelic heterogeneity, rare mutations, penetrance, genetic susceptibility, gene discovery, complex traits
MeSH terms
Alleles, Humans, Genetic Linkage, Mutation, Nerve Tissue Proteins, Polymorphism, Genetic, RNA, Messenger, Schizophrenia, Genome, Human, Genetic Predisposition to Disease, Biomedical Research, RNA, Long Noncoding

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