Narrowing the Boundaries of the Genetic Architecture of Schizophrenia

Wray, Naomi R. and Visscher, Peter M. (2010) Narrowing the Boundaries of the Genetic Architecture of Schizophrenia. Schizophrenia Bulletin, 36 1: 14-23. doi:10.1093/schbul/sbp137


Author Wray, Naomi R.
Visscher, Peter M.
Title Narrowing the Boundaries of the Genetic Architecture of Schizophrenia
Journal name Schizophrenia Bulletin   Check publisher's open access policy
ISSN 0586-7614
1745-1701
Publication date 2010
Year available 2010
Sub-type Article (original research)
DOI 10.1093/schbul/sbp137
Open Access Status
Volume 36
Issue 1
Start page 14
End page 23
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2010
Language eng
Formatted abstract
Genetic architecture of a disease comprises the number, frequency, and effect sizes of genetic risk alleles and the way in which they combine together. Before the genomic revolution, the only clue to underlying genetic architecture of schizophrenia came from the recurrence risks to relatives and the segregation patterns within families. From these clues, very simple genetic architectures could be rejected, but many architectures were consistent with the observed family data. The new era of genome-wide association studies can provide further clues to the genetic architecture of schizophrenia. We explore models of genetic architecture by description rather than the mathematics that underpins them. We conclude that the new genome-wide data allow us to narrow the boundaries on the models of genetic architecture that are consistent with the observed data. A genetic architecture of many common variants of moderate (relative risk > approximately 1.2) can be excluded, yet there is evidence that current generation genome-wide chips do tag an important proportion of the genetic variation for schizophrenia and that the underlying causal variants will include common variants of small effect as well as rarer variants of larger effect. Together, these observations imply that the total number of genetic variants is very large - of the order of thousands. The first generation of studies have generated hypotheses that should be testable in the near future and will further narrow the boundaries on genetic architectures that are consistent with empirical data.
Keyword Complex genetic disease
Genetic architecture
Polygenic
Schizophrenia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes For ERA

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Thu, 23 Oct 2014, 16:54:46 EST by Debra McMurtrie on behalf of Queensland Brain Institute