Translating genetic risk loci into molecular risk mechanisms for schizophrenia

Bray, Nicholas John ORCID: https://orcid.org/0000-0002-4357-574X and Hill, Matthew ORCID: https://orcid.org/0000-0001-6776-8709 2016. Translating genetic risk loci into molecular risk mechanisms for schizophrenia. Schizophrenia Bulletin 42 (1) , pp. 5-8. 10.1093/schbul/sbv156

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Abstract

The past decade has witnessed major advances in our understanding of the genetics of schizophrenia. Large, consortia-led genomic studies involving thousands of patients and controls have identified genetic loci associated with risk for the disorder at unprecedented levels of confidence. As expected from a condition associated with reduced fecundity, variants that have a large impact on risk for schizophrenia are invariably rare, occurring even in patients at frequencies considerably less than 1%. These include copy number variants (CNVs) which delete or duplicate large segments of DNA, often encompassing multiple genes.1 Alleles of strong effect on schizophrenia risk also potentially include loss-of-function de novo mutations within protein coding DNA sequence that have recently been identified through exome sequencing studies.2 It is clear, however, that schizophrenia also involves the action of many genetic variants that are common in the general population (frequencies > 5%). Although these have individually small effects on risk for schizophrenia (odds ratios typically < 1.2), they collectively account for a sizeable fraction of the variance in liability to the disorder.3 In the largest genome-wide association study (GWAS) of schizophrenia to date, the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) reported genome-wide significant association between the disorder and common variation at 108 independent genetic loci.4 In the following short article, we outline some of the questions that first need to be addressed in translating these latter findings into an improved understanding of common molecular risk mechanisms for schizophrenia, and introduce functional genomic technologies that can be applied for this purpose.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Oxford University Press
ISSN:	0586-7614
Last Modified:	31 Oct 2022 10:18
URI:	https://orca.cardiff.ac.uk/id/eprint/84365

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