Schizophrenia genetics: the search for a hard lead - PubMed (original) (raw)
Review
Schizophrenia genetics: the search for a hard lead
Patrick F Sullivan. Curr Opin Psychiatry. 2008 Mar.
Abstract
Purpose of review: To describe the rationale for searching for genes for schizophrenia, prior efforts via candidate gene association and genomewide linkage studies, and to set the stage for the numerous genomewide association studies that will emerge by the end of 2008.
Recent findings: Genomewide association studies have identified dozens of new and previously unsuspected candidate genes for many biomedical disorders. At least seven new studies of approximately 20,000 cases plus controls are expected to be completed by the end of 2008.
Summary: Current results have few implications for clinical practice or research, and it is possible that this recommendation could be dramatically different in a year.
Figures
Figure 1
Shows an example of an association study for one genetic marker. The genetic marker is the “famous” COMT val158met polymorphism located on chromosome 22 at base pair position 18,325,825. A “G” at this position codes for valine and an “A” codes for methionine. At the top of the Figure, DNA in the immediate vicinity of rs4680 is shown with the actual variant in larger font size. The DNA sequences on either side are the “keys” that allow the specific interrogation of rs4680 using PCR as the combination of the left and right sequences are found exactly once in the human genome. People usually have two copies of chr22, one from each parent. Each of the copies of chr22 could have either an A or a G at position 18,325,825. Thus, these two “alleles” make up a “genotype”. Case #1 inherited an A and a G – also know as alleles A and G and genotype A/G. Case #2 inherited a G from each parent and has two copies of allele G and genotype G/G. The basic test for an association between case/control status and rs4680 genotype is a 2 × 3 contingency table with the cells containing genotype counts. There is no significant association between case/control status and rs4680 genotype in this example.
References
- Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry. 2003;60:1187–92. - PubMed
- Plomin R, DeFries JC, Craig IW, McGuffin P. Behavioral Genetics in the Postgenomic Era. 3rd ed. APA Books; Washington, DC: 2003.
- Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genetics. 2003;33:177–82. - PubMed
- Ioannidis JP. Commentary: Grading the credibility of molecular evidence for complex diseases. Int J Epidemiol. 2006;35:572–8. - PubMed
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