Neuregulin 1 Genotype and Schizophrenia: study

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The neuregulin 1 (NRG1) gene has been the subject of considerable excitement within the psychiatric genetics literature since it was originally identified as a potential susceptibility locus for schizophrenia. Here we provide an update of our first meta-analysis of this association. Case-control and family-based genetic association studies of the NRG1 gene in healthy control groups and clinically diagnosed schizophrenia patients were included. 

We repeated the search strategy in our earlier meta-analysis for studies published between December 31, 2005, and September 30, 2007, and updated the results of our original meta-analysis accordingly. Superficially, the results of our updated meta-analysis are consistent with those in our previous report, although it is notable that the strength of evidence as based on our haplotype analysis has weakened over this period.

The evidence for association of the SNP8NRG221533 polymorphism continued to be nonsignificant. We discuss a number of problems in the interpretation of a disparate and inconsistent gene-disease association literature, including the difficulties associated with determining what constitutes replication across studies which vary in their methods, marker sets employed, phenotype definition, and other study characteristics.

Marcus R. Munafò, Angela S. Attwood and Jonathan Flint
Department of Experimental Psychology, University of Bristol, 12a Priory Road, Bristol BS8 1TU, UK
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK

Schizophrenia Bulletin Advance Access originally published online on November 20, 2007
Schizophrenia Bulletin 2008 34(1):9-12; doi:10.1093/schbul/sbm129

References

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2. Petryshen TL, Middleton FA, Kirby A, et al. Support for involvement of neuregulin 1 in schizophrenia pathophysiology. Mol Psychiatry (2005) 10::366–374. 328.

3. Munafo MR, Flint J. Meta-analysis of genetic association studies. Trends Genet (2004) 20::439–444.

4. Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG, Ioannidis JP. Establishment of genetic associations for complex diseases is independent of early study findings. Eur J Hum Genet (2004) 12::762–769.

5. Munafo MR, Thiselton DL, Clark TG, Flint J. Association of the NRG1 gene and schizophrenia: a meta-analysis. Mol Psychiatry (2006) 11::539–546.

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7. Hall H, Lawyer G, Sillen A, et al. Potential genetic variants in schizophrenia: a Bayesian analysis. World J Biol Psychiatry (2007) 8::12–22.

Full article

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