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Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study

Molecular Psychiatry volume 14, pages 804–819 (2009)Cite this article

Abstract

A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334 563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy were identified within the neuronal PAS domain protein 3 gene (NPAS3), close to a translocation breakpoint site previously observed in a family with schizophrenia. Five other loci were identified that include the XK, Kell blood group complex subunit-related family, member 4 gene (XKR4), the tenascin-R gene (TNR), the glutamate receptor, inotropic, AMPA 4 gene (GRIA4), the glial cell line-derived neurotrophic factor receptor-alpha2 gene (GFRA2), and the NUDT9P1 pseudogene located in the chromosomal region of the serotonin receptor 7 gene (HTR7). The study of these polymorphisms and genes may lead to a better understanding of the etiology of schizophrenia and of its treatment. These results provide new insight into response to iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio.

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Acknowledgements

We thank all of the patients who participated in this study. We also thank Michael Di Marino and Ingeborg Holt for their assistance in the statistical analysis and Kelly Greer for her technical support. We are grateful to Dr Yoav Benjamini and Chip Clark for their critical reviews of the paper.

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  1. Vanda Pharmaceuticals Inc., Rockville, MD, USA

    C Lavedan, L Licamele, S Volpi, J Hamilton, C Heaton, K Mack, R Lannan, A Thompson, C D Wolfgang & M H Polymeropoulos

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  1. C Lavedan
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  2. L Licamele
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Correspondence to C Lavedan.

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All authors are employees of Vanda Pharmaceuticals Inc. and have no additional affiliations or financial interests to disclose.

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Lavedan, C., Licamele, L., Volpi, S. et al. Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study. Mol Psychiatry 14, 804–819 (2009). https://doi.org/10.1038/mp.2008.56

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