Is there an association between NPY and neuroticism?


Arising from: Z. Zhou et al. Nature 452, 997–1001 (2008)10.1038/nature06858; Zhou et al. reply

Psychiatric genetics has been hampered by the fact that initially exciting findings from underpowered studies are so often not replicated in larger, more powerful, data sets. Here we show that the claims of Zhou et al.1 that neuropeptide Y (NPY) diplotype-predicted expression is correlated with trait anxiety (neuroticism) is not replicated in a data set consisting of phenotypically extreme individuals drawn from a large (n = 88,142) non-clinical population. We found no association between NPY diplotype or diplotype-predicted expression and neuroticism. Our reply to Zhou and colleagues forms part of a larger debate2,3,4,5 (see, for example, about the efficacy and replicability of candidate driven versus genome wide approaches to psychiatric genetics.

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Figure 1: Diplotype-predicted NPY expression and neuroticism.


  1. 1

    Zhou, Z. et al. Genetic variation in human NPY expression affects stress response and emotion. Nature 452, 997–1001 (2008)

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    Munafo, M. R., Bowes, L., Clark, T. G. & Flint, J. Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol. Psychiatry 10, 765–770 (2005)

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    Abbott, A. Psychiatric genetics: The brains of the family. Nature 454, 154–157 (2008)

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    Gabriel, S. & Ziaugra, L. SNP genotyping using Sequenom MassARRAY 7K platform. Curr. Protoc. Hum. Genet. Chapter 2 Unit 2.12 (2004)| Article | PubMed |

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Cotton, C., Flint, J. & Campbell, T. Is there an association between NPY and neuroticism?. Nature 458, E6 (2009).

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