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Brief Communication Arising

Nature 458, E6 (2 April 2009) | doi:10.1038/nature07927; Received 11 November 2008; Accepted 11 February 2009

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Is there an association between NPY and neuroticism?

Colleen H. Cotton1, Jonathan Flint1 & Thomas G. Campbell1,2

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Arising from: Z. Zhou et al. Nature 452, 997–1001 (2008); 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, http://www.nature.com/news/2008/080709/full/454154a.html) about the efficacy and replicability of candidate driven versus genome wide approaches to psychiatric genetics.