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DCNP1: a novel candidate gene for major depression

Molecular Psychiatry volume 11, pages 121–122 (2006)Cite this article

Over the last decade hypothesis-driven candidate gene studies have come to dominate psychiatric genetics research. However, despite this proliferation, to date few genetic effects have been successfully identified and independently replicated.1 One of the factors limiting the success of this approach is likely to be fine-scale variation in linkage disequilibrium (LD) across the gene of interest. Incomplete correlation between the genotyped marker and causative variant will reduce the available statistical power and limit the capacity for detecting small effects.2 In order to circumvent these difficulties, potential candidate genes can be prioritised in terms of variant functionality, thereby increasing the probability that the genotyped marker is the disease-causing variant. With the advent of large-scale sequencing projects such as HAPMAP,3 it is now possible to select variants for analysis from large publicly available databases on the basis of their predicted consequences and the expression patterns of their host gene. Here we briefly describe an application of this method, and report the identification of a single gene that associates with self-report lifetime major depression (MD) history (defined according to DSM-IV criteria 4).

We generated a composite list of single nucleotide polymorphisms (SNPs) derived from NCBI and Ensembl, and annotated as causing de novo stop or splice sites in either one or both databases. These SNPs were then parsed for evidence of validation, and the resulting variants (premature termination n=501, splice variant n=186) subject to a literature search for evidence of neural expression and/or involvement in a neurobehavioural trait. A total of 25 potential candidates were identified. These SNPs were genotyped on a Sequenom platform in a large sample of singletons (n=918) selected from a south-west England community cohort (n=88,142) on the basis of extremity of Neuroticism score (a continuous phenotype which is estimated to share around 55% of its genetic liability with MD5). Details of sample selection and data collection are provided elsewhere.6, 7

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  1. Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN, UK

    S A G Willis-Owen, S Shifman, R R Copley & J Flint

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  1. S A G Willis-Owen
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  2. S Shifman
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  3. R R Copley
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  4. J Flint
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Willis-Owen, S., Shifman, S., Copley, R. et al. DCNP1: a novel candidate gene for major depression. Mol Psychiatry 11, 121–122 (2006). https://doi.org/10.1038/sj.mp.4001747

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