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Investigation of rare non-synonymous variants at ABCA13 in schizophrenia and bipolar disorder

Molecular Psychiatry volume 16, pages 790–791 (2011)Cite this article

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It has recently been reported that rare genetic variants in adenosine triphosphate (ATP)-binding cassette A13 (ABCA13) increase susceptibility to schizophrenia, bipolar disorder and major depression.1 The gene was targeted following the observation of a complex chromosomal rearrangement, inv(7) (p12.3;q21.11), t(7;8)(p12.3;p23) in an individual with severe chronic schizophrenia.1 Only one breakpoint disrupted a gene, that at 7p12.3 to which maps ABCA13. This led the authors to postulate the involvement of rare non-synonymous variants at ABCA13 in major psychiatric disorders. They resequenced the exons of ABCA13 that encode key functional domains in 100 individuals with schizophrenia and 100 controls, and observed a total of 32 novel variants. In all, 10 of these were observed in not more than one control and were predicted to cause a non-conservative amino-acid change and these were tested for involvement in psychiatric disorders using case samples comprising individuals with schizophrenia, bipolar disorder, major depression, as well as controls.

In these follow-up samples, the minor allele was observed in at least one additional case for only six of the markers. Of these, three variants were nominally significantly associated with bipolar disorder and one was nominally significantly associated with schizophrenia (indicated by * and † in Table 1, respectively). Although no variant was significantly associated after correcting for multiple testing, an aggregate test of minor alleles at all 10 loci under the assumption of marker independence revealed that compared with the controls, there was a significant increase in the minor allele load in the schizophrenia (P=0.0057) and the bipolar cohorts (P=7.4 × 10−5). No excess was found in those with major depression. The combined effect size estimated as an odds ratio (OR) of the variants was 1.93 (95% lower CI=1.24) for schizophrenia and 2.71 (95% lower CI=1.73) for bipolar disorder. Across all diagnoses, the combined OR was 2.1 (95% lower CI=1.45).

Table 1 Individual P values (Fishers exact test, 1-tailed) and OR for the minor allele
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Authors and Affiliations

  1. MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK

    S Dwyer, H Williams, I Jones, J Walters, N Craddock, M J Owen & M C O'Donovan

  2. Department of Psychiatry, University of Birmingham, National Centre for Mental Health, Birmingham, UK

    L Jones

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  1. S Dwyer
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  2. H Williams
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  3. I Jones
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  4. L Jones
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  5. J Walters
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  6. N Craddock
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  7. M J Owen
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  8. M C O'Donovan
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Corresponding author

Correspondence to M C O'Donovan.

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Dwyer, S., Williams, H., Jones, I. et al. Investigation of rare non-synonymous variants at ABCA13 in schizophrenia and bipolar disorder. Mol Psychiatry 16, 790–791 (2011). https://doi.org/10.1038/mp.2011.2

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