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Singleton deletions throughout the genome increase risk of bipolar disorder

Abstract

An overall burden of rare structural genomic variants has not been reported in bipolar disorder (BD), although there have been reports of cases with microduplication and microdeletion. Here, we present a genome-wide copy number variant (CNV) survey of 1001 cases and 1034 controls using the Affymetrix single nucleotide polymorphism (SNP) 6.0 SNP and CNV platform. Singleton deletions (deletions that appear only once in the dataset) more than 100 kb in length are present in 16.2% of BD cases in contrast to 12.3% of controls (permutation P=0.007). This effect was more pronounced for age at onset of mania 18 years old. Our results strongly suggest that BD can result from the effects of multiple rare structural variants.

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Acknowledgements

This paper was prepared as part of the bipolar collaboration of the GAIN, and was submitted before the end of the publication embargo for non-GAIN scientists. We acknowledge Dr Dan Nicolae (University of Chicago) for extensive statistical discussion and advice, Mr Xiaotong Zhang (University of Chicago) for his excellent software support and Ms Kay Grennan (University of Chicago) for her technical assistance. This work was supported by grants from 1R01MH081804-01 (NIMH), NARSAD, the Eklund family and the Geraldi Norton Foundation.

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Correspondence to C Liu or E S Gershon.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Zhang, D., Cheng, L., Qian, Y. et al. Singleton deletions throughout the genome increase risk of bipolar disorder. Mol Psychiatry 14, 376–380 (2009). https://doi.org/10.1038/mp.2008.144

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