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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support SIMILAR CONTENT BEING VIEWED BY OTHERS EXOME SEQUENCING IN BIPOLAR DISORDER IDENTIFIES _AKAP11_ AS A RISK GENE SHARED WITH SCHIZOPHRENIA Article 11 April 2022 RARE LOSS-OF-FUNCTION

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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

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work was supported by grants from 1R01MH081804-01 (NIMH), NARSAD, the Eklund family and the Geraldi Norton Foundation. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Psychiatry

and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA D Zhang, L Cheng, Y Qian, N Alliey-Rodriguez, C Liu & E S Gershon * Department of Psychiatry, University of

California, San Diego, La Jolla, CA, USA J R Kelsoe, T Greenwood, C Nievergelt, T B Barrett & R McKinney * Department of Molecular and Experimental Medicine, The Scripps Research

Institute, La Jolla, CA, USA N Schork, E N Smith & C Bloss * Scripps Genomic Medicine and Scripps Translational Science Institute, La Jolla, CA, USA N Schork, E N Smith & C Bloss *

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA J Nurnberger & D Koller * Department of Biochemistry and Molecular Biology, Indiana University

School of Medicine, Indianapolis, IN, USA H J Edenberg * Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA H J Edenberg & T

Foroud * Department of Psychiatry, Rush University, Chicago, IL, USA W Sheftner * Department of Psychiatry, Howard University, Washington, DC, USA W B Lawson, E A Nwulia & M Hipolito *

Department of Psychiatry, University of Iowa, Iowa City, IA, USA W Coryell * Division of Biosiatistics, Washington University, St Louis, MO, USA J Rice * Department of Psychiatry, University

of California, San Francisco, CA, USA W Byerley * US Department of Health and Human Services, Genetic Basis of Mood and Anxiety Disorders Unit, National Institute of Mental Health

Intramural Research Program, National Institutes of Health, Bethesda, MD, USA F McMahon & T G Schulze * Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA W

Berrettini * Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA J B Potash, P L Belmonte & P P Zandi * Department of Psychiatry, University of Michigan, Ann

Arbor, MI, USA M G McInnis & S Zöllner * Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, USA D Craig & S Szelinger * Department of Human Genetics,

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ARTICLE 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 Download citation * Received: 26 November 2008 * Accepted: 02 December 2008 * Published: 30 December 2008 * Issue Date: April 2009 * DOI:

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available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * copy number variation * singleton * bipolar disorder * genetics