High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia by Malhotra Dheeraj, McCarthy Shane, Michaelson Jacob J, Vacic Vladimir, Burdick Katherine E, Yoon Seungtai, Cichon Sven, Corvin Aiden, Gary Sydney, Gershon Elliot S, Gill Michael, Karayiorgou Maria, Kelsoe John R, Krastoshevsky Olga, Krause Verena, Leibenluft Ellen, Levy Deborah L, Makarov Vladimir, Bhandari Abhishek, Malhotra Anil K, McMahon Francis J, Nöthen Markus M, Potash James B, Rietschel Marcella, Schulze Thomas G, Sebat Jonathan in Neuron (2011).

[PMID: 22196331] PubMed


While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

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