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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
Neuron (Cambridge, Mass.), 12/2011, Volume: 72, Issue: 6Journal Article
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. ► Strong association of rare de novo CNVs with bipolar disorder ► Rare de novo CNVs influence age at disease onset in bipolar disorder ► Replication of earlier findings of a high frequency of de novo CNVs in schizophrenia
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