High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia

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• 作者：Dheeraj Malhotra¹ ; ² ; ²² ; Shane McCarthy²² ; Jacob  ; J. Michaelson¹ ; ² ; Vladimir Vacic¹⁵ ; ²² ; Katherine  ; E. Burdick²³ ; Seungtai Yoon⁵ ; ²² ; Sven Cichon¹⁰ ; ¹¹ ; ¹² ; Aiden Corvin¹⁷ ; Sydney Gary²² ; Elliot  ; S. Gershon²¹ ; Michael Gill¹⁷ ; Maria Karayiorgou¹⁸ ; John  ; R. Kelsoe² ; ⁴ ; ²⁰ ; Olga Krastoshevsky¹⁹ ; Verena Krause¹⁹ ; Ellen Leibenluft⁷ ; Deborah  ; L. Levy¹⁹ ; Vladimir Makarov⁵ ; ²² ; Abhishek Bhandari¹ ; ² ; ²² ; Anil  ; K. Malhotra⁶ ; Francis  ; J. McMahon¹⁴ ; Markus  ; M. Nö ; then¹⁰ ; ¹¹ ; ¹⁶ ; James  ; B. Potash⁸ ; Marcella Rietschel¹³ ; Thomas  ; G. Schulze⁹ ; Jonathan Sebat¹ ; ² ; ³ ; ⁴ ; ²² ; ^{jsebat@ucsd.edu}
• 刊名：Neuron
• 出版年：2011
• 出版时间：22 December 2011
• 年：2011
• 卷：72
• 期：6
• 页码：951-963
• 全文大小：1406 K

文摘

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Summary

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.