双相情感障碍和精神分裂症中新生 CNV 的高频出现。
High frequencies of de novo CNVs in bipolar disorder and schizophrenia.
机构信息
Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Neuron. 2011 Dec 22;72(6):951-63. doi: 10.1016/j.neuron.2011.11.007.
Abstract
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.
摘要
虽然已知罕见的拷贝数变异（CNVs）会增加某些神经精神疾病的风险，但 CNVs 在双相情感障碍中的作用尚不清楚。在这里，我们推断 CNVs 对情绪障碍的贡献可能在新生突变中最为明显。我们对 788 个三体型队列中的新生 CNVs 进行了全基因组分析。后代的诊断包括双相情感障碍（n=185）、精神分裂症（n=177）和健康对照（n=426）。与对照组相比，双相情感障碍患者的新生 CNVs 频率明显更高（OR=4.8[1.4,16.0]，p=0.009）。在发病年龄小于 18 岁的病例中，新生 CNVs 特别丰富（OR=6.3[1.7,22.6]，p=0.006）。我们还证实了精神分裂症中新生 CNVs 的显著富集（OR=5.0[1.5,16.8]，p=0.007）。我们的研究结果表明，罕见的自发突变是双相情感障碍和其他主要神经精神疾病风险的重要因素。
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