Penetrance for copy number variants associated with schizophrenia
Penetrance for copy number variants associated with schizophrenia
复制标题
DOI：
10.1093/hmg/ddq259
复制
发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Lewis, Cathryn M.
中科院分区：
文献类型：
--
作者：
Vassos, Evangelos;Collier, David A.;Lewis, Cathryn M.
与精神分裂症等神经精神疾病相关的高风险新拷贝数变异(CNV)的发现为临床遗传学家提供了将这些发现转化为有用工具的机会。然而，这将需要对这些变体的外显率进行估计，这一点尚未得到适当的考虑。为了促进这一过程，我们使用一种新的贝叶斯方法对已发表的病例对照研究的汇总数据进行了估计，与精神分裂症相关的CNV的外显率分别为15q13.3、1q21.1、15q11.2、17p12、2p16.3、16p13.1和16p11.2。对于这些CNV，精神分裂症的外显率在2%到7.4%之间，而在速度-心面综合征中发现的22q11.2缺失对精神分裂症的外显率要高得多。15q13.3缺失的外显率最高(个体研究中为6-9%)，15q11.2的外显率最低(2%)。CNV比普通变种患精神分裂症的风险高得多，但它们的外显率大大低于孟德尔障碍或其他综合征。由于这些CNV易患多种疾病，包括癫痫、自闭症和智能障碍，因此外显率估计也需要考虑诊断特异性，而且它们对任何神经精神疾病的总体外显率可能要高得多。因此，尽管CNV仍远未在临床上有用或与特定疾病的遗传咨询有关，但它们的检测在预测阴性发育结果方面可能具有重要的临床价值。
The discovery of 'high-risk' de novo copy number variants (CNVs) associated with neuropsychiatric disorders such as schizophrenia offers the opportunity to translate these findings into useful tools for clinical geneticists. However, this will require estimation of penetrance for these variants, which has not yet been properly considered. To facilitate this process, we estimated the penetrance of CNVs associated with schizophrenia, at 15q13.3, 1q21.1, 15q11.2, 17p12, 2p16.3, 16p13.1 and 16p11.2 with a novel Bayesian method applied to pooled data from published case-control studies. For these CNVs, penetrance for schizophrenia was between 2 and 7.4%, which contrasts with the much higher penetrance for schizophrenia of the 22q11.2 deletions found in velo-cardio-facial syndrome. The highest penetrance was for 15q13.3 deletion (6-9% in individual studies) and the lowest was for 15q11.2 (2%). CNVs confer much higher risk for schizophrenia than common variants, but their penetrance is substantially lower than Mendelian disorders or other syndromic conditions. Since these CNVs predispose to multiple disorders, including epilepsy, autism and intellectual impairment, penetrance estimates will also need to take into account diagnostic specificity, and their overall penetrance for any neuropsychiatric disorder is likely to be much higher. Thus, although CNVs are still far from being clinically useful or relevant to genetic counselling for specific disorders, their detection may hold an important clinical value in predicting negative developmental outcomes.