CIBER en Epidemiología y Salud Pública (CIBERESP), Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona 08003, Catalonia, Spain.
J Psychiatr Res. 2010 Oct;44(14):971-8. doi: 10.1016/j.jpsychires.2010.03.007. Epub 2010 Apr 15.
Copy number variations (CNV) have become an important source of human genome variability noteworthy to consider when studying genetic susceptibility to complex diseases. As recent studies have found evidences for the potential involvement of CNVs in psychiatric disorders, we have studied the dosage effect of structural genome variants as a possible susceptibility factor for different psychiatric disorders in a candidate gene approach.
After selection of 68 psychiatric disorders' candidate genes overlapping with CNVs, MLPA assays were designed to determine changes in copy number of these genes. The studied sample consisted of 724 patients with psychiatric disorders (accounting for anxiety disorders, mood disorders, eating disorders and schizophrenia) and 341 control individuals.
CNVs were detected in 30 out of the 68 genes screened, indicating that a considerable proportion of neuronal pathways genes contain CNVs. When testing the overall burden of rare structural genomic variants in the different psychiatric disorders compared to control individuals, there was no statistically significant difference in the total amount of gains and losses. However, 14 out of the 30 changes were only found in psychiatric disorder patients but not in control individuals. These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B, SSTR5 and COMT in schizophrenia.
Although we have not been able to found a clear association between the studied CNVs and psychiatric disorders, the rare variants found only within the patients could account for a step further towards understanding the pathophysiology of psychiatric disorders.
拷贝数变异（CNV）已成为人类基因组变异的一个重要来源，在研究复杂疾病的遗传易感性时值得考虑。由于最近的研究发现 CNV 可能与精神障碍有关，我们采用候选基因方法研究了结构基因组变异作为不同精神障碍易感性因素的剂量效应。
在选择了 68 个与 CNV 重叠的精神障碍候选基因后，设计了 MLPA 测定法来确定这些基因的拷贝数变化。研究样本包括 724 名精神障碍患者（包括焦虑障碍、心境障碍、饮食障碍和精神分裂症）和 341 名对照个体。
在所筛选的 68 个基因中，有 30 个检测到 CNV，这表明相当一部分神经元通路基因含有 CNV。当比较不同精神障碍与对照个体之间罕见结构基因组变异的总体负担时，增益和缺失的总量没有统计学上的显著差异。然而，在 30 个变化中，有 14 个仅在精神障碍患者中发现，而在对照个体中没有发现。这些基因包括先前与重度抑郁症和双相情感障碍相关的 GRM7、与焦虑障碍相关的 SLC6A13，以及与精神分裂症相关的 S100B、SSTR5 和 COMT。
尽管我们未能发现所研究的 CNV 与精神障碍之间存在明确的关联，但仅在患者中发现的罕见变异可能进一步解释精神障碍的病理生理学。
