Budde M, Forstner A J, Adorjan K, Schaupp S K, Nöthen M M, Schulze T G
Institut für Psychiatrische Phänomik und Genomik (IPPG), Klinikum der Universität München, Nußbaumstraße 7, 80336, München, Deutschland.
Institut für Humangenetik, Universitätsklinikum Bonn, Bonn, Deutschland.
Nervenarzt. 2017 Jul;88(7):755-759. doi: 10.1007/s00115-017-0336-9.
Bipolar disorder (BD) has a multifactorial etiology. Its development is influenced by genetic as well as environmental factors. Large genome-wide association studies (GWAS), in which genetic risk allelic variants for the disorder could be replicated for the first time, marked the breakthrough in the identification of the responsible risk genes. In addition to these common genetic variants with moderate effects identified by GWAS, rare variants with a higher penetrance are expected to play a role in disease development. The results of recent studies suggest that copy number variants might contribute to BD development, although to a lesser extent than in other psychiatric disorders, such as schizophrenia or autism. Results from the initial next generation sequencing studies indicate an enrichment of rare variants in pathways and genes that were previously found to be associated with BD. In the field of pharmacogenetics, a risk gene that influences the individual variance in the response to lithium treatment was identified for the first time in a recent large international GWAS. Currently the reported risk alleles do not sufficiently explain the phenotypic variance to be used for individual prediction of disease risk, disease course or response to medication. Future genetic research will provide important insights into the biological basis of BD by the identification of additional genes associated with BD. This knowledge of genetics will help identify potential etiological subgroups as well as cross-diagnostic disease mechanisms.
双相情感障碍(BD)具有多因素病因。其发病受遗传和环境因素影响。大型全基因组关联研究(GWAS)首次成功复制了该疾病的遗传风险等位基因变异,标志着在确定相关风险基因方面取得了突破。除了GWAS鉴定出的这些具有中等效应的常见遗传变异外,预计具有较高外显率的罕见变异也在疾病发展中发挥作用。近期研究结果表明,拷贝数变异可能对BD的发生有影响,尽管其程度低于精神分裂症或自闭症等其他精神疾病。最初的下一代测序研究结果显示,在先前发现与BD相关的通路和基因中,罕见变异有所富集。在药物遗传学领域,最近一项大型国际GWAS首次鉴定出一个影响锂治疗反应个体差异的风险基因。目前,所报道的风险等位基因尚不足以充分解释表型变异,无法用于个体疾病风险、病程或药物反应的预测。未来的基因研究将通过鉴定与BD相关的其他基因,为BD的生物学基础提供重要见解。这种遗传学知识将有助于识别潜在的病因亚组以及跨诊断疾病机制。