PDF(Pubmed)
Abstract：
Psychiatric disorders such as bipolar disorder and schizophrenia are highly heritable. While the genetic contribution to psychiatric disorders is quite sure, specific genetic factors contributing to particular conditions have long been a mystery. Empowered by the initial report of the Human Genome Project, the analysis of the comprehensive set of the human genome, called \"genomics,\" became possible. Subsequent development of large-scale genomic technologies enabled us to elucidate various disease-related genetic information, accelerating our understanding of various diseases. Genomic research on psychiatric disorders is not an exception. In this Review, I introduce significant advancements in psychiatric genomics with a special focus on our investigation of bipolar disorder. International consortiums and advocacy groups accelerate psychiatric genomics, increasing the sample size and statistical power for robust findings. The genetic architecture of schizophrenia has been elucidated in both common and rare variant studies. The genetic architecture of autism spectrum disorder (ASD) has been elucidated mainly by rare variant analysis. As to bipolar disorder, common variant analysis precedes rare variant analysis, but we are struggling to elucidate relevant rare variants. While the genomic approach has explained specific genetic factors for particular disorders, overlapping risk genes or pleiotropy has been observed more than expected. The boundary in the current nosology of psychiatric disorders is more or less challenged. To understand the genotype-phenotype relation more deeply, an attempt to understand phenotypes based on genotypes, called the \"genotype first\" approach, has started. I discuss this new approach for better understanding and treatment of psychiatric disorders.
摘要：
精神紊乱如躁郁症和精神分裂症是高度遗传性的。虽然基因对精神疾病的贡献是相当肯定的，导致特定条件的特定遗传因素长期以来一直是个谜。人类基因组计划的初步报告授权，对人类基因组的全面分析，叫做“基因组学，“成为可能。随后大规模基因组技术的发展使我们能够阐明各种疾病相关的遗传信息，加快我们对各种疾病的了解。关于精神疾病的基因组研究也不例外。在这篇评论中,我介绍了精神病学基因组学的重大进展，特别关注我们对躁郁症的研究。国际财团和倡导团体加速精神病学基因组学，增加样本量和统计能力，以获得稳健的发现。精神分裂症的遗传结构已在常见和罕见的变异研究中得到阐明。自闭症谱系障碍（ASD）的遗传结构主要通过罕见的变异分析得到阐明。至于双相情感障碍，常见变异分析先于罕见变异分析，但是我们正在努力阐明相关的罕见变体。虽然基因组方法已经解释了特定疾病的特定遗传因素，重叠的风险基因或多效性比预期的要多。当前精神疾病的疾病学边界或多或少受到了挑战。为了更深入地理解基因型与表型的关系，试图理解基于基因型的表型，称为“基因型优先”方法，已经开始。我将讨论这种新方法，以更好地理解和治疗精神疾病。
