Bipolar Disorder 1 Genetics of bipolar disorder
Bipolar Disorder 1 Genetics of bipolar disorder
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DOI：
10.1016/s0140-6736(13)60855-7
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发表时间：
2013-05-11
期刊：
影响因子：
168.9
通讯作者：
Sklar, Pamela
中科院分区：
文献类型：
--
作者：
Craddock, Nick;Sklar, Pamela
对家庭和双胞胎的研究显示了影响双相情感障碍易感性的遗传因素的重要性，并提示了大量的遗传和表型复杂性。最近，在一些常见多态性的全基因组关联研究中，包括CACNA1C、ODZ4和NCAN基因的变异，报道了强大的、可复制的全基因组显著关联。有强有力的证据表明多基因对风险有贡献（即许多风险等位基因的影响很小）。一个值得注意的发现是双相情感障碍和精神分裂症在几个个体风险等位基因和多基因风险上的易感性重叠。相比之下，基因组结构变异在双相情感障碍中的作用似乎比在精神分裂症中的作用要小。总之，这些遗传发现为未来的研究指明了方向，以描述双相情感障碍的病因和发病机制，表明需要重新评估我们的诊断分类，并可能最终为临床管理的重大改进铺平道路。
Studies of families and twins show the importance of genetic factors affecting susceptibility to bipolar disorder and suggest substantial genetic and phenotypic complexity. Robust and replicable genome-wide significant associations have recently been reported in genome-wide association studies at several common polymorphisms, including variants within the genes CACNA1C, ODZ4, and NCAN. Strong evidence exists for a polygenic contribution to risk (ie, many risk alleles of small effect). A notable finding is the overlap of susceptibility between bipolar disorder and schizophrenia for several individual risk alleles and for the polygenic risk. By contrast, genomic structural variation seems to play a smaller part in bipolar disorder than it does in schizophrenia. Together, these genetic findings suggest directions for future studies to delineate the aetiology and pathogenesis of bipolar disorder, indicate the need to re-evaluate our diagnostic classifications, and might eventually pave the way for major improvements in clinical management.