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[使用多因素易感性阈值模型评估双相情感障碍的缺失遗传率]

[Evaluating the missing heritability of bipolar disorder using the multifactorial liability threshold model].

作者信息

Li Kang, Xu Ruihuan, Zhang Hongde, Wang Qian

机构信息

Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Central Laboratory, Longgang District Central Hospital, Shenzhen 518116, China;

Clinical Laboratory, Longgang District Central Hospital, Shenzhen 518116, China.

出版信息

Yi Chuan. 2014 Sep;36(9):897-902. doi: 10.3724/SP.J.1005.2014.0897.

Abstract

In order to evaluate the missing heritability of bipolar disorder, we queried the GWAS catalog of National Human Genome Research Institute, retrieve all the susceptible gene variation of bipolar disorder, and calculate the heritability explanation degree of each susceptibility variant using the multifactorial liability threshold model. The total heritability explanation degree of bipolar disorder was obtained through summing up the heritability explanation degree of each susceptibility variant. Then, we evaluated the missing heritability of bipolar disorder based on the total heritability explanation degree. The results showed that the total heritability explanation degree of bipolar disorder explained by known susceptible variants was 38.34%, and the other 61.66% of heritability can't be explained by known susceptibility variants, which belong to the missing heritability of bipolar disorder. The total heritability explanation degree of bipolar disorder in this study was significantly increased compared to earlier similar studies abroad. With constant discovery of new bipolar disorder susceptibility variants, the missing heritability of bipolar disorder has been greatly reduced, but the missing heritability of bipolar disorder still exists and occupies a large part of the bipolar disorder heritability, indicating that the molecular genetic mechanisms of bipolar disorder need to be further clarified.

摘要

为了评估双相情感障碍的遗传度缺失情况,我们查询了美国国立人类基因组研究所的全基因组关联研究(GWAS)目录,检索了双相情感障碍的所有易感基因变异,并使用多因素遗传阈值模型计算每个易感变异的遗传度解释程度。通过汇总每个易感变异的遗传度解释程度,得到双相情感障碍的总遗传度解释程度。然后,我们基于总遗传度解释程度评估双相情感障碍的遗传度缺失情况。结果显示,已知易感变异解释的双相情感障碍总遗传度解释程度为38.34%,另外61.66%的遗传度无法由已知易感变异解释,这部分属于双相情感障碍的遗传度缺失。与国外早期类似研究相比,本研究中双相情感障碍的总遗传度解释程度显著提高。随着双相情感障碍新易感变异的不断发现,双相情感障碍的遗传度缺失已大幅减少,但双相情感障碍的遗传度缺失仍然存在,且在双相情感障碍遗传度中占很大一部分,这表明双相情感障碍的分子遗传机制仍需进一步阐明。

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