使用多因素易患性阈值模型评估双相情感障碍的遗传度缺失

doi:10.3724/SP.J.1005.2014.0897

遗传 ›› 2014, Vol. 36 ›› Issue (9): 897-902.doi: 10.3724/SP.J.1005.2014.0897

使用多因素易患性阈值模型评估双相情感障碍的遗传度缺失

李康^{1, 2}, 许瑞环³, 张洪德², 王前¹

1. 南方医科大学南方医院检验医学中心,广州 510515; 2. 深圳市龙岗中心医院中心实验室,深圳 518116; 3. 深圳市龙岗中心医院检验科,深圳 518116

收稿日期:2014-01-31 出版日期:2014-09-20 发布日期:2014-09-20
通讯作者: 王前,博士,教授,研究方向：复杂疾病的快速诊断。E-mail：wangqian@smu.edu.cn E-mail:kangerem@163.com
作者简介:李康,硕士,主管技师,研究方向：复杂疾病的基因组和蛋白质组学。
基金资助:
广东省科技厅课题项目(编号：2011B061200003)资助

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

Kang Li^{1, 2}, Ruihuan Xu³, Hongde Zhang², Qian Wang¹

1. Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 2. Central Laboratory, Longgang District Central Hospital, Shenzhen 518116, China; 3. Clinical Laboratory, Longgang District Central Hospital, Shenzhen 518116, China

Received:2014-01-31 Online:2014-09-20 Published:2014-09-20

摘要/Abstract

摘要： 为了评估双向情感障碍的遗传度缺失,文章通过查询美国国家人类基因组研究所(National Human Genome Research Institute,NHGRI)的gwascatalog目录,检索出所有已发现的双相情感障碍易感变异,使用多因素易患性阈值模型计算每个易感变异对双相情感障碍遗传度的解释度。将所有易感变异遗传度解释度求和得到双相情感障碍已知易感变异对遗传度的总解释度,使用此总解释度评估双相情感障碍的遗传度缺失。结果显示,已知双相情感障碍易感变异对双相情感障碍遗传度的合计解释度为38.34%,尚有61.66%的遗传度无法被已有易感变异解释,属于遗传度缺失。双相情感障碍38.34%的遗传度解释度较早前国外同类研究大幅度提高,表明随着新的双相情感障碍易感变异被不断发现,双相情感障碍遗传度缺失得到大幅度减小。但双相情感障碍遗传度缺失依然存在且数目较大的事实也表明双相情感障碍尚存在许多未知的分子遗传学机制有待进一步阐明。

关键词: 双相情感障碍, 遗传度, 遗传度缺失, 易患性阈值模型

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.

Key words: bipolar disorder, heritability, missing heritability, liability threshold model

李康, 许瑞环, 张洪德, 王前. 使用多因素易患性阈值模型评估双相情感障碍的遗传度缺失[J]. 遗传, 2014, 36(9): 897-902.

Kang Li, Ruihuan Xu, Hongde Zhang, Qian Wang. Evaluating the missing heritability of bipolar disorder using the multifactorial liability threshold model[J]. HEREDITAS(Beijing), 2014, 36(9): 897-902.

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使用多因素易患性阈值模型评估双相情感障碍的遗传度缺失

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

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