基于相关个体拷贝数变异数据的趋势检验及在孤独症数据中的应用  

Trend Tests Based on Copy Number Variations of Related Individuals and Application in Autism Data

作　　者：吕梦轩 王昱泉 胡跃清 LüMengxuan;WANG Yuquan;HU Yueqing(Department of Biostatistics and Computational Biology,School of Life Sciences,Fudan University,Shanghai 200433,China)

机构地区：[1]复旦大学生命科学学院生物统计学与计算生物学系,上海200433

出　　处：《复旦学报（自然科学版）》2020年第6期713-724,共12页Journal of Fudan University：Natural Science

基　　金：国家自然科学基金(11971117)。

摘　　要：拷贝数变异是人类基因组遗传多样性的重要组成部分,是当前的研究热点.然而相应的关联研究方法不多,尤其是个体有血缘关系时.本文基于相关个体,在Cochran-Armitage趋势检验的基础上,针对拷贝数变异数据是可基因分型和不可基因分型两种情形,推导出检验方法MTT.随机模拟结果表明:MTT方法具有良好的功效表现,适用范围更广.同时,本文比较了不同数据采集方案对MTT功效的影响,结果表明相关病例不相关对照具有较高的性价比.运用MTT分析孤独症真实数据,检测出与疾病显著相关的拷贝数变异位点和相关基因,基因功能富集分析和文献检索说明了结果的可靠性,这为后续研究提供了指引.As a main contributor to human genome diversity,Copy Number Variations(CNVs)have been a topic of great interest.However,existing methods for association study of human diseases with CNVs are not applicable to the related individuals.In this study,with the concern of the situation that CNVs could be categorized as genotypable and ungenotypable,we derived practicable forms of the test statistic MTT for related individuals based on Cochran-Armitage trend test.Simulation results indicated that our proposed test statistic MTT had more extensive applicability and could offer better powers.In addition,comparisons of the results from different data collection strategies showed that recruiting related cases and unrelated controls as subjects of study may work better.Besides,we applied the proposed test MTT into the real data analysis of autism and identified several CNV loci and related genes significantly associated with the disease.Functional analysis of these genes demonstrated their roles in autism,which also provides guidelines for further relevant studies.

关 键 词：拷贝数变异 趋势检验 相关个体 孤独症 群体数据 

分 类 号：Q348[生物学—遗传学]