Statistical issues and approaches in endophenotype research  

作　　者：SHAM Pak Chung CHERNY Stacey S HALL Mei-Hua 

机构地区：[1]Department of Psychiatry and The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China [2]Psychology Research Laboratory, McLean Hospital, Harvard Medical School, Boston, MA 02115-6092, USA

出　　处：《Chinese Science Bulletin》2011年第32期3403-3408,共6页

基　　金：supported by the Hong Kong Research Grants Council General Research Fund (HKU 766906M and HKU 774707M);the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (Project EU-GEI);the University of Hong Kong (HKU) Strategic Research Theme of Genomics, HKU Small Project Funding (201007176248);the National Institute of Mental Health of the USA (1K01MH086714)

摘　　要：The endophenotype concept was initially proposed to enhance the power of genetic studies of complex disorders. It is closely related to the genetic component in a liability-threshold model; a perfect endophenotype should have a correlation of 1 with the genetic component of the liability to disease. In reality, a putative endophenotype is unlikely to be a perfect representation of the genetic component of disease liability. The magnitude of the correlation between a putative endophenotype and the genetic component of disease liability can be estimated by fitting multivariate genetic models to twin data. A number of statistical methods have been developed for incorporating endophenotypes in genetic linkage and association analyses with the aim of improving statistical power. The most recent of such methods can handle multiple endophenotypes simultaneously for the greatest increase in power. In addition to increasing statistical power, endophenotype research plays an important role in helping to understand the mechanisms which connect the associated genetic variants with disease occurrence. Novel statistical approaches may be required for the analysis of the complex relationships between endophenotypes at different levels and how they converge to cause the occurrence of disease.The endophenotype concept was initially proposed to enhance the power of genetic studies of complex disorders. It is closely related to the genetic component in a liability-threshold model; a perfect endophenotype should have a correlation of 1 with the genetic component of the liability to disease. In reality, a putative endophenotype is unlikely to be a perfect representation of the genetic component of disease liability. The magnitude of the correlation between a putative endophenotype and the genetic com- ponent of disease liability can be estimated by fitting multivariate genetic models to twin data. A number of statistical methods have been developed for incorporating endophenotypes in genetic linkage and association analyses with the aim of improving statistical power. The most recent of such methods can handle multiple endophenotypes simultaneously for the greatest increase in power. In addition to increasing statistical power, endophenotype research plays an important role in helping to understand the mechanisms which connect the associated genetic variants with disease occurrence. Novel statistical approaches may be required for the analysis of the complex relationships between endophenotypes at different levels and how they converge to cause the oc- currence of disease.

关 键 词：统计问题 稳定 遗传疾病 COM组件 复杂疾病 组成部分 模型估计 统计方法 

分 类 号：R394[医药卫生—医学遗传学]