Using missing data methods in genetic studies with missing mutation status

作     者：Leong, T Lipsitz, SR Ibrahim, JG 

作者机构：Dana Farber Canc Inst Dept Biostat Sci Boston MA 02115 USA Harvard Univ Sch Publ Hlth Dept Biostat Boston MA 02115 USA 

出 版 物：《STATISTICS IN MEDICINE》 (医学统计学)

年 卷 期：1999年第18卷第4期

页      面：473-485页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 0714[理学-统计学（可授理学、经济学学位）] 10[医学] 

基　　金：NCI NIH HHS [CA70101  CA55576  CA74015] Funding Source: Medline 

主　　题：Genes ras Likelihood Functions Multiple Myeloma Mutation Codon 基因 RAS 似然函数 多发性骨髓瘤 突变 Codons Computer Programming Languages Mutation expectation-maximisation algorithm Likelihood Functions Multiple Myeloma missing data ras Oncogene Clinical Investigators outcome variable Odds Ratio 

摘      要：Because of current techniques of determining gene mutation, investigators are now interested in estimating the odds ratio between genetic status (mutation, no mutation) and an outcome variable such as disease cell type (A, B). In this paper we consider the mutation of the RAS genetic family. To determine if the genes have mutated, investigators look at five specific locations on the RAS gene. RAS mutated is a mutation in at least one of the five gene locations and RAS non-mutated is no mutation in any of the five locations. Owing to limited time and financial resources, one cannot obtain a complete genetic evaluation of all five locations on the gene for all patients. We propose the use of maximum likelihood (ML) with a 2(6) multinomial distribution formed by cross-classifying the binary mutation status at five locations by binary disease cell type. This ML method includes all patients regardless of completeness of data, treats the locations not evaluated as missing data, and uses the EM algorithm to estimate the odds ratio between genetic mutation status and the disease type. We compare the ML method to complete case estimates, and a method used by clinical investigators, which excludes patients with data on less than five locations who have no mutations on these sites. Copyright (C) 1999 John Wiley & Sons, Ltd.