In genetic studies of complex diseases, particularly mental illnesses, and behavior disorders, two distinct characteristics have emerged in some data sets. First, genetic data sets are collected with a large number of...In genetic studies of complex diseases, particularly mental illnesses, and behavior disorders, two distinct characteristics have emerged in some data sets. First, genetic data sets are collected with a large number of phenotypes that are potentially related to the complex disease under study. Second, each phenotype is collected from the same subject repeatedly over time. In this study, we present a nonparametric regression approach to study multivariate and time-repeated phenotypes together by using the technique of the multivariate adaptive regression splines for analysis of longitudinal data (MASAL), which makes it possible to identify genes, gene-gene and gene-environment, including time, interactions associated with the phenotypes of interest. Furthermore, we propose a permutation test to assess the associations between the phenotypes and selected markers. Through simulation, we demonstrate that our proposed approach has advantages over the existing methods that examine each longitudinal phenotype separately or analyze the summarized values of phenotypes by compressing them into one-time-point phenotypes. Application of the proposed method to the Framingham Heart Study illustrates that the use of multivariate longitudinal phenotypes enhanced the significance of the association test.展开更多
Ovarian cancer is one of the most deadly female genital malignant tumors in many regions while an effective early screening strategy can save numerous lives.CA125 and HE4 are tumor markers validated efficacious as wel...Ovarian cancer is one of the most deadly female genital malignant tumors in many regions while an effective early screening strategy can save numerous lives.CA125 and HE4 are tumor markers validated efficacious as well as most commonly used in recent screening research of ovarian cancer.In this paper,the authors construct a change-point and mixture model on the basis of longitudinal CA125 and HE4 levels and estimated parameters using maximum likelihood method with the preclinical duration assumed right-censored,which is more adaptive and yields comparable results in comparison to the Bayesian approach raised by Skates.Consistency of estimators is proved.The authors also run a 5-year simulation of sequential screening by calculating the risk of cancer and hypothesis testing the true incidence time respectively.Results show that diagnosis based on hypothesis test performs better in early detection.展开更多
基金The authors thank two anonymous referees for their constructive comments and suggestions. This work was supported by grant R01 DA016750-09 from the National Institute on Drug Abuse. Zhu's work was also supported by the National Natural Science Foundation of China (Grant No. 11001044), the Yhndamental Research ~nds for the Central Universities (11CXPY007, 10JCXK001), the Natural Science Foundation of Jilin Province (Grant No. 201215007), the Scientific Research Foundation for Returned Scholars, MOE of China, and the Program for Changjiang Scholars and Innovative Research Team in University. The Framingham Heart Study project is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (N01 HC25195). The Framingham data used for the analyses described in this manuscript were obtained through dbGaP (phs000128.v3.p3).
文摘In genetic studies of complex diseases, particularly mental illnesses, and behavior disorders, two distinct characteristics have emerged in some data sets. First, genetic data sets are collected with a large number of phenotypes that are potentially related to the complex disease under study. Second, each phenotype is collected from the same subject repeatedly over time. In this study, we present a nonparametric regression approach to study multivariate and time-repeated phenotypes together by using the technique of the multivariate adaptive regression splines for analysis of longitudinal data (MASAL), which makes it possible to identify genes, gene-gene and gene-environment, including time, interactions associated with the phenotypes of interest. Furthermore, we propose a permutation test to assess the associations between the phenotypes and selected markers. Through simulation, we demonstrate that our proposed approach has advantages over the existing methods that examine each longitudinal phenotype separately or analyze the summarized values of phenotypes by compressing them into one-time-point phenotypes. Application of the proposed method to the Framingham Heart Study illustrates that the use of multivariate longitudinal phenotypes enhanced the significance of the association test.
基金supported by the Ph.D. Programs Foundation of Ministry of Education of China under Grant No.20090001110005the National Natural Science Foundation of China under Grant No.11171007
文摘Ovarian cancer is one of the most deadly female genital malignant tumors in many regions while an effective early screening strategy can save numerous lives.CA125 and HE4 are tumor markers validated efficacious as well as most commonly used in recent screening research of ovarian cancer.In this paper,the authors construct a change-point and mixture model on the basis of longitudinal CA125 and HE4 levels and estimated parameters using maximum likelihood method with the preclinical duration assumed right-censored,which is more adaptive and yields comparable results in comparison to the Bayesian approach raised by Skates.Consistency of estimators is proved.The authors also run a 5-year simulation of sequential screening by calculating the risk of cancer and hypothesis testing the true incidence time respectively.Results show that diagnosis based on hypothesis test performs better in early detection.