As evident from the publication of NIH Guide PA-02-112 """"""""Genetic Epidemiology of Substance Use Disorders,"""""""" substance use disorders (SUDs) pose serious public health and societal problems. Gene-gene and gene-environment interactions are potentially important factors in understanding the genetic epidemiology of SUDs. Advanced data analysis and modeling techniques become indispensable in this endeavor. Analytic advancement is generally regarded as one of the greatest challenges in genetic dissection of complex disease. To address this need, NIH Guide PA-02-112 encourages development of statistical tools and analytic methods to enhance our understanding of complex phenotypes including SUDs. This application response to this specific programmatic need by developing statistical methods that is useful for unraveling the genetic basis of complex disorders. Specifically, our primary aim is to develop, evaluate, and apply new statistical models (e.g., latent variable models and tree-based models), methods, and software to conduct genetic analyses of complex traits. We are particularly interested in ordinal traits because methods and software virtually do not exist. Once the methodologies are established, companion software will be developed for all of these models and made available to the public on Dr. Zhang's website. While the methodologies are being developed, as Dr. Zhang's group has demonstrated in the past, we will apply them to real data to address important public health problems, for example, those pertinent to the objectives of NIH Guide PA-02-112. We include three databases, which will allow us to study a variety of issues. For example, we will examine the potential sex difference in familial transmission of drug use and alcoholism, and identify candidate genes, gene-gene and gene-environment interactions for nicotine dependence. In our analyses, we will consider multiple phenotypes including alcohol, drug, and tobacco use as well as comorbid psychiatric conditions such as anxiety. Although the focus of application is on genetic epidemiology of SUBs, our methodologies will be useful for understanding complex ordinal traits in general.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA016750-04
Application #
7216951
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Weinberg, Naimah Z
Project Start
2004-04-15
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
4
Fiscal Year
2007
Total Cost
$179,195
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Pan, Wenliang; Tian, Yuan; Wang, Xueqin et al. (2018) BALL DIVERGENCE: NONPARAMETRIC TWO SAMPLE TEST. Ann Stat 46:1109-1137
You, Na; He, Shun; Wang, Xueqin et al. (2018) Subtype classification and heterogeneous prognosis model construction in precision medicine. Biometrics 74:814-822
Liu, Dungang; Zhang, Heping (2018) Residuals and Diagnostics for Ordinal Regression Models: A Surrogate Approach. J Am Stat Assoc 113:845-854
Guo, Xiaobo; Zhu, Junxian; Fan, Qiao et al. (2018) A univariate perspective of multivariate genome-wide association analysis. Genet Epidemiol 42:470-479
Wen, Canhong; Mehta, Chintan M; Tan, Haizhu et al. (2018) Whole genome association study of brain-wide imaging phenotypes: A study of the ping cohort. Genet Epidemiol 42:265-275
Mehta, Chintan M; Gruen, Jeffrey R; Zhang, Heping (2017) A method for integrating neuroimaging into genetic models of learning performance. Genet Epidemiol 41:4-17
Xiao, Feifei; Niu, Yue; Hao, Ning et al. (2017) modSaRa: a computationally efficient R package for CNV identification. Bioinformatics 33:2384-2385
Bi, Xuan; Yang, Liuqing; Li, Tengfei et al. (2017) Genome-wide mediation analysis of psychiatric and cognitive traits through imaging phenotypes. Hum Brain Mapp 38:4088-4097
Song, Chi; Min, Xiaoyi; Zhang, Heping (2016) THE SCREENING AND RANKING ALGORITHM FOR CHANGE-POINTS DETECTION IN MULTIPLE SAMPLES. Ann Appl Stat 10:2102-2129
Cao, Taoyun; Wang, Xueqin; Zhang, Heping (2016) Energy bagging tree. Stat Interface 9:171-181

Showing the most recent 10 out of 94 publications