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Behav Genet. 2006 Jul;36(4):507-24. Epub 2006 Jun 8.

Extensions to the modeling of initiation and progression: applications to substance use and abuse.

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Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 980126, Richmond, VA, 23298-0126, USA.


Twin data can provide valuable insight into the relationship between the stages of phenomena such as disease or substance abuse. Initiation of substance use may be caused by factors that are the same as, partially shared with, or completely independent of those that cause progression from use to abuse. Comparison of rates of progression among the cotwins of twins who do vs. do not initiate provides indirect information about the relationship between initiation and progression. Existing models for this relationship have been difficult to extend because they are usually expressed in terms of explicit integrals. In this paper, the problem is overcome by regarding the analysis of twin data on initiation and progression as a special case of missing data, in which individuals who do not initiate are regarded as having missing data on progression measures. Using the general framework for the analysis of ordinal data with missing values available in Mx makes extensions that include other variables much easier. The effects of continuous covariates such as age on initiation and progression becomes simple. Also facilitated are the examination of initiation and progression in two or more substances, and transition models with two or more steps. The methods are illustrated with data on the effects of cohort on liability to cannabis use and abuse, bivariate analysis of tobacco use and dependence and cannabis use and abuse, and the relationships between initiation of smoking, regular smoking and nicotine dependence. Other suitable applications include the relationship between symptoms and diagnosis, such as fears and the progression to phobia.

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