Study 21 – Twin Family Study of Vulnerability to Substance Abuse

Investigator:  William G. Iacono

Release Date:  Combined with NIDA Study 25

Abstract:  Our study seeks to identify genetic and environmental influences on the development of substance abuse. It uses a prospective cohort research design to follow twins longitudinally from childhood, through adolescence and into early adulthood. This design allows us to identify initial experimentation; persistence of licit and illicit substances; and desistance of substance use. The study has a comprehensive set of psychological, environmental and psychophysiological assessments. As part of an administrative supplement, we are adding a molecular genetic assessment with the following specific aims:

First, we propose to add all of the willing participants in this project to the NIDA Genetics Consortium data base. We have 666 participating male twin pairs, (1332 individuals) plus 1314 of their biological parents available for inclusion in the NGC data base.

Second, we propose to initially study selected key candidate genes that have been linked to the spectrum of DSM disorders associated with the development of substance use disorders. As additional candidate genes are identified, we hope to be able to include them as appropriate. We expect to be able to take advantage of the parent data to use family-based association methods (e.g., TDT) as well as genomic control methods.

Third, we also propose to study the association between these candidate genes and well-defined alternative phenotypes (or endophenotypes) that we have measured. These include P300 amplitude, spontaneous EEG, and other measures related to eye tracking and working memory. We have already carried out a preliminary study on a subset of participants examining the association of COMT with these measures, and found, as hypothesized, that those homozygous for the met allele performed working memory and antisaccade eye tracking tasks better than those homozygous for the val allele.


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