Genetic Epidemiology and Aging Research: Current Projects

Biometric and Measured Genetic Research on Smoking

Principal Investigator: Gary E. Swan, Ph.D., Director, Center for Health Sciences, SRI International

Co-Investigators: Janet Brigham, Ph.D., Senior Research Psychologist, SRI International, and Christina N. Lessov-Schlaggar, Ph.D., Genetic Epidemiologist, SRI International

It is widely accepted that nicotine is a highly addictive substance and that dependence on nicotine is largely responsible for persistent use of tobacco. There is growing recognition that nicotine dependence (ND) is a multidimensional construct, however, most studies continue to assess ND using the Fagerström Test for Nicotine Dependence (FTND), a 6-item self-administered paper-pencil measure or a diagnostic structured interview. The FTND has been criticized for its unidimensionality while the psychiatric interview is time consuming and expensive to administer. The current project aims to develop a psychometrically sound tobacco use instrument, the Lifetime Tobacco Use Questionnaire (LTUQ) that captures the multidimensionality of ND and is easy and inexpensive to administer.

Thus, Phase 1 of this project takes a measurement approach to ND and potential features, and applies psychometric principles to construct the LTUQ. An important feature of this strategy is the recognition that ND is a collection of phenotypes that range from simple static features (e.g., number of cigarettes smoked per day) to more complex dynamic features that change over time (e.g., time from first experimentation to regular use).

Phase 2 confronts the nature and extent of dimensionality of ND by applying confirmatory factor analysis to item sets from existing scales, those under development by other project teams including our own, and in consultation with a group of experts. Phenotypes that pass through the measurement filters of Phases 1 and 2 will be examined for heritability using the twin model in Phase 3.

Those that are determined to be heritable (and, by definition, can be assessed reliably and validly, and occupy a known location within a stable mutidimensional space) then will be recommended to measured genetic investigations for use in efforts seeking to establish genotype-phenotype associations of importance to ND.

Heritable and Social-Environment Risks for Substance Use

Project 1 of the Pacific Rim Transdisciplinary Tobacco & Alcohol Use Research Center

Project Principal Investigator and Center Co-Principal Investigator: Jennifer B. Unger, Ph.D., Assistant Professor, Keck School of Medicine, University of Southern California

Project Co-Investigator: Christina N. Lessov-Schlaggar, Ph.D., Genetic Epidemiologist, SRI International

Center Principal Investigator: C. Anderson Johnson, Ph.D., Director, Institute for Health Promotion & Disease Prevention Research & Division of Health Behavior Research, Keck School of Medicine, University of Southern California

Research in psychology, public health, and sociology has identified personality characteristics (e.g., depression, hostility, sensation-seeking) and characteristics of the social environment (e.g., peer and family influences, socioeconomic factors, stressful life events) as predictors of adolescent use of tobacco, alcohol, and other drugs. However, psychosocial research typically has not considered biological and genetic risk and protective factors as possible sources of resilience to substance use.  

Simultaneously, behavioral geneticists have investigated the etiology of substance use behavior by partitioning its phenotypic variance into genetic and environmental components, including shared and nonshared environments. Unfortunately, much of this research has been limited by imprecise measures of environmental risk and protective factors.

This study bridges the disciplines of psychology, sociology, public health, and behavioral genetics by using the methods of multiple disciplines to evaluate a model of adolescent tobacco and alcohol use etiology. We are collecting detailed data about tobacco and alcohol use, social-environmental factors, and personality characteristics among 600 pairs of adolescent twins in Southern California and 600 pairs of adolescent twins in Qingdao, China.  

This study distinguishes environmental risk and protective factors from heritable factors and identifies the specific aspects of the shared and nonshared environments that are associated with substance use. This study also assesses interactions between heritable factors and the social environment in the prediction of adolescent tobacco and alcohol use, to determine whether heritable characteristics make some adolescents more susceptible or resilient to risk factors in the social environment.

Genetic and Environmenal Causes of Variation in Cognition and Covariation with Brain Morphology and Midlife Risk Factors

Investigator: Christina N. Lessov-Schlaggar, Ph.D., Genetic Epidemiologist, SRI International

Primary Collaborators: Gary E. Swan, Ph.D., Director, Center for Health Sciences, SRI International and Dorit Carmelli, Ph.D., Senior Biostatistician and Epidemiologist, SRI International

This work uses data from participants of two studies of cardiovascular disease risk factors cohorts that have been followed for almost four decades, the Western Collaborative Group Study (WCGS) and the NHLBI Twin Study. The WCGS comprises of non-twin women and men and assessments include lifestyle questionnaires and interviews, laboratory physiological examinations, neuropsychological testing, genetic testing, and morbidity and mortality follow-up. The NHLBI study comprises of WWII veteran male twins who have been assessed using self-report questionnaire surveys, laboratory physiological examinations, neuropsychological testing, neurological testing, morphologic magnetic resonance imaging scanning, genetic testing, and morbidity and mortality follow-up.

Our current focus of interest is on:

• The behavioral and genetic determinants of pathologic changes in brain morphology, such as white matter disease and ventricular enlargement
• The behavioral and genetic determinants of neuropsychological performance, decline in performance, and association of performance with changes in brain morphology
• The behavioral and genetic determinants of covariation between midlife risk factors and later life neuropsychological performance and brain morphology
• The determination of neuroepidemiologic risk factors for mortality in older adults

Contact Us

For more information contact Gary Swan, director of the Center for Health Sciences.