Twin Research and Human Genetics


Genes, Environments, and Developmental Research: Methods for a Multi-Site Study of Early Substance Abuse

E. Jane Costelloa1 c1 *, Lindon Eavesa2, Patrick Sullivana3, Martin Kennedya4, Kevin Conwaya5, Daniel E. Adkinsa6, A. Angolda1, Shaunna L. Clarka6, Alaattin Erkanlia1, Joseph L. McClaya6, William Copelanda1, Hermine H. Maesa2, Youfang Liua7, Ashwin A. Patkara1, Judy Silberga2 and Edwin van den Oorda2

a1 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

a2 Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

a3 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

a4 Department of Pathology, University of Otago, North Dunedin, New Zealand

a5 Division of Epidemiology, Services and Prevention Research, National Institute on Drug Abuse, Bethesda, MD, USA

a6 Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA

a7 Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA


The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene–environment–development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene–environment analyses, of alcohol misuse and stressful life events, some significant gene–environment and gene–development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene–environment and gene–development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.

(Received August 17 2012)

(Accepted October 08 2012)


  • genomewide association study;
  • environment;
  • development;
  • multi-site


c1 Address for correspondence: Professor E. J. Costello, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Suite 22, Brightleaf Square, 905 West Main Street, Durham, NC 27701, USA. E-mail:


*  Authors are listed in the following order: The lead investigators at the study sites, followed by the rest of the research team in alphabetical order.