RESEARCH REPORT © 2004 Society for the Study of Addiction doi:10.1111/j.1360-0443.2004.00877.x Addiction, 99, 1403–1409 Blackwell Science, LtdOxford, UKADDAddiction0965-2140© 2004 Society for the Study of Addiction 99 Original Article Development of alcoholic symptoms in male twins I-Chao Liu et al. Correspondence to: I-Chao Liu Department of Psychiatry Cardinal Tien Hospital no. 5 Alley 20 Ln. 790 Chung-hsiao E. Road Sec. 5 Taipei Taiwan 110 Fax: 011 886 2 27262825 E-mail: iliu@post.harvard.edu Submitted 17 April 2003; initial review completed 29 July 2003; final version accepted 22 June 2004 RESEARCH REPORT Genetic and environmental contributions to age of onset of alcohol dependence symptoms in male twins I-Chao Liu 1 , Deborah L. Blacker 2,4 , Ronghui Xu 3 , Garrett Fitzmaurice 3 , Ming T. Tsuang 2,4 & Michael J. Lyons 5 Department of Psychiatry, Cardinal Tien Hospital, Taipei, Taiwan, 1 Departments of Epidemiology 2 and Biostatistics 3 , Harvard School of Public Health, Boston, MA, Department of Psychiatry, Harvard Medical School, Boston, MA 4 and Department of Psychology, Boston University, Boston, MA, USA 5 ABSTRACT Aims To investigate genetic and environmental influences on the develop- ment of specific alcohol dependence symptoms. Design and participants A classical twin study of 3372 male–male twin pairs in the Vietnam Era Twin (VET) Registry based on telephone interviews about alcohol use. Measurements The nine diagnostic symptoms according to the Diagnostic and Statistical Manual of Mental Disorder, version III (revised) (DSM-III-R) definition of alcohol dependence. Symptoms were grouped into those based on impaired control, biological effects and social consequences (Beresford’s classification) or early versus late symptoms (Nelson’s classification). Survival models with ran- dom effects were used to examine the age of onset of each symptom. Findings Approximately 38% of the variation in age of onset of each symptom group based on Beresford’s classification is due to additive genetic factors. The age of onset of late symptoms from Nelson’s classification appears to be most affected by genetic factors. Estimates of genetic effects for impaired control symptoms are greatly decreased when twins with comorbid psychiatric disor- ders are excluded. Conclusions Our results support the heritability of age of onset of DSM-III-R- defined symptoms for alcohol dependence. However, no symptom group in Beresford’s classification could be identified as more heritable than other symp- tom groups. A strong association between genetic vulnerability and co- occurring diseases for symptoms indicative of impaired control could be found. In addition, our findings show that the late symptom group could be a good can- didate for subsequent genetic research. KEYWORDS Alcohol dependence, random effects, survival model, twin studies. INTRODUCTION More than one-tenth of the general population has been found to meet a life-time diagnosis of alcohol abuse or dependence in population-based surveys [1,2]. Through twin and adoption studies, a heritable basis for alcohol dependence has been confirmed, particularly in men [3,4]. However, studies focusing on the appearance of alcohol dependence alone do not provide sufficient infor- mation about determinants along the developmental course. To fulfill this need, we require the knowledge of genetic and environmental effects on determining when and how quickly this disorder develops. Twin studies con- centrating on this issue would guide us in an appropriate direction to identify risk factors at different stages of development.