Comorbid habitual smoking and alcohol dependence: A genomic survey

Objective: Habitual smoking and alcohol dependence are frequently comorbid, and evidence from twin studies demonstrates shared genetic factors are involved in the development of both disorders. Our objective is to locate genetic loci linked to both habitual smoking and alcohol dependence. Methods: Subjects were part of the Collaborative Study on the Genetics of Alcoholism (COGA). Individuals who met criteria for both DSM-IIIR alcohol dependence and Feighner definite alcoholism were identified in substance abuse treatment settings, and their relatives were recruited as a sample at high risk for substance dependence. All subjects were interviewed using a semistructured interview (SSAGA) that evaluated alcohol dependence, habitual smoking, and other psychiatric disorders. A genomic screen for genetic loci associated with both habitual smoking and alcohol dependence was performed on 64 families using 296 markers, and data were analyzed using nonparametric multipoint analyses (ASPEX). Results: There was significant familial aggregation of both habitual smoking and alcohol dependence, and there was evidence of cross-transmission. Relatives of alcohol- dependent probands were at increased risk of developing habitual smoking after controlling for the development of alcohol dependence. Genomic surveys of alcohol dependence and habitual smoking were performed independently, and this was compared to a genomic survey of the comorbid phenotype-alcohol dependence and habitual smoking. There was a maximum lod score of 2.9 on chromosome 2 using the combined phenotype (1.9 lod score alcohol dependence only and 0.6 lod score habitual smoking only). Conclusions: There is evidence of a shared genetic factor in the development of habitual smoking and alcohol dependence on chromosome 2.