Twin studies suggest that substance use initiation in children  and adolescents is determined primarily by environmental influences, whereas the  establishment of use patterns is strongly controlled by genetic factors. 
The  present study analysed the effects of the serotonin transporter promoter  polymorphism [5-HT transporter gene-linked polymorphic region (5-HTTLPR)] and  the α2A-adrenoceptor C-1291G genotype (ADRA2A C-1291G) as well  as their interaction effects on alcohol, tobacco and drug use from  preadolescence to the late adolescence.   
Initial sample of 9-year-old children of Estonian Children  Personality Behaviour and Health Study (n = 583) was recalled at ages 15  and 18. Participants reported in all waves how frequently they smoked and used  alcohol and illicit drugs. 
5-HTTLPR had age-dependent effects on alcohol, tobacco and  drug use: substance use did not differ by genotype at age 9, but at age 15, the  participants with the short (s)/s genotype had higher tobacco use, and at age  18, they were more active alcohol, drug and tobacco users. 
Effects of  ADRA2A C-1291G on drug use were dependent on gender, age and 5-HTTLPR.  Males (age 18) with ADRA2A CG genotype, when compared to other  participants, tended to have higher drug use especially when they had s/s  genotype of 5-HTTLPR. 
Our results reveal that expression of genetic vulnerability  for substance use in children and adolescents may depend on age, gender,  interaction of genes, and type of substance.
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