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Introduction: Brain-derived neurotrophic factor (BDNF) is a growth factor in the central nervous system. There is evidence for the involvement of BDNF in addictions and mental disorders. We aimed to replicate the earlier reported association of a functional genetic variant of BDNF with smoking initiation (SI) using a large population-based sample and to test whether the association is independent of depression.Methods: Our sample was drawn from the Finnish population-based FINRISK surveys conducted in 1992, 1997, 2002, and 2007. We had nonmissing data on the genotype BDNF  Val66Met (G/A) variant (rs6265) and self-reported never (n = 10 619) versus ever (n = 16 028) smoking among 26 647 adults aged 25-74 years. The association between BDNF  Val66Met and SI was modeled using logistic regression adjusted for age and sex, and in secondary analyses also for depression. Depression was defined as self-reported depression diagnosed or treated by physician during the past year.Results: The sex- and age-adjusted analysis confirmed that the major (Val) allele increased the risk of being a lifetime ever smoker (per allele odds ratio [OR] = 1.07; 95% CI = 1.01 to 1.12; p = .01). When depression, which itself was significantly associated with SI (OR = 1.58; 95% CI = 1.37 to 1.82; p < .001), was added to the model, the association of the gene with SI remained significant (per allele OR = 1.06; 95% CI = 1.01 to 1.12; p = .01). Exclusion of depressed individuals did not change the results (OR = 1.06; 95% CI = 1.01 to 1.12; p = .02).Conclusions: In a Finnish population sample, we replicated the earlier reported association of BDNF Val66Met with SI. Our data further suggest that this association is independent of depression.Implications: Earlier finding about the association between the BDNF gene and smoking initiation is replicated and shown to be independent of depression within Finnish adult population. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to analyze associations of dopamine receptor genes (DRD1-5) with Major Depressive Disorder (MDD) and nicotine dependence (ND), and to investigate whether ND moderates genetic influences on MDD. Methods: The sample was ascertained from the Finnish Twin Cohort. Twin pairs concordant for smoking history were recruited along with their family members, as part of the multisite Nicotine Addiction Genetics consortium. Genetic association analyses were based on 1428 adults. Total of 70 tagging single nucleotide polymorphisms within the dopamine receptor genes were genotyped and analyzed for association with MDD, ND, and MD-ND co-morbidity. Individual level logistic regression analyses were based on 1296 adults with data on ND and MDD diagnoses, as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use. Four independent samples, such as population-based and case-control samples, were used for replication. Results: Rs2399496, located 1.5 kb downstream of DRD3, showed suggestive association for MDD (p = 0.00076) and significant association for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND-interaction justified analyses by genetic risk variant and ND status. Individuals with ND and two minor alleles (AA) of rs2399496 had almost six-fold risk for MDD (OR 5.74, 95%CI 3.12–10.5, p = 9.010e-09) compared to individuals without ND and with two major alleles (TT). Conclusions: Significant association between a variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our results further suggest that nicotine dependence may potentiate the influence of the DRD3 genetic variant on MDD. [ABSTRACT FROM AUTHOR]