Associations of BDNF and NTRK2 Polymorphisms with ADHD in Children with Prenatal Alcohol Exposure

Background/Objectives: Brain-derived neurotrophic factor (BDNF) and its receptor TrkB, encoded by NTRK2, are involved in neurodevelopment and may contribute to variability in outcomes following prenatal alcohol exposure. We investigated whether BDNF rs6265, BDNF rs56164415, and NTRK2 rs10868235 were associated with attention-deficit/hyperactivity disorder (ADHD) in children with confirmed high prenatal alcohol exposure (hPAE), and whether these associations differed across fetal alcohol spectrum disorder (FASD) phenotype groups. Methods: The study included 270 children aged 4–17 years with hPAE, comprising 111 with previously established clinical ADHD diagnoses and 159 without ADHD. Participants were classified as having fetal alcohol syndrome (FAS), partial FAS (pFAS), or a non-FAS phenotype. Genotyping was performed using TaqMan real-time PCR assays. Additive genetic associations were evaluated using logistic regression adjusted for sex, FASD phenotype, and age modeled with natural cubic splines. Exploratory genotype-by-FASD phenotype interactions were assessed, with Holm correction for multiple comparisons. Results: No statistically significant associations were identified in the adjusted additive models: NTRK2 rs10868235, per C allele (OR = 0.91, 95% CI: 0.63–1.31; p = 0.619); BDNF rs56164415, per T allele (OR = 1.20, 95% CI: 0.48–2.99; p = 0.701); and BDNF rs6265, per A allele (OR = 1.29, 95% CI: 0.79–2.09; p = 0.308). No statistically significant global genotype-by-FASD phenotype interactions were identified. In the pFAS subgroup (n = 37), the NTRK2 rs10868235 C allele showed a nominal association with lower odds of ADHD (OR = 0.25, 95% CI: 0.07–0.92; p = 0.038), which did not remain significant after Holm correction (adjusted p = 0.114). Conclusions: No statistically significant associations between the investigated variants and ADHD were identified in this hPAE cohort. Limited statistical precision precludes excluding modest genetic effects. The exploratory pFAS finding is compatible with chance and does not establish a phenotype-specific genetic association. Because all participants had hPAE, genotype-by-prenatal alcohol exposure interactions could not be assessed.