Association of <i>TMEM106B</i> Gene rs1990622 Polymorphism with Cognitive Impairment in Adolescents with Depressive Disorder

Genetic variations may serve as a critical factor in depressive cognitive impairment development. The study aimed to investigate the association between the TMEM106B gene rs1990622 polymorphism and cognitive impairment in individuals with depression. A total of 700 participants were enrolled in this study, comprising 350 adolescent depression patients without cognitive impairment (control group) and 350 adolescent depression patients with cognitive impairment (cognitive impairment group). Depressive symptom severity was evaluated with the Hamilton Depression Rating Scale (HAMD-17), and cognitive dysfunction was screened using the Montreal Cognitive Assessment-Beijing version (MoCA-BJ). Genotyping of TMEM106B rs1990622 was performed using the Sanger sequencing method, while the expression of TMEM106B was measured by RT-qPCR. Logistic regression identified risk factors for cognitive impairment in adolescent depression. Individuals carrying the GA (P = 0.014, OR = 1.568, 95% CI:1.093-2.251) and AA (P < 0.001, OR = 2.455, 95% CI:1.630-3.699) genotype at the TMEM106B rs1990622 locus exhibited an increased risk of cognitive impairment, suggesting that the A allele may serve as a risk factor for cognitive impairment in this population (P < 0.001, OR = 1.629, 95% CI:1.319-2.012). Depression patients with the AA genotype demonstrated the poorest cognitive performance. Furthermore, the expression level of the TMEM106B gene was significantly higher in the cognitive impairment group. Educational attainment, the GA and AA genotypes at rs1990622, and TMEM106B expression levels were identified as independent risk factors for depressive cognitive impairment. The TMEM106B rs1990622 variant may significantly impact cognitive impairment in depression patients.