Abstract: Depression is among the top five leading causes of disability and disease burden throughout the world. It is well established that depression often has its origins in childhood, and early adolescence is associated with a sharp increase in the prevalence. The mechanism underlying depression has been studied intensively during the last few decades. With the advancement of molecular genetics, a number of studies have been conducted in recent years to identify the candidate genes and investigate the gene-environment interactions related to depression. However, the extant research has mainly focused on serotoninergic and dopaminergic systems, muscarinic–cholinergic pathways have scarcely been investigated.
Although several recent studies have investigated the association between the polymorphisms in the CHRM2 gene and depression, the findings have not been always consistent. Meanwhile, no research on the effect of interaction between CHRM2 polymorphism and environment was reported. Besides, whether there is a moderating effect of age on the association between CHRM2 polymorphism and depression remains to be examined. The present study aimed to examine the association between rs1824024 polymorphism in the CHRM2 gene and depression among Chinese early adolescents, with particular focus on the moderating effect of negative life events, gender and grade on the association.
The subjects of this study were 127 grade 7-9 adolescents (male = 65, female = 62) of high depression group (n= 59) and lower depression group (n= 68). The subjects’ status of depression were identified via adolescent’s self-rating on the depression questionnaire (CES-D, a = 0.87) and further validated via teacher assessment. DNA was extracted from saliva, and genotype at rs1824024 was performed for each participant in real time with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY Typer software version 3.4 (Sequenom). Data analysis was performed using the Statistical Package for Social Sciences 17.0 (SPSS 17.0), and chi-square and logistic regression analyses were conducted to depression distributions.
A marginal moderating effect of gender on the association between depression and rs1824024 polymorphism was observed, such that female adolescents with T alleles possessed a decreased risk of depression, but no significant association was found among males. A marginal moderating effect of negative life events on the association between rs1824024 polymorphism and depression was also found. Compared with adolescents carrying GG genotype, adolescents carrying T allele had a decreased risk of depression, but this difference only existed among adolescents reporting low level of negative life events. No moderating effect of grade on the association between rs1824024 polymorphism and depression was found.
The present study lends further support for the theory that acetylcholine may play an important role in depression, and thereby contributes to CHRM2 gene-depression literature by elaborating the moderating effect of negative life events and gender among healthy early adolescents.

Key words: CHRM2 gene, rs1824024 polymorphism, depression, negative life events, early adolescence