Abstract： Objective:To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen.Methods:A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis.Results:The 1-year incidence of MDD among Han freshmen was 2.23% (95% CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95% CI: 1.52%-2.56%) and females (2.39%, 95% CI: 1.98%-2.90%) was not statistically significant ( P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD ( OR=1.98, 95% CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males ( OR=9.61, 95% CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions:There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.