Gene-gene interaction and new onset of major depressive disorder: Findings from a Chinese freshmen nested case-control study.

Background: The gene-gene interaction is known to be the genetic cause of major depressive disorder (MDD). Several genes have been found to be related to MDD. The objectives of this study were to verify the susceptibility genes of MDD in a sample of university students in China, and to investigate possible gene-gene interactions in relation to the risk of MDD.

Methods: 7,627 Chinese Han freshmen were enrolled at baseline survey in 2018. After a 2-year follow-up, 170 new onset MDD cases and 680 controls with DNA samples reserved were sequenced and genotyped for 4 selected Single Nucleotide Polymorphisms (SNPs) in a nested case-control study (ratio of 1:4). Chi-square test was used to identify the relationships between SNPs and risk of MDD. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interactions.

Results: The 2-year incidence of MDD in Chinese college students was 3.75% (95% CI: 3.24%, 4.34%). There was no statistical difference in MDD incidences between males (3.74%, 95% CI: 3.12%, 4.49%) and females (3.77%, 95% CI: 2.97%, 4.78%) (p>0.05). TMEM161B (rs768705) was positively associated with new onset MDD (χ = 0.75, p = 0.023). The AG genotype of rs768705 was significant (OR=1.640, 95%CI:1.414-2.358). The gene-gene interaction between TMEM161B (rs768705) and LHPP (rs35936514) was statistically significant in this nested case-control study (p = 0.011). The CV consistency was 9/10 and the testing accuracy was 0.5274.

Limitations: The results could not be inferred to other ethnics.

Conclusions: This study provided evidence that combined rs768705 (TMEM161B) and rs35936514 (LHPP) may modulate the risk of MDD.