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Background: Depression is among the most common psychiatric disorders, and is a leading cause of the global disease burden. Its pathophysiological mechanism is unclear, which limits the development of therapeutic strategies. Long non-coding RNA (lncRNA) single nucleotide polymorphisms (SNPS) may be related. In this study, we aimed to determine the effects of the rs2242385, rs155979, rs3762983, and rs3762984 polymorphisms in the lncRNA NONHSAT102891 on depression susceptibility in a Chinese population. Methods: We conducted a case-control study in a cohort of 480 patients with depression and 329 healthy controls, and performed genotyping by gene sequencing ii. Results: The rs155979 GC genotype was significantly associated with increased risk of depression compared with healthy controls. Stratified analysis showed a 2.08-fold increased risk of suicide in patients with rs155979 GC or GG genotype. The rs2242385, rs3762983, and rs3762984 polymorphisms were not significantly associated with the risk of depression. Haploid analysis showed linkage disequilibrium between rs155979, rs3762983, and rs3762984, and the CCG haplotype reduced the risk of depression. Limitations: The study sample was relatively small, and was restricted to patients from central and southern China. Further, only peripheral blood was used for DNA extraction. Conclusion: The rs155979 polymorphism may be associated with the occurrence of depression in the Chinese population. However, further studies are needed to verify the reliability of our results in large populations and different ethnic groups. [ABSTRACT FROM AUTHOR]