DNA hypomethylation of the OLFM1 gene in patients with depression

Depression is a heterogeneous psychiatric disorder and a growing public health concern, characterized by its high prevalence, recurrence rate, and association with suicide. There is evidence suggesting that both genetic susceptibility and environmental factors can regulate gene expression through DNA methylation, thereby influencing the occurrence and development of depression. The olfactory sensory neuropeptide 1 (OLFM1) protein is a risk factor for mental disorders. However, there are no reports yet regarding the correlation between the OLFM1 gene and depression, nor have there been any studies on the association between OLFM1 gene DNA methylation and depression.

Genomic DNA was extracted from peripheral blood samples of patients with depression (n = 100) and healthy controls (n = 100) using the QIAamp DNA Blood Mini Kit. Subsequently, the extracted genomic DNA was subjected to bisulfite treatment using the EZ DNA Methylation-Gold™ kit. DNA methylation levels of 107 CpG sites in six fragments of OLFM1 exon 1 and its downstream were detected by the Illumina HiSeq platform using MethylTarget™ technology.

Methylation levels across the overall OLFM1 CpG island and its six fragments (OLFM1-1 to OLFM1-6) were significantly reduced in the depression group relative to controls. Analysis of the OLFM1 gene fragments revealed that 84 of 107 CpG sites were significantly hypomethylated in depressed individuals. When patients were divided by sex, male patients displayed hypomethylation at 65 CpG sites, substantially more than the 37 sites found in females.

OLFM1 hypomethylation is associated with depression and may serve as a potential epigenetic biomarker.