DNA Methylation Changes in Intron 1 of Triggering Receptor Expressed on Myeloid Cell 2 in Japanese Schizophrenia Subjects

A hypothesis for schizophrenia (SCZ) called the "microglia hypothesis" has been suggested. In SCZ, expression of triggering receptor expressed on myeloid cell 2 (TREM2) mRNA is higher in leukocytes than in healthy individuals. Here, the methylation rates of four CpG sites in TREM2 intron 1 that may bind important transcription factors and the correlation between the methylation rate and mRNA expression were determined. We compared the methylation rates in SCZ patients and age-matched controls (n = 50 each). SCZ patients had significantly lower methylation rates of CpG 2 (17.0 ± 6.7 vs. 20.2 ± 5.0; p = 0.02) and CpG 3 (23.8 ± 8.2 vs. 28.1 ± 6.2; p = 0.01). The average methylation rate (15.3 ± 5.2 vs. 17.6 ± 3.9; p = 0.009) was also lower. A significant negative correlation was found between TREM2 mRNA expression and the methylation rate of CpG 2 (r = -0.252, p = 0.012). SCZ susceptibility markers may include low methylation at TREM2 intron 1 and increased TREM2 mRNA levels. Our pilot study requires validation with higher numbers of participants and with other myeloid cell types.