Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia

Figures & data

Figure 1. Plasma total homocysteine levels of patients with schizophrenia and controls. Blue dots represent plasma total homocysteine levels of patients with SCZ. Red dots represent plasma total homocysteine levels of controls. The mean plasma total homocysteine level in patients with SCZ (n = 42) was 19.5 ± 7.2 nmol/mL (mean ± SD), and the level in the control subjects (n = 42) was 12.4 ± 2.9 nmol/mL (mean ± SD). The plasma total homocysteine levels of the patient group were significant higher than those of the control group (Mann–Whitney U test, p < 0.0001)

Table 1. The top 10-ranking of CpG sites significant associated with plasma homocysteine

Ranking	Probe ID	Minimum beta value across samples	Maximum beta value across samples	Standardized coefficient of plasma total homocysteine	P-value of plasma total homocysteine	Coefficient of age	P-value of age	Coefficient of CP equivalent dose	P-value of CP equivalent dose	Chromo -some	Position*	UCSC RefGene name	UCSC RefGene Group	Relation to UCSC CpG Island
1	cg04579505	0.123	0.272	0.765	5.98E-07	2.10.E-02	2.80.E-01	-5.39.E-04	2.49.E-02	16	67261564	LRRC29	Promoter	CGI shore
2	cg01546563	0.132	0.302	0.701	8.66E-06	7.59.E-02	6.71.E-04	-7.42.E-04	4.63.E-03	8	11567189	GATA4	Gene body	CGI shore
3	cg12423733	0.107	0.375	0.707	1.12E-05	2.22.E-02	2.97.E-01	-4.30.E-04	9.64.E-02	6	29454623	MAS1L	Promoter	Others
4	cg03004330	0.126	0.366	0.695	1.53E-05	6.04.E-02	6.66.E-03	-7.19.E-04	7.19.E-03	10	13934438	FRMD4A	Gene body	CGI shore
5	cg08607821	0.825	0.897	-0.697	2.06E-05	-7.35.E-02	1.55.E-03	2.05.E-04	4.35.E-01	13	24915164	-	Intergenic	CGI shore
6	cg04364311	0.671	0.824	-0.682	3.07E-05	-7.71.E-02	1.01.E-03	2.33.E-04	3.76.E-01	3	101231003	SENP7	Gene body	CGI shore
7	cg23158877	0.131	0.431	-0.685	3.24E-05	-6.68.E-02	4.01.E-03	4.66.E-04	8.42.E-02	11	86012876	C11orf73	Promoter	Others
8	cg05360577	0.134	0.279	0.672	3.62E-05	7.58.E-02	1.17.E-03	-5.40.E-04	4.43.E-02	11	17717629	-	Intergenic	CGI
9	cg24606762	0.101	0.391	0.674	4.10E-05	4.10.E-02	6.80.E-02	-5.92.E-04	3.01.E-02	20	61806972	-	Intergenic	CGI
10	cg11653336	0.756	0.894	-0.675	4.30E-05	-2.80.E-02	2.10.E-01	-1.22.E-05	9.63.E-01	12	133465188	CHFR	Promoter	CGI shore

* Positions refer to Genome Research Consortium human genome build 37 (GRCh37)/UCSC human genome 19 (hg19).

Figure 2. Two CpG sites in the SLC18A2 (cg00498305) and GNAL (cg12327405) genes, which have been implicated in SCZ. A significant positive correlation of plasma total homocysteine with DNA methylation was observed at cg00498305 located in the CGI shore in the promoter region of the SLC18A2 gene (p = 1.67E-03). A significant negative correlation of plasma total homocysteine with DNA methylation was observed at cg12327405 in the CGI in the promoter region of the GNAL gene (p = 2.85E-04). [X-axis: plasma total homocysteine (nmol/mL); Y-axis: DNA methylation (β)]

Figure 3. Percentages of 1,338 CpG sites at which plasma total homocysteine and DNA methylation were significantly correlated. (A) Of the 1,338 CpG sites, 425 (31.8%) were located in promoter regions, 414 (30.9%) were located in gene bodies and 34 (2.5%) were located in 3′−UTRs. (B) Of the 1,338 CpG sites, 212 (15.8%) were located in CGIs, 377 (28.2%) were located in CGI shores and 169 (12.6%) were located in CGI shelves.

Figure 4. Percentage of CpG sites with positive correlations, located in CGIs, CGI shores and CGI shelves. (A) Of the 212 CpG sites located in the CGIs, 152 (71.7%) showed positive correlations between plasma total homocysteine and DNA methylation. (B) Of the 377 CpG sites located in the CGI shores, 189 (50.1%) showed positive correlations between plasma total homocysteine and DNA methylation. (C) Of the 169 CpG sites located in the CGI shelves, 40 (23.7%) showed positive correlations between plasma total homocysteine and DNA methylation.