Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response

Figures & data

Figure 1 SNPs in MIR124-1 and its target RGS4 gene. Three polymorphisms: rs531564 (a functional SNP in MIR124-1), rs10759 (a microRNA-binding site SNP in RGS4), and rs951436 (a promoter SNP in RGS4).

Abbreviation: SNP, single-nucleotide polymorphism.

Table 1 Demographic and clinical characteristics of subjects

Characteristics	Overall (N=103)	Remitters (N=55)	Non-remitters (N=48)	χ^2 or t	p-value	Responders (N=82)	Non-responders (N=21)	χ^2 or t	p-value
Sex
Male, n (%)	48	25 (52.1)	23 (47.9)	0.062	0.803	36 (75.0)	12 (25.0)	1.178	0.278
Female, n (%)	55	30 (54.5)	25 (45.5)			46 (83.6)	9 (16.4)
Age (years)	36.56±12.46	37.42±12.64	32.27±9.69	2.334	0.022	35.09±11.72	34.76±11.40	0.113	0.910
Duration of current episode (months)	17.32±46.94	17.35±53.36	17.29±38.54	0.006	0.995	18.08±51.48	14.05±17.78	0.318	0.751
Duration of illness (months)	51.43±87.39	55.57±114.65	47.18±46.38	0.413	0.681	49.00±94.51	60.41±55.07	−0.461	0.646
Baseline HAMD-17 scores	23.57±2.77	23.20±2.72	24.00±2.80	−1.468	0.145	23.46±2.71	24.00±3.03	−0.739	0.466
Baseline MADRS scores	30.11±4.61	30.11±4.59	30.10±4.68	0.005	0.996	30.09±4.65	30.19±4.59	−0.093	0.926
Baseline CGI scores	4.28±0.60	4.25±0.62	4.31±0.60	−0.486	0.628	4.28±0.61	4.29±0.56	−0.037	0.970

Notes: Bold number represents significant p-value. Data are presented as mean ± standard deviation unless otherwise indicated.

Abbreviations: HAMD-17, 17-item Hamilton Rating Scale for Depression; MADRS, Montgomery–Åsberg Depression Rating Scale; CGI, Clinical Global Impression.

Table 2 Allele and genotype analysis of rs10759, rs531564, and rs951436 between cases and controls

SNPs	N	Allele (%)		χ^2	p-value	MAF (%)	Genotype (%)			χ^2	p-value	OR (95% CI)
rs10759		G	T				GG	GT	TT
Case	219	257 (0.587)	181 (0.413)	2.811	0.094	0.44	74 (0.338)	109 (0.498)	36 (0.164)	2.983	0.225	0.78 (0.51–1.19)
Control	435	468 (0.538)	402 (0.462)				121 (0.278)	226 (0.520)	88 (0.202)
rs531564		C	G				CC	CG	GG
Case	220	76 (0.173)	364 (0.827)	1.167	0.326	0.173	6 (0.027)	64 (0.291)	150 (0.682)	1.148	0.563	1.08 (0.39–2.96)
Control	435	132 (0.152)	738 (0.848)				11 (0.025)	110 (0.253)	314 (0.722)
rs951436		A	C				AA	AC	CC
Case	220	212 (0.482)	228 (0.518)	2.379	0.123	0.41	50 (0.227)	112 (0.509)	58 (0.264)	4.002	0.135	1.08 (0.73–1.60)
Control	436	381 (0.437)	491 (0.563)				93 (0.213)	195 (0.447)	148 (0.339)

Abbreviations: MAF, minor allele frequency; OR, odds ratio; 95% CI, 95% confidence interval; SNPs, single nucleotide polymorphisms.

Figure 2 Hierarchical interaction graphs and interaction dendrogram.

Notes: (A) The values inside boxes indicate information gain (IG) of individual attributes or main effects, whereas values between the nodes exemplify IG of pairwise combinations of attributes or interaction effects. A positive entropy (plotted in red or orange) indicates interaction while a negative entropy (plotted in blue) indicates redundancy. (B) Interaction dendrogram shows that the red line represents synergy interaction and the green line represents synergy interaction more weakly. From left to right, the interaction was more intensive.

Table 3 MDR models of gene–gene interactions

Model	Training bal. ACC	Testing bal. ACC	CV consistency	χ^2	p-value	OR (95% CI)
rs951436	0.5408	0.4881	8/10	4.1687	0.0412	1.46 (1.01–2.09)
rs10759, rs531564	0.5533	0.4769	5/10	5.3841	0.0203	1.47 (1.06–2.04)
rs10759, rs531564, rs951436	0.5676	0.4909	10/10	9.2385	0.0024	1.67 (1.20–2.33)

Abbreviations: MDR, multifactor dimensionality reduction; Training bal. ACC, training-balanced accuracy; CV consistency, cross-validation consistency; OR, odds ratio; 95% CI, 95% confidence interval.

Table 4 The genotype and allele analysis of SNPs between remitters and non-remitters and responders and non-responders

	Genotypea			χ^2	p-valueb	Corrected p-valuec	Allele		χ^2	p-value
rs951436	AA	AC	CC				A	C
Remitters	10	34	10	7.216	0.026	0.078	54	54	0.000	1.000
Non-remitters	15	17	15				47	47
Responders	19	45	16	6.191	0.045	0.135	83	77	1.082	0.298
Non-responders	6	6	9				18	24
rs531564	CC	CG	GG				C	G
Remitters	2	13	39	1.342	0.511	NS	17	91	0.408	0.523
Non-remitters	1	16	30				18	76
Responders	3	23	54	1.436	0.488	NS	29	131	0.342	0.558
Non-responders	0	6	15				6	36
rs10759	GG	GT	TT				G	T
Remitters	23	21	10	3.711	0.156	NS	67	41	0.807	0.369
Non-remitters	20	24	3				64	30
Responders	34	34	12	2.035	0.361	NS	102	58	0.410	0.522
Non-responders	9	11	1				29	102

Notes:

a The genotyping completing rate was 98.05% in a total of 103 samples.

b Bold numbers represent significant p-value.

c Calculated by Bonferroni’s correction.

Abbreviation: NS, nonsignificant.

Figure 3 Percent reduction of HAMD-17 scores of antidepressant treatment across genotypes of rs951436.

Notes: Heterozygous (AC) of rs951436 showed a better response to the antidepressant treatment at week 6 and week 8. The asterisk (*) represents significant p-value.
Abbreviation: HAMD-17, 17-item Hamilton Rating Scale for Depression.

Figure S1 Percent reduction of Hamilton Rating Scale for Depression (HAMD) scores of antidepressant treatment across genotypes of rs10759 (A), rs531563 (B), and rs951436 (C). No significant differences were found between the three polymorphisms and antidepressant.