Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms

Figures & data

Table 1 Summary of polymorphisms identified across analyses

SNP	Chromosome	Minor allele	Genotype distribution (n=70)	HWE
rs10514299	5	T	CC/CT/TT: 57/11/2	0.01
rs1518395	2	A	GG/AG/AA: 30/36/4	0.106
rs2179744	22	A	GG/AG/AA: 36/30/4	0.484
rs11209948	1	G	NA	NA
rs454214	5	A	GG/AG/AA: 18/32/20	0.477
rs301806	1	C	TT/CT/CC: 44/23/3	0.998
rs1475120	6	C	TT/CT/CC: 35/27/8	0.432
rs10786831	10	A	GG/AG/AA: 27/35/8	0.506
rs12552	13	T	CC/CT/TT: 17/38/15	0.469
rs6476606	9	A	GG/AG/AA: 41/25/4	0.941
rs8025231	15	A	CC/AC/AA: 37/26/7	0.451
rs12065553	1	G	AA/AG/GG: 36/31/3	0.245
rs1656369	3	T	AA/AT/TT: 47/21/2	0.85
rs4543289	5	T	NA	NA
rs2125716	12	T	CC/CT: 62/8	0.612
rs2422321	1	G	AA/AG/GG: 53/16/1	0.867
rs7044150	9	T	CC/CT: 65/5	0.757

Abbreviations: HWE, Hardy–Weinberg equilibrium; NA, not available.

Table 2 The effect of diagnosis on FA values (HS > MDD patients)

	P-value*	MNI coordinates (mm)			Voxel size	Tract(s) within clusters
		x	y	z
Cluster1	0.035	−24	29	8	868	Anterior thalamic radiation L Forceps minor Inferior fronto-occipital fasciculus L
Cluster2	0.034	−19	−18	39	661	Corticospinal tract L
Cluster3	0.042	27	32	16	403
Cluster4	0.036	−27	17	−2	270	Inferior fronto-occipital fasciculus L Uncinate fasciculus L
Cluster5	0.042	23	−32	42	191
Cluster6	0.047	19	32	18	85

Note:

* Family-wise error-corrected.

Abbreviations: FA, fractional anisotropy; HS, healthy subjects; L, left; MDD, major depressive disorder; MNI, Montreal Neurological Institute.

Figure 1 A comparison of FA findings between MDD patients and HS.

Note: Axial slices of the cohort’s mean FA skeleton (green) overlaid with red clusters depicting significantly lower FA values (left ATR, IFOF, CST, UF, and forceps minor) in the MDD patients compared to that in HS (FWE-corrected P<0.05).
Abbreviations: ATR, anterior thalamic radiation; CST, corticospinal tract; FA, fractional anisotropy; FWE, family-wise error; HS, healthy subjects; IFOF, inferior fronto-occipital fasciculus; lt., left; MDD, major depressive disorder; UF, uncinate fasciculus.

Figure 2 A comparison of FA findings between T/T individuals (rs301806) and C-carrier individuals with MDD.

Note: Axial slices of the cohort’s mean FA skeleton (green) overlaid with red clusters depicting significantly lower FA values (bilateral IFOF, bilateral ILF, right SLF, and forceps major) in T/T individuals with MDD compared to that in C-carrier individuals with MDD (FWE-corrected P<0.05).
Abbreviations: FA, fractional anisotropy; FWE, family-wise error; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; lt., left; MDD, major depressive disorder; rt, right; SLF, inferior longitudinal fasciculus.

Table 3 The effect of genotype (rs301806) on FA values in MDD (C-carrier individuals > T/T individuals)

	P-value*	MNI coordinates (mm)			Voxel size	Tract(s) within clusters
		x	y	z
Cluster1	0.028	40	−41	−8	5,024	Forceps major Inferior fronto-occipital fasciculus R Inferior longitudinal fasciculus R Superior longitudinal fasciculus R Superior longitudinal fasciculus (temporal part) R
Cluster2	0.04	−41	−40	−7	385	Inferior fronto-occipital fasciculus L Inferior longitudinal fasciculus L
Cluster3	0.045	51	−31	45	355
Cluster4	0.045	−40	−11	−18	194	Inferior longitudinal fasciculus L
Cluster5	0.047	−42	−43	26	122
Cluster6	0.049	−45	−38	8	65

Note:

* Family-wise error-corrected.

Abbreviations: FA, fractional anisotropy; HS, healthy subjects; L, left; MDD, major depressive disorder; MNI, Montreal Neurological Institute; R, right.

Table 4 Demographic and clinical characteristics among four groups regarding the rs301806 SNP

	MDD patients		Healthy subjects		P-value
	C/C and C/T (n=14)	T/T (n=21)	C/C and C/T (n=12)	T/T (n=23)
Male/female	8/6	10/11	7/5	15/8	0.70
Age (years)	46.7±11.8	47.4±17.1	46.2±11.4	43.0±11.0	0.74
HAMD17	20.7±5.3	21.2±6.2			0.80

Note: Data are presented as mean ± SD.

Abbreviations: HAMD17, 17-item Hamilton Rating Scale for Depression; MDD, major depressive disorder; SNP, single-nucleotide polymorphism.

Figure 3 Genotype–diagnosis interactions.

Note: Axial slices of the cohort’s mean FA skeleton (green) overlaid with red clusters depicting a significant genotype–diagnosis interaction in which the lower FA values (left ATR and cingulum, bilateral CST, IFOF, ILF, SLF, UF, forceps major, and forceps minor) in MDD patients compared to that in HS are significantly larger in T/T individuals than in C-carrier individuals (FWE-corrected P<0.05).
Abbreviations: ATR, anterior thalamic radiation; CST, corticospinal tract; FA, fractional anisotropy; FWE, family-wise error; HS, healthy subjects; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; lt., left; MDD, major depressive disorder; rt., right; SLF, inferior longitudinal fasciculus; UF, uncinate fasciculus.

Table 5 The genotype–diagnosis interaction on FA values (rs301806: C-carrier individuals > T/T individuals)

	P-value*	MNI coordinates (mm)			Voxel size	Tract(s) within clusters
		x	y	z
Cluster1	0.012	−10	−9	29	19,599	Anterior thalamic radiation L Corticospinal tract L Corticospinal tract R Cingulum (cingulate gyrus) L Forceps major Forceps minor Inferior fronto-occipital fasciculus L Inferior fronto-occipital fasciculus R Inferior longitudinal fasciculus L Inferior longitudinal fasciculus R Superior longitudinal fasciculus L Superior longitudinal fasciculus R Uncinate fasciculus L Uncinate fasciculus R Superior longitudinal fasciculus (temporal part) L Superior longitudinal fasciculus (temporal part) R
Cluster2	0.031	42	−3	26	1,326	Superior longitudinal fasciculus R
Cluster3	0.042	33	33	22	970	Inferior fronto-occipital fasciculus R
Cluster4	0.036	−32	7	0	638	Inferior fronto-occipital fasciculus L Uncinate fasciculus L
Cluster5	0.047	−16	41	29	187
Cluster6	0.05	17	33	12	117	Forceps minor
Cluster7	0.048	−17	44	23	70
Cluster8	0.048	−15	16	47	57

Note:

* Family-wise error-corrected.

Abbreviations: FA, fractional anisotropy; HS, healthy subjects; L, left; MDD, major depressive disorder; MNI, Montreal Neurological Institute; R, right.