The role of COMT gene Val108/158Met polymorphism in suicidal behavior: systematic review and updated meta-analysis

Figures & data

Table 1 Systematic review of the genetic association of Val66Met and SB, characteristics of the studies included

First author	Location	Diagnosis instrument	SB cases	Number of		Mean age		Male/female		Cases			Controls			HWE		NOS
				Cases	Control	Cases	Control	Cases	Control	V-V	V-M	M-M	V-V	V-M	M-M	Cases	Controls
Ohara et al,^Citation20 1998	Japan	DSM-IV	SA	115	135	38.5	–	60/55	–	2	7	3	58	59	18	0.54	0.62	4
Nolan et al,^Citation12 2000	USA, Finland	DSM-IV, DSM-III-R	SA	148	–	42.35	–	42.35	–	44	66	38	–	–	–	–	–	4
Russ et al,^Citation31 2000	USA	DSM-IV	SI	51	51	38	41	32/19	28/23	12	28	9	16	26	7	0.39	0.56	8
Liou et al,^Citation45 2001	Taiwan	DSM-IV	SA	62	188	36.7	38.6	26/36	97/91	36	23	3	98	79	11	0.77	0.45	5
Rujescu et al,^Citation25 2003	Germany	DSM-IV	SA	149	328	40	46	53/96	149/179	35	69	45	78	167	83	0.41	0.82	8
de Luca et al,^Citation26 2005	Canada	SCID I	SA	336	–	35.36	–	128/208	–	–	–	–	–	–	–	–	–	4
Ono et al,^Citation21 2004	Japan		SC	163	169	47.9	47.115	112/51	114/55	68	79	16	90	61	18	0.38	0.13	8
de Luca et al,^Citation13 2006	Canada	SCID I	SA	92	178	42.6	40.6	68/24	129/49	–	–	–	–	–	–	–	–	4
Baud et al,^Citation24 2007	Switzerland, France	STAXI	SA	427	185	38.7	46.08	125/302	130/55	124	218	85	34	107	44	0.55	0.03*	8
Zalsman et al,^Citation47 2008	USA	DSM-IV axis-I and II	SA	486	119	41.6	41.2	209/277	78/41	27	67	25	34	114	53	0.20	0.05	5
Perroud et al,^Citation29 2010	Switzerland, France	DIGS and MINI	SA	875	–	–	–	256/619	–	252	387	183	–	–	–	–	–	4
Nedic et al,^Citation11 2011	Croatia	DSM-IV	–	82	311	50.465	50.74	59/23	253/58	9	38	35	76	170	65	0.78	0.09	7
Pivac et al,^Citation23 2011	Slovenia	–	SA	356	198	48.9	47.1	–	–	78	197	81	45	97	56	0.05	0.88	7
Tovilla-Zárate et al,^Citation33 2011	Mexico	DSM-IV axis-I and II	SA	105	236	30.5	34.5	55/50	132/104	34	58	13	80	112	44	0.15	0.68	6
Calati et al,^Citation7 2011	Germany	SCID I and SCID II	SA	111	289	39.3	45.2	43/68	123/166	23	56	19	79	144	66	0.22	0.98	7
Lee and Him,^Citation27 2011	Korea	DSM-IV	SA	197	170	33.5	36.2	70/127	85/85	94	85	18	69	85	16	0.84	0.23	7
Schosser et al,^Citation32 2012		MINI and HAM-D	SI/SA	68	150	50.75	–	68/182	–	20	33	15	29	93	29	0.81	0.005	7
Du et al,^Citation39 2014	Hungary	DSM-IV	SC	49	72	64.5	48.915	35/14	46/26	16	19	14	22	30	20	0.15	0.16	8
Chen et al,^Citation8 2014	Taiwan	DSM-IV	SA	187	386	32.4	34.3	11/176	168/218	100	78	9	179	170	37	0.25	0.81	6
Pasi et al,^Citation28 2015	India	DSM-IV and C-SSRS	SA	25	–	–	–	20:05	–	13	23	4	–	–	–	–	–	4
Sun et al,^Citation36 2016	People’s Republic of China	DSM-IV-TR axis-I	SA	369	369	44.1	43.9	117/252	117/252	218	129	22	193	161	15	0.66	0.005	7
Antypa et al,^Citation46 2016	Belgium	DSM-IV	SA	213	240	45.99	48.88	63/150	148/192	32	44	23	38	69	39	0.31	0.51	7

Notes: Data not available is indicated with “–”. Statistical significance is indicated with “*”.

Abbreviations: SB, suicidal behavior; V-V, Val-Val; V-M, Val-Met; M-M, Met-Met; DSM, Diagnostic and Statistical Manual of Mental Disorders; SCID, Structured Clinical Interview for DSM-IV; STAXI, State-Trait Anger Expression Inventory; DIGS, Diagnostic Interview for Genetic Studies; HAM-D, Hamilton Depression Rating Scale; C-SSRS: Columbia-Suicide Severity Rating Scale.

Figure 1 Procedures and data analysis.

Notes: (A) Flowchart showing study inclusion and exclusion details. (B) Forest plot of a homozygous model in the overall population. (C) Begg’s funnel plot analysis of publication bias in homozygous models in the overall population. (D) Forest plot of a dominant model in European populations.

Table 2 Meta-analysis results comparing inherence models between cases and controls

Model	Number of studies	Heterogeneity	Random effects, OR (CI 95%)	Z P-value	I^2	Q test P-value	Egger’s test P-value
Overall population
Allelic	14	Large	0.98 (0.84–1.14)	0.85	59.84	0.00	0.12
	13	Absent	1.05 (0.95–1.18)	0.29	19.94	0.24	0.13
Homozygous	14	Large	1.01 (0.74–1.37)	0.93	52.07	0.01	0.33
	13	Absent	1.15 (0.94–1.42)	0.16	0.00	0.46	0.31
Heterozygous	14	Moderate	0.96 (0.80–1.15)	0.68	29.48	0.14	0.18
	12	Absent	1.06 (0.91–1.24)	0.43	0.00	0.52	0.12
Dominant	14	Large	1.03 (0.79–1.34)	0.80	53.88	0.00	0.97
	13	Absent	1.15 (0.97–1.37)	0.10	0.00	0.60	0.62
Recessive	14	Moderate	0.97 (0.80–1.18)	0.80	43.70	0.04	0.08
	12	Absent	1.10 (0.95–1.28)	0.18	0.00	0.49	0.48
Asian populations
Allelic	5	Large	1.02 (0.77–1.35)	0.86	62.20	0.03	0.27
	3	Absent	1.25 (1.04–1.51)	0.01	0.00	0.83	0.65
Homozygous	5	Moderate	1.14 (0.65–2.02)	0.63	42.90	0.13	0.34
	4	Absent	1.32 (0.84–2.05)	0.21	11.62	0.33	0.92
Heterozygous	5	Large	0.98 (0.65–1.46)	0.92	63.99	0.02	0.42
	4	Absent	1.22 (0.93–1.60)	0.14	9.05	0.34	0.14
Dominant	5	Absent	1.20 (0.81–1.78)	0.35	3.37	0.38	0.43
Recessive	5	Large	1.01 (0.68–1.50)	0.95	66.03	0.01	0.35
	3	Absent	1.32 (1.03–1.68)	0.02	0.00	0.99	0.30
European populations
Allelic	5	Large	0.86 (0.65–1.15)	0.32	72.72	0.00	0.58
	4	Absent	1.00 (0.86–1.17)	0.95	0.00	0.77	0.89
Homozygous	5	Large	0.76 (0.44–1.31)	0.33	69.43	0.01	0.42
	4	Absent	1.01 (0.74–1.37)	0.93	0.00	0.80	0.93
Heterozygous	5	Absent	0.86 (0.67–1.11)	0.25	0.00	0.55	0.68
Dominant	5	Large	0.84 (0.52–1.38)	0.50	77.60	0.00	0.79
	4	Absent	1.06 (0.81–1.40)	0.64	15.75	0.31	0.89
Recessive	5	Moderate	0.84 (0.62–1.12)	0.24	29.24	0.22	0.38
	4	Absent	0.94 (0.73–1.21)	0.65	0.00	0.92	0.73
Suicide attempters
Allelic	11	Large	1.01 (0.85–1.21)	0.84	65.25	0.00	0.26
	10	Absent	1.11 (0.99–1.23)	0.05	7.35	0.37	0.22
Homozygous	11	Large	1.05 (0.73–1.51)	0.78	61.35	0.00	0.50
	10	Absent	1.22 (0.97–1.55)	0.08	6.16	0.38	0.64
Heterozygous	11	Absent	1.03 (0.86–1.23)	0.71	18.37	0.26	0.07
Dominant	11	Large	1.05 (0.77–1.44)	0.74	64.00	0.00	0.84
	10	Absent	1.19 (0.98–1.44)	0.07	1.57	0.42	0.99
Recessive	11	Moderate	1.04 (0.84–1.27)	0.69	41.02	0.07	0.03
	10	Absent	1.12 (0.96–1.31)	0.13	0.73	0.43	0.10
Males
Allelic	7	Large	1.00 (0.69–1.43)	0.99	79.31	0.00	0.83
	5	Absent	1.29 (1.04–1.60)	0.01	16.96	0.30	0.74
Homozygous	7	Large	1.07 (0.54–2.13)	0.83	69.29	0.00	0.65
	6	Absent	1.54 (1.04–2.28)	0.02	0.00	0.61	0.50
Heterozygous	7	Large	1.20 (0.64–2.27)	0.55	71.69	0.00	0.84
	6	Absent	1.67 (1.17–2.38)	0.00	0.00	0.52	0.51
Dominant	7	Large	1.17 (0.60–2.24)	0.63	76.26	0.00	0.84
	6	Absent	1.66 (1.18–2.31)	0.00	0.00	0.76	0.32
Recessive	7	Large	0.91 (0.56–1.48)	0.71	76.07	0.00	0.63
	4	Absent	1.04 (0.70–1.53)	0.83	24.20	0.23	0.52
Females
Allelic	7	Moderate	0.83 (0.66–1.03)	0.09	28.30	0.21	0.02
	6	Absent	0.74 (0.59–0.92)	0.00	0.00	0.70	0.26
Homozygous	7	Absent	0.57 (0.37–0.87)	0.01	0.00	0.86	0.54
Heterozygous	7	Absent	0.64 (0.43–0.95)	0.02	0.00	0.48	0.88
Dominant	7	Absent	0.60 (0.41–0.88)	0.00	0.00	0.67	0.92
Recessive	7	Absent	0.86 (0.63–1.18)	0.36	28.65	0.21	0.03
	6	Absent	0.71 (0.51–0.98)	0.03	0.00	0.93	0.33

Note: The data in bold means association.

Figure 2 Meta-regression analysis based on mean age.

Figure 3 Data analysis.

Notes: (A) Forest plot of allelic model in Asian populations. (B) Forest plot of the recessive model in Asian populations. (C) Forest plot of the heterozygous model in suicide attempters. (D) Begg’s funnel plot analysis of publication bias in the heterozygous model in suicide attempters.

Figure 4 Forest plot in the (A) male group in the allelic model, (B) male group in the homozygous model, (C) female group in the dominant model, (D) female group in the recessive model.

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