Comparison of SCL-90 factor scores of coal miners with the national norm in China
Compared with the national norm[29], the SCL-90 scores of coal miners showed statistically significant differences (P<0.05), except in the case of the interpersonal sensitivity factor (P<0.05). The scores of other factors of coal miners were lower than the national norm, and the scores of other factors were higher than the national norm. Table 2
Table 2. SCL-90 scores of coal miners compared with domestic norms
Variables
|
Coal miner(n=1675)
|
Chinese norms(n=1338)
|
t
|
P
|
Somatization
|
1.53±0.61
|
1.37±0.48
|
7.848
|
<0.001
|
Compulsive Symptoms
|
1.74±0.63
|
1.62±0.58
|
5.380
|
<0.001
|
Interpersonal Sensitivity
|
1.62±0.65
|
1.65±0.61
|
-1.294
|
0.196
|
Depression
|
1.58±0.65
|
1.50±0.59
|
3.496
|
<0.001
|
Anxiety
|
1.46±0.57
|
1.39±0.43
|
3.725
|
<0.001
|
Hostility
|
1.54±0.62
|
1.48±0.56
|
2.754
|
0.006
|
Fear
|
1.34±0.52
|
1.23±0.41
|
6.325
|
<0.001
|
Paranoia
|
1.48±0.60
|
1.43±0.57
|
2.324
|
0.020
|
Psychosis
|
1.41±0.54
|
1.29±0.42
|
6.674
|
<0.001
|
Another Factors
|
1.60±0.63
|
1.65±0.61
|
-2.195
|
0.028
|
SCL-90 Total Score
|
138.27±49.13
|
129.96±38.76
|
5.056
|
<0.001
|
Mental health status of coal miners under different MSDs conditions
The SCL-90 factor scores of coal miners with different MSDs disease conditions were compared, and the scores of all factors in the MSDs group were higher than those in the Non-MSDs group (P<0.001). Table 3
Table 3. Mental health status of coal mine workers under different MSDs
Variables
|
Non-MSDs(n=727)
|
MSDs(n=948)
|
t
|
P
|
Somatization
|
1.33±0.48
|
1.68±0.66
|
-12.179
|
<0.001
|
Compulsive Symptoms
|
1.56±0.52
|
1.88±0.67
|
-10.619
|
<0.001
|
Interpersonal Sensitivity
|
1.45±0.52
|
1.75±0.72
|
-9.603
|
<0.001
|
Depression
|
1.39±0.53
|
1.72±0.69
|
-10.865
|
<0.001
|
Anxiety
|
1.31±0.45
|
1.58±0.62
|
-10.020
|
<0.001
|
Hostility
|
1.35±0.50
|
1.68±0.67
|
-11.077
|
<0.001
|
Fear
|
1.23±0.43
|
1.42±0.57
|
-7.451
|
<0.001
|
Paranoia
|
1.34±0.50
|
1.59±0.65
|
-8.815
|
<0.001
|
Psychosis
|
1.27±0.43
|
1.52±0.58
|
-9.631
|
<0.001
|
Another Factors
|
1.43±0.53
|
1.74±0.66
|
-10.302
|
<0.001
|
SCL-90 Total Score
|
123.14±39.34
|
149.88±52.63
|
-11.462
|
<0.001
|
Hardy-Weinberg genetic balance test
The genotype distribution frequency of the BDNF gene and the TPH-2 gene was analyzed using the Hardy-Weinberg genetic balance test between the case group and the control group. There was no statistical significance in the distribution of the actual value and the expected value of BDNF (rs6265, rs10835210) gene polymorphisms and TPH-2 (rs4570625, rs4131347) gene polymorphisms in the case group and the control group (P>0.05). Table 4
Table 4. Genetic locus Hardy-Weinberg genetic balance test
Gene
|
Genotype
|
Case group
|
χ2
|
P
|
Control group
|
χ2
|
P
|
Actual
value
|
Expectation values
|
Actual
value
|
Expectation values
|
BDNF
|
rs6265
|
|
|
|
|
|
|
|
|
AA
|
65
|
71.3
|
2.555
|
0.110
|
50
|
52.9
|
0.545
|
0.460
|
AG
|
137
|
124.4
|
130
|
124.2
|
GG
|
48
|
54.3
|
70
|
72.9
|
rs10835210
|
|
|
|
|
|
|
|
|
AA
|
27
|
32.8
|
2.489
|
0.115
|
16
|
20.7
|
2.134
|
0.144
|
AC
|
127
|
115.5
|
112
|
102.5
|
CC
|
96
|
101.8
|
122
|
126.7
|
TPH-2
|
rs4570625
|
|
|
|
|
|
|
|
|
GG
|
76
|
82.9
|
3.234
|
0.072
|
58
|
60.5
|
0.405
|
0.524
|
GT
|
136
|
122.1
|
130
|
125.0
|
TT
|
38
|
44.9
|
62
|
64.5
|
rs4131347
|
|
|
|
|
|
|
|
|
CC
|
70
|
68.6
|
0.118
|
0.731
|
77
|
71.3
|
2.107
|
0.147
|
CG
|
122
|
124.7
|
113
|
124.4
|
GG
|
58
|
56.6
|
60
|
54.3
|
Genotypes and allele frequencies of BDNF and TPH-2
Except for TPH-2 rs4131347 gene polymorphism, the genotype and allele distribution frequency of BDNF (rs6265, rs10835210) and TPH-2 rs4570625 gene polymorphisms showed statistical significance between the case group and the control group (P<0.05). The results suggested that rs6265 and rs10835210 of the BDNF gene and rs4570625 of the TPH-2 gene were associated with the occurrence of mental disorders. Table 5
Table 5. Distribution frequency of BDNF, TPH-2 genotypes, and alleles in the case group and control group
Gene
|
Genotype/allele
|
Case group(%)
|
Control group(%)
|
χ2
|
P
|
BDNF rs6265
|
AA
|
65(26.0)
|
50(20.0)
|
6.242
|
0.044
|
AG
|
137(54.8)
|
130(52.0)
|
GG
|
48(19.2)
|
70(28.0)
|
A
|
267(53.4)
|
230(46.0)
|
5.476
|
0.019
|
G
|
233(46.6)
|
270(54.0)
|
BDNF rs10835210
|
AA
|
27(10.8)
|
16 (6.4)
|
6.856
|
0.032
|
AC
|
127(50.8)
|
112(44.8)
|
CC
|
96(38.4)
|
122(48.8)
|
A
|
181(36.2)
|
144(28.8)
|
6.240
|
0.013
|
C
|
319(63.8)
|
356(71.2)
|
TPH-2 rs4570625
|
GG
|
76(30.4)
|
58(23.2)
|
8.313
|
0.016
|
GT
|
136(54.4)
|
130(52.0)
|
TT
|
38(15.2)
|
62(24.8)
|
G
|
288(57.6)
|
246(49.2)
|
7.089
|
0.008
|
T
|
212(42.4)
|
254(50.8)
|
TPH-2 rs4131347
|
CC
|
70(28.0)
|
77(30.8)
|
0.712
|
0.701
|
CG
|
122(48.8)
|
113(45.2)
|
GG
|
58(23.2)
|
60(24.0)
|
C
|
262(52.4)
|
267(53.4)
|
0.100
|
0.751
|
G
|
238(47.6)
|
233(46.6)
|
Correlation analysis of BDNF gene haplotypes and mental disorders
Based on linkage-disequilibrium across gene loci, we determined the following: the BDNF gene rs6265 locus and rs10835210 coefficient D'=0.070, R2 =0.002, Global chi-square= 35.690, and genotype distribution frequency >0.03. The results suggested that the linkage imbalance between rs6265 and rs10835210 was not obvious. Four haplotypes (A-A, A-C, G-A, and G-C) were constructed using the software. The distribution of A-A haplotypes and G-A haplotypes was statistically different between the case group and the control group (P<0.05), and A-A haplotypes were identified as the risk factors for mental disorders, while G-A haplotypes were protective factors for mental disorders. Figure 1, Table 6
Table 6. Analysis of the association between haplotypes of BDNF gene SNPs and mental disorders
Haplotype
|
Case group(%)
|
Control group(%)
|
χ2
|
P
|
OR(95%CI)
|
A-A
|
105.82(21.2)
|
40.82 (8.2)
|
33.760
|
<0.001
|
3.020(2.054~4.440)
|
A-C
|
161.18(32.2)
|
189.18(37.8)
|
3.444
|
0.064
|
0.782(0.602~1.014)
|
G-A
|
75.18(15.0)
|
103.18(20.6)
|
5.348
|
0.021
|
0.681(0.491~0.944)
|
G-C
|
157.82(31.6)
|
166.82(33.4)
|
0.370
|
0.543
|
0.921(0.707~1.200)
|
Correlation analysis of TPH-2 gene haplotypes and mental disorders
The results showed the following: The linkage-disequilibrium coefficient D'=0.161, R2 =0.020, Global chi-square= 8.084, and the genotype distribution frequency was >0.03 for TPH-2 gene rs4570625 and rs4131347. The results suggested that the linkage-disequilibrium between rs4570625 and rs4131347 was not obvious. The software constructed G-C, G-G, T-C, and T-G haplotypes. The distribution of G-C haplotypes and T-C haplotypes was statistically different between the case group and the control group (P<0.05), and T-C haplotypes were a risk factor for mental disorders, while G-C haplotypes were a protective factor for mental disorders. Figure 2, Table 7
Table 7. Analysis of the association between haplotypes of TPH-2 gene SNPs and mental disorders
Haplotype
|
Case group(%)
|
Control group(%)
|
χ2
|
P
|
OR(95%CI)
|
G-C
|
110.00(22.0)
|
137.71(27.5)
|
4.120
|
0.042
|
0.742(0.556~0.990)
|
G-G
|
136.00(27.2)
|
150.29(30.1)
|
0.999
|
0.317
|
0.869(0.661~1.144)
|
T-C
|
157.00(31.4)
|
124.29(24.9)
|
5.292
|
0.021
|
1.384(1.049~1.825)
|
T-G
|
97.00(19.4)
|
87.71(17.5)
|
0.573
|
0.449
|
1.131(0.822~1.558)
|
GMDR constructs the gene-environment interaction model
GMDR software was used to analyze the interaction of BDNF gene, TPH-2 gene, and MSDs gene on psychological disorders. The cross-consistency coefficient of the interaction model between MSDs and BDNF gene rs6265, and TPH-2 gene rs4570625 was the highest (10/10). The accuracy of the training set was 0.66 and the accuracy of the test set was 0.62, which was statistically significant (P=0.011). The results showed that MSDs interacted with BDNF rs6265 and TPH-2 rs4570625. Table 8, Figure 3. The tree diagram showed that there was a strong positive interaction between TPH-2 gene rs4570625 and MSDs. Figure 4.
Table 8. GMDR: A gene-environment interaction model
Model
|
Precision
|
Sign test
|
Cross validation
Consistency coefficient
|
training set
|
test set
|
χ2
|
P
|
MSDs
|
0.56
|
0.52
|
6
|
0.377
|
7/10
|
TPH-2 rs4570625*MSDs
|
0.62
|
0.60
|
10
|
0.001
|
10/10
|
BDNF rs6265*TPH-2 rs4570625*MSDs
|
0.66
|
0.62
|
9
|
0.011
|
10/10
|
Logistic regression analysis of the gene-environment interaction
Mental disorders were taken as the dependent variable. Then, combined with the GMDR results, MSDs, MSDs *rs4570625, and MSDs *rs6265*rs4570625 were introduced into the equation for further logistic regression analysis of gene-environment interactions. The results showed that rs4570625(GG)*MSDs (OR=6.000,95%CI:1.723-20.889)、rs4570625(GT)*rs6265(AA)*MSDs(OR=12.444,95%CI:3.031-51.079)、rs4570625(GT)*rs6265(AG)*MSDs(OR=5.765,95%CI:1.530-21.718). Gene-environment interactions are risk factors for mental disorders. Figure 5.