Background
Materials and methods
Study participants
Characteristic | Control (N = 464) | MDD (N = 439) | BPD (N = 600) | χ2 or F | P value |
---|---|---|---|---|---|
Age (Mean ± SD) | 30.7 ± 12.6 | 29.8 ± 14.9 | 30.5 ± 14.7 | F = 0.431 | 0.650 |
Gender (N (%) female) | 268 (57.8) | 281 (64.0) | 342 (57.0) | χ2 = 5.804 | 0.055 |
Number of hospitalizations (Mean ± SD) | ---- | 1.5 ± 1.4 | 1.9 ± 1.8 | ---- | ---- |
Family history of mental illness (N (%)) | ---- | 72 (16.4) | 122 (20.3) | ---- | ---- |
Age at onset (Mean ± SD) | ---- | 22.1 ± 13.6 | 23.1 ± 11.4 | ---- | ---- |
Education experience (N (%)) | F = 5.630 | 0.466 | |||
Primary school | 33 (7.1) | 35 (8.0) | 44 (7.3) | ||
Junior school | 134 (28.9) | 124 (28.2) | 146 (24.3) | ||
Senior school | 130 (28.0) | 135 (30.8) | 177 (29.5) | ||
College/university | 167 (36.0) | 145 (33.0) | 233 (38.8) | ||
Marriage status (N (%)) | χ2 = 0.964 | 0.617 | |||
Married | 148 (31.9) | 131 (29.8) | 175 (29.2) | ||
Single | 316 (68.1) | 308 (70.2) | 425 (70.8) | ||
Employment status (N (%)) | χ2 = 3.512 | 0.173 | |||
Employed | 205 (44.2) | 167 (38.0) | 248 (41.3) | ||
Unemployed/Retired | 259 (55.8) | 272 (62.0) | 352 (58.7) |
DNA selection
DNA extraction and SNP genotyping
Statistical analysis
Results
Hardy-Weinberg equilibrium analysis of 20 SNPs in all groups
Gene | SNP ID | Position | P value | ||
---|---|---|---|---|---|
Control (N = 464) | MDD (N = 439) | BPD (N = 600) | |||
LEPR
| rs1137101 | chr1:65592830 | 0.330 | 0.999 | 0.430 |
SCN2A
| rs17183814 | chr2:165295879 | 0.829 | 0.510 | 0.999 |
SCN1A
| rs2298771 | chr2:166036278 | 0.768 | 0.188 | 0.803 |
SCN1A
| rs3812718 | chr2:166053034 | 0.699 | 0.620 | 0.307 |
UGT1A9
| rs2741049 | chr2:233673188 | 0.509 | 0.082 | 0.412 |
GSK3B
| rs334558 | chr3:120094435 | 0.999 | 0.999 | 0.728 |
HLA-B
| rs2442736 | chr6:31378844 | 0.615 | 0.999 | 0.642 |
ABCB1
| rs1045642 | chr7:87509329 | 0.059 | 0.605 | 0.335 |
NAT2
| rs1041983 | chr8:18400285 | 0.707 | 0.209 | 0.805 |
NAT2
| rs1801280 | chr8:18400344 | 0.065 | 0.606 | 0.241 |
NAT2
| rs1799929 | chr8:18400484 | 0.144 | 0.063 | 0.257 |
NAT2
| rs1799930 | chr8:18400593 | 0.526 | 0.224 | 0.217 |
NAT2
| rs1208 | chr8:18400806 | 0.354 | 0.239 | 0.257 |
CYP2C19
| rs12248560 | chr10:94761900 | 0.999 | 0.999 | 0.999 |
CYP2C19
| rs4986893 | chr10:94780653 | 0.999 | 0.373 | 0.402 |
CYP2C19
| rs4244285 | chr10:94781859 | 0.123 | 0.648 | 0.999 |
CYP2C9
| rs1057910 | chr10:94981296 | 0.999 | 0.999 | 0.999 |
ANKK1
| rs1800497 | chr11:113400106 | 0.104 | 0.377 | 0.867 |
SH2B1
| rs3888190 | chr16:28878165 | 0.188 | 0.156 | 0.082 |
INSR
| rs2396185 | chr19:7246650 | 0.054 | 0.545 | 0.576 |
Association analysis of genetic predisposition in MDD and BPD
Gene | SNP ID | Genotype distribution | MAF | χ2 |
P
| OR | 95%CI | Statistical power | |||
---|---|---|---|---|---|---|---|---|---|---|---|
LEPR
| rs1137101 | AA | AG | GG | |||||||
Control | 11 | 105 | 348 | 0.1369 | |||||||
MDD | 5 | 86 | 348 | 0.1093 | 3.156 | 0.076 | 0.774 | 0.584–1.027 | 28% | ||
BPD | 10 | 120 | 470 | 0.1167 | 1.943 | 0.163 | 0.833 | 0.644–1.077 | 18% | ||
SCN2A
| rs17183814 | GG | AG | AA | |||||||
Control | 359 | 98 | 7 | 0.1207 | |||||||
MDD | 297 | 131 | 11 | 0.1743 | 10.34 | 0.001 | 1.538 | 1.181–2.001 | 62% | ||
BPD | 416 | 168 | 16 | 0.1667 | 8.841 | 0.003 | 1.457 | 1.136–1.869 | 56% | ||
SCN1A
| rs2298771 | AA | AG | GG | |||||||
Control | 387 | 73 | 4 | 0.0873 | |||||||
MDD | 357 | 75 | 7 | 0.1014 | 1.049 | 0.306 | 1.18 | 0.860–1.618 | 10% | ||
BPD | 498 | 97 | 5 | 0.0892 | 0.023 | 0.879 | 1.024 | 0.757–1.385 | 12% | ||
SCN1A
| rs3812718 | GG | AG | AA | |||||||
Control | 72 | 228 | 164 | 0.4009 | |||||||
MDD | 74 | 206 | 159 | 0.4032 | 0.01 | 0.92 | 1.01 | 0.837–1.219 | 1% | ||
BPD | 100 | 275 | 225 | 0.3958 | 0.055 | 0.814 | 0.979 | 0.822–1.166 | 5% | ||
UGT1A9
| rs2741049 | TT | CT | CC | |||||||
Control | 152 | 221 | 91 | 0.4343 | |||||||
MDD | 149 | 198 | 92 | 0.4351 | 0.001 | 0.972 | 1.003 | 0.833–1.209 | 5% | ||
BPD | 167 | 309 | 124 | 0.4642 | 1.889 | 0.169 | 1.128 | 0.950–1.341 | 16% | ||
GSK3B
| rs334558 | TT | CT | CC | |||||||
Control | 56 | 212 | 196 | 0.3491 | |||||||
MDD | 54 | 200 | 185 | 0.3508 | 0.005 | 0.941 | 1.007 | 0.830–1.222 | 5% | ||
BPD | 83 | 287 | 230 | 0.3775 | 1.816 | 0.178 | 1.13 | 0.946–1.351 | 15% | ||
HLA-B
| rs2442736 | GG | GC | CC | |||||||
Control | 422 | 42 | 0 | 0.0453 | |||||||
MDD | 385 | 53 | 1 | 0.0626 | 2.682 | 0.102 | 1.41 | 0.933–2.130 | 23% | ||
BPD | 544 | 54 | 2 | 0.0483 | 0.111 | 0.74 | 1.071 | 0.713–1.609 | 6% | ||
ABCB1
| rs1045642 | CC | CT | TT | |||||||
Control | 137 | 249 | 78 | 0.4364 | |||||||
MDD | 177 | 208 | 54 | 0.3599 | 11.01 | 0.001 | 0.726 | 0.601–0.877 | 67% | ||
BPD | 244 | 268 | 88 | 0.3700 | 9.628 | 0.002 | 0.758 | 0.637–0.903 | 61% | ||
NAT2
| rs1041983 | CC | CT | TT | |||||||
Control | 144 | 225 | 95 | 0.4472 | |||||||
MDD | 130 | 230 | 79 | 0.4419 | 0.051 | 0.821 | 0.979 | 0.813–1.179 | 5% | ||
BPD | 182 | 300 | 118 | 0.4467 | 0.001 | 0.981 | 0.998 | 0.840–1.186 | 5% | ||
NAT2
| rs1801280 | TT | CT | CC | |||||||
Control | 416 | 40 | 8 | 0.0603 | |||||||
MDD | 400 | 38 | 1 | 0.0456 | 1.96 | 0.162 | 0.743 | 0.490–1.127 | 17% | ||
BPD | 554 | 44 | 2 | 0.0400 | 4.66 | 0.031 | 0.649 | 0.437–0.964 | 33% | ||
NAT2
| rs1799929 | CC | CT | TT | |||||||
Control | 430 | 32 | 2 | 0.0388 | |||||||
MDD | 390 | 45 | 4 | 0.0604 | 4.481 | 0.034 | 1.592 | 1.032–2.456 | 33% | ||
BPD | 553 | 45 | 2 | 0.0408 | 0.057 | 0.812 | 1.055 | 0.680–1.636 | 36% | ||
NAT2
| rs1799930 | GG | AG | AA | |||||||
Control | 264 | 176 | 24 | 0.2414 | |||||||
MDD | 231 | 182 | 26 | 0.2665 | 1.506 | 0.22 | 1.142 | 0.924–1.412 | 14% | ||
BPD | 312 | 250 | 38 | 0.2717 | 2.505 | 0.114 | 1.172 | 0.963–1.427 | 20% | ||
NAT2
| rs1208 | AA | AG | GG | |||||||
Control | 416 | 44 | 4 | 0.0560 | |||||||
MDD | 400 | 37 | 2 | 0.0467 | 0.805 | 0.37 | 0.825 | 0.542–1.256 | 11% | ||
BPD | 553 | 45 | 2 | 0.0408 | 2.675 | 0.102 | 0.717 | 0.481–1.070 | 27% | ||
CYP2C19
| rs12248560 | CC | CT | TT | |||||||
Control | 460 | 4 | 0 | 0.0043 | |||||||
MDD | 434 | 5 | 0 | 0.0057 | 0.174 | 0.676 | 1.323 | 0.354–4.943 | ---- | ||
BPD | 594 | 6 | 0 | 0.0050 | 0.053 | 0.818 | 1.161 | 0.327–4.125 | ---- | ||
CYP2C19
| rs4986893 | GG | AG | AA | |||||||
Control | 440 | 24 | 0 | 0.0259 | |||||||
MDD | 393 | 44 | 2 | 0.0547 | 9.781 | 0.002 | 2.178 | 1.323–3.588 | 66% | ||
BPD | 536 | 64 | 0 | 0.0533 | 9.962 | 0.002 | 2.122 | 1.317–3.420 | 67% | ||
CYP2C19
| rs4244285 | GG | AG | AA | |||||||
Control | 256 | 168 | 40 | 0.2672 | |||||||
MDD | 219 | 179 | 41 | 0.2973 | 2.009 | 0.156 | 1.16 | 0.945–1.424 | 17% | ||
BPD | 275 | 263 | 62 | 0.3225 | 7.633 | 0.006 | 1.305 | 1.080–1.577 | 50% | ||
CYP2C9
| rs1057910 | AA | AC | CC | |||||||
Control | 433 | 31 | 0 | 0.0334 | |||||||
MDD | 406 | 33 | 0 | 0.0376 | 0.231 | 0.631 | 1.13 | 0.686–1.862 | 6% | ||
BPD | 568 | 32 | 0 | 0.0267 | 0.827 | 0.363 | 0.793 | 0.480–1.309 | 10% | ||
ANKK1
| rs1800497 | GG | AG | AA | |||||||
Control | 168 | 208 | 88 | 0.4138 | |||||||
MDD | 143 | 224 | 72 | 0.4191 | 0.053 | 0.818 | 1.022 | 0.848–1.233 | 5% | ||
BPD | 202 | 290 | 108 | 0.4217 | 0.133 | 0.715 | 1.033 | 0.868–1.229 | 6% | ||
SH2B1
| rs3888190 | CC | AC | AA | |||||||
Control | 396 | 63 | 5 | 0.0787 | |||||||
MDD | 365 | 68 | 6 | 0.0911 | 0.902 | 0.342 | 1.174 | 0.843–1.636 | 10% | ||
BPD | 498 | 93 | 9 | 0.0925 | 1.268 | 0.26 | 1.194 | 0.877–1.625 | 12% | ||
INSR
| rs2396185 | AA | AC | CC | |||||||
Control | 336 | 124 | 4 | 0.1422 | |||||||
MDD | 328 | 101 | 10 | 0.1378 | 0.073 | 0.786 | 0.964 | 0.739–1.258 | 5% | ||
BPD | 408 | 171 | 21 | 0.1775 | 4.789 | 0.029 | 1.301 | 1.027–1.648 | 33% |
Linkage disequilibrium analysis and haplotype analysis
rs4986893 | rs4244285 | Control(n = 464) | MDD(n = 439) | BPD(n = 600) | ||
---|---|---|---|---|---|---|
Haplotype 1 | G | G | 656 | 569 | 750 | |
Haplotype 2 | G | A | 248 | 261 | 386 | |
Haplotype 3 | A | G | 24 | 48 | 64 | |
MDD | BPD | |||||
χ2 |
P
| OR (CI 95%) | χ2 |
P
| OR (95% CI) | |
Overall | 13.137 | 0.001 | –– | 20.065 | < 0.001 | –– |
2 vs. 1 | 3.359 | 0.067 | 1.213 (0.987, 1.492) | 10.068 | 0.002 | 1.361(1.125, 1.648) |
3 vs. 1 | 11.145 | 0.001 | 2.306(1.395, 3.812) | 12.549 | < 0.001 | 2.332 (1.442, 3.772) |
CYP2C19 metabolizer status distribution in controls and cases
Control(n = 464) | MDD(n = 439) | BPD(n = 600) | ||||
---|---|---|---|---|---|---|
NM | 248 (53.45%) | 187 (42.60%) | 233 (38.83%) | |||
IM | 160 (34.48%) | 195 (44.42%) | 283 (47.17%) | |||
PM | 56 (12.07%) | 57 (12.98%) | 84 (14.00%) | |||
IM&PM | 216 (46.55%) | 252 (57.40%) | 367 (61.17%) | |||
MDD | BPD | |||||
χ2 |
P
| OR (CI 95%) | χ2 |
P
| OR (95% CI) | |
NM vs. IM vs. PM | 11.330 | 0.003 | –– | 23.215 | < 0.001 | –– |
IM&PM vs. NM | 10.639 | 0.001 | 1.547(1.190,2.012) | 22.563 | < 0.001 | 1.808(1.415,2.311) |