Table 1. Single-marker association study in 754 adult ADHD patients and 766 sex-matched unrelated controls considering SNPs in (a) microRNA genes and (b) 3′-UTR of experimentally validated target genes.
| SNP (risk allele) |
Genotypes* |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Controls N (%) |
Cases N (%) |
Log-additive (22 vs 12 vs 11) |
Genotypes 11+12 vs 22 |
Genotypes 11 vs 12+22 |
||||||||||
| 11 | 12 | 22 | 11 | 12 | 22 | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | ||
| (a) miRNA | ||||||||||||||
| hsa-miR-128-2 | rs9311107 (T) | 205 (27.4) | 388 (51.9) | 155 (20.7) | 245 (32.9) | 365 (48.9) | 136 (18.2) | 0.064 | 1.18 (1.02–1.40) | 0.028 | 1.18 (0.91–1.52) | 0.224 | 1.30 (1.04–1.61) | 0.022 |
| rs6801590 (A) | 367 (49.2) | 312 (41.8) | 67 (9.0) | 402 (53.8) | 295 (39.5) | 50 (6.7) | 0.103 | 1.19 (1.01–1.39) | 0.035 | 1.36 (0.94–2.00) | 0.099 | 1.20 (0.98–1.47) | 0.074 | |
| hsa-let-7a-1/hsa-let-7f-1/hsa-let-7d | rs7865876 (G) | 320 (43.0) | 352 (47.2) | 73 (9.8) | 371 (50.3) | 308 (41.7) | 59 (8.0) | 0.017 | 1.25 (1.06–1.47) | 6.2e−03 | 1.25 (0.87–1.79) | 0.222 | 1.35 (1.10–1.64) | 4.7e−03 |
| rs8115 (G) | 9 (1.2) | 148 (19.9) | 585 (78.9) | 9 (1.2) | 184 (24.7) | 553 (74.1) | 0.091 | 1.25 (1.00–1.56) | 0.048 | 1.30 (1.02–1.65) | 0.032 | 0.99 (0.39–2.52) | 0.991 | |
| hsa-let-7a-3/hsa-mir-4763/hsa-let-7b | rs9616084 (C) | 432 (58.0) | 275 (37.0) | 37 (5.0) | 476 (64.0) | 236 (31.7) | 32 (4.3) | 0.065 | 1.23 (1.02–1.45) | 0.030 | 1.62 (0.72–1.89) | 0.538 | 1.28 (1.04–1.59) | 0.019 |
| rs6520050 (A) | 309 (41.5) | 346 (46.5) | 89 (12.0) | 339 (45.6) | 337 (45.4) | 67 (9.0) | 0.099 | 1.18 (1.01–1.37) | 0.039 | 1.36 (0.98–1.92) | 0.064 | 1.18 (1.22–1.45) | 0.111 | |
| hsa-miR-34b/hsa-miR-34c | rs28690953 (G) | 18 (2.4) | 178 (23.8) | 553 (73.8) | 23 (3.1) | 231 (31.0) | 492 (65.9) | 3.9e−03 | 1.37 (1.12–1.66) | 1.6e−03** | 1.46 (1.17–1.82) | 8.9e−04** | 1.29 (0.69–2.41) | 0.420 |
| hsa-miR-371/hsa-miR-372/hsa-miR-373 | rs8103186 (C) | 33 (4.4) | 256 (34.3) | 458 (61.3) | 46 (6.2) | 279 (37.3) | 422 (56.5) | 0.099 | 1.20 (1.01–1.43) | 0.033 | 1.22 (0.99–1.50) | 0.058 | 1.42 (0.90–2.25) | 0.132 |
| (b) Gene | ||||||||||||||
| MET | rs1621 (G) | 65 (8.8) | 345 (46.5) | 332 (44.7) | 93 (12.4) | 35 (48.1) | 295 (39.5) | 0.024 | 1.23 (1.06–1.44) | 8.3e–03 | 1.24 (1.01–1.52) | 0.040 | 1.48 (1.06–2.07) | 0.021 |
| rs6566 (G) | 212 (28.8) | 367 (49.9) | 157 (21.3) | 245 (32.8) | 377 (50.5) | 125 (16.7) | 0.048 | 1.19 (1.03–1.39) | 0.017 | 1.35 (1.04–1.75) | 0.024 | 1.20 (0.97–1.39) | 0.096 | |
| NOTCH2 | rs699779 (T) | 561 (75.6) | 164 (22.1) | 17 (2.3) | 596 (79.8) | 146 (19.5) | 5 (0.7) | 0.011 | 1.31 (1.05–1.64) | 0.015 | 3.45 (1.28–9.09) | 7.7e−03 | 1.27 (1.00–1.64) | 0.052 |
| HMGA2 | rs11175982 (T) | 31 (4.2) | 192 (26.0) | 516 (69.8) | 31 (4.1) | 244 (32.6) | 474 (63.3) | 0.019 | 1.23 (1.02–1.47) | 0.026 | 1.34 (1.08–1.67) | 7.5e−03 | 0.99 (0.59–1.64) | 0.957 |
Abbreviations: ADHD, attention deficit hyperactivity disorder; CI, confidence interval; miRNA, microRNA; OR, odds ratio; SNP, single-nucleotide polymorphism; UTR, untranslated region.
*Allele 1 denotes always risk allele and all calculations are performed considering this allele.
**Statistically significant P-values after applying a false discovery rate of 20% (P-value <1.58e−03 for the association tests with SNPs both in the miRNA genes and in the selected target genes).