Table 2.
Differentially methylated CpGs in umbilical cord blood DNA associated with prenatal maternal antidepressants in pregnancy
| CpG | Chr | Genomic Position | Gene | Discovery cohort Project Viva (n = 479) | Replication cohort Generation R Study (n = 999c) | ||||
|---|---|---|---|---|---|---|---|---|---|
| Mean (SD) %-DNA methylation | Adjusted % change in DNA methylation (95% CI)a | P | Mean (SD) %-DNA methylation | Adjusted % change in DNA methylation (95% CI)b | P | ||||
| cg00367463 | 1 | 45,249,899 | BEST4 | 1.9 (0.4) | 0.26 (0.16, 0.37) | 2.01 × 10−8 | 10.3 (2.7) | − 0.53 (− 1.02, − 0.03) | 0.04 |
| cg27566858 | 1 | 208,084,099 | CD34 | 2.0 (0.3) | 0.27 (0.15, 0.39) | 3.13 × 10−9 | 12.6 (3.3) | 0.26 (− 0.53, 1.06) | 0.52 |
| cg03536711 | 1 | 221,509,067 | LOC400804 | 53.3 (11.4) | − 11.63 (− 15.80, −7.45) | 3.24 × 10−8 | 54.9 (9.3) | 2.25 (− 1.53, 6.02) | 0.24 |
| cg07729367 | 3 | 128,479,008 | RAB7A | 98.2 (0.5) | − 0.49 (− 0.70, − 0.27) | 1.08 × 10−7 | 90.6 (2.1) | − 0.31 (− 1.36, 0.75) | 0.57 |
| cg22065513 | 3 | 144,241,532 | 97.1 (1.4) | − 1.22 (− 1.73, − 0.72) | 4.11 × 10−9 | 90.7 (2.0) | − 0.36 (− 1.33, 0.61) | 0.47 | |
| cg27299660 | 3 | 171,527,797 | PLD1 | 1.7 (0.4) | 0.77 (0.49, 1.04) | 1.19 × 10−7 | 8.3 (2.3) | 0.11 (− 0.55, 0.77) | 0.75 |
| cg14499053 | 7 | 19,158,954 | 2.2 (0.5) | − 0.33 (− 0.45, − 0.22) | 5.44 × 10−8 | 11.5 (2.1) | 0.35 (− 0.48, 1.19) | 0.41 | |
| cg15881597 | 7 | 73,085,754 | VPS37D | 40.1 (4.9) | − 3.64 (− 5.09, − 2.19) | 5.66 × 10−9 | 47.3 (4.7) | − 1.82 (− 4.06, 0.42) | 0.11 |
| cg06645921 | 12 | 8,025,394 | SLC2A14 | 6.6 (3.7) | − 2.38 (− 2.95, − 1.81) | 9.11 × 10−16 | NA | NA | NA |
| cg27161197 | 12 | 47,224,649 | 71.5 (5.9) | − 5.17 (− 7.12, − 3.23) | 1.77 × 10−9 | 68.9 (5.5) | − 2.01 (− 5.23, 1.21) | 0.22 | |
| cg25121621 | 15 | 45,926,780 | SQRDL | 19.6 (2.9) | 2.74 (1.82, 3.67) | 2.71 × 10−12 | 28.4 (4.2) | − 0.80 (− 4.37, 2.78) | 0.66 |
| cg06358612 | 17 | 28,619,293 | BLMH | 1.4 (0.3) | 0.22 (0.14, 0.31) | 6.07 × 10−8 | 8.1 (1.4) | − 0.18 (− 0.71, 0.34) | 0.49 |
| cg22159528 | 19 | 44,039,727 | ZNF575 | 51.0 (6.8) | − 7.23 (− 10.36, − 4.10) | 1.03 × 10 −8 | 54.7 (5.9) | − 2.46 (− 4.23, − 0.69) | 0.006 |
| cg12489353 | 19 | 48,231,499 | EHD2 | 79.3 (14.5) | − 10 (− 15.7, − 4.3) | 7.88 × 10−8 | 77.2 (10) | − 0.80 (− 6.49, 4.88) | 0.78 |
| cg11449935 | 20 | 35,202,477 | TGIF2 | 2.2 (0.4) | 0.29 (0.16, 0.43) | 4.20 × 10−8 | 10.2 (2.2) | 0.31(− 0.52, 1.13) | 0.47 |
| cg18036763 | 22 | 45,404,910 | PHF21B | 10.2 (3.6) | 3.24 (1.75, 4.74) | 7.62 × 10−8 | 6.2 (1.7) | 0.38 (− 0.34, 1.11) | 0.30 |
Abbreviations: SD standard deviation, CI confidence interval, NA excluded from the replication cohort (Generation R Study) after standard quality control
aAdjusted for maternal age, parity, race/ethnicity, smoking (never, former and during pregnancy), pre-pregnancy BMI, mode of delivery, education and infant sex, gestational age, and estimated cord blood nucleated cells (CD8, CD4, Mono, NK, B cells, granulocytes and nRBCs)
bAdjusted for the same covariates as above and included sample plate as an additional covariate
cRefers to sample size for cg22159528, whereas other models from Generation R Study excluded samples that failed at specific CpG sites (smallest sample size n = 970 for cg18036763)