Table 6.
Risk ratios (RR) and 95% confidence intervals from hybrid analyses for interactions between variants in maternal and infant genotypes in genes involved in folate, homocysteine, and transsulfuration pathways and association for risk of congenital heart defects among periconceptional non-Hispanic white users and non-users of serotonin selective reuptake inhibitors (SSRIs), US National Birth Defects Prevention Study, births October 1997-August 2008
| Gene symbol | dbSNP ID | Chromosome | Pathway | Genotype | Non-SSRI users | SSRI users | Interaction D×SSRI×M* | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No† (%) | RR (95% CI) | No† (%) | RR (95% CI) | P value | BFDP‡ | |||||||
| Maternal genotypes | ||||||||||||
| SHMT1 | rs9909104 | 17 | Folate | GG | 84 (6) | 0.85 (0.62 to 1.17) | 8 (10) | 5.57 (1.93 to 16.08) | 7.37×10−4 | 0.76 | ||
| AG | 596 (40) | 0.92 (0.79 to 1.08) | 37 (46) | 2.36 (1.39 to 4.01) | ||||||||
| AA | 795 (54) | Reference | 35 (44) | Reference | ||||||||
| BHMT | rs542852 | 5 | Homocysteine | AA | 172 (12) | 0.90 (0.67 to 1.19) | 14 (17) | 5.48 (1.93 to 15.52) | 9.05×10−4 | 0.76 | ||
| AG | 691 (47) | 0.95 (0.82 to 1.09) | 37 (46) | 2.34 (1.39 to 3.94) | ||||||||
| GG | 614 (42) | Reference | 30 (37) | Reference | ||||||||
| BHMT | rs492842 | 5 | Homocysteine | GG | 198 (13) | 0.98 (0.74 to 1.3) | 14 (17) | 5.43 (1.9 to 15.44) | 1.66×10−3 | 0.79 | ||
| AG | 687 (47) | 0.99 (0.86 to 1.14) | 41 (51) | 2.33 (1.38 to 3.93) | ||||||||
| AA | 590 (40) | Reference | 26 (32) | Reference | ||||||||
| Infant genotypes | ||||||||||||
| MTHFS | rs12438477 | 15 | Folate | AA | 183 (15) | 1.04 (0.77 to 1.42) | 10 (14) | 6.3 (2.31 to 17.06) | 5.36×10−4 | 0.70 | ||
| AC | 603 (48) | 1.02 (0.88 to 1.19) | 35 (50) | 2.51 (1.52 to 4.13) | ||||||||
| CC | 461 (37) | Reference | 25 (36) | Reference | ||||||||
| MTHFS | rs6495446 | 15 | Folate | AA | 91 (7) | 1.02 (0.74 to 1.42) | 6 (8) | 7.73 (4.5 to 23.81) | 6.33 x 10−4 | 0.77 | ||
| AG | 509 (40) | 1.01 (0.86 to 1.19) | 27 (38) | 2.78 (1.58 to 4.88) | ||||||||
| GG | 657 (52) | Reference | 38 (54) | Reference | ||||||||
*Interaction D (disease status)×SSRI×M (maternal genotype) is three way interaction for maternal genotype (see genotype×SSRI model in methods).
†Counts and percentages of maternal genotypes computed on mothers’ genotypes only; counts and percentages of infant genotypes computed on infants’ genotypes only.
‡Bayesian false discovery probability; <0.8 indicates significance.