Table 3.
Multiple regression of phenotypes was performed on perinatal women, adjusted for race, ethnicity, age, and history of anxiety or depression, using coefficients from terms on additive gene effects (ADD), deviation from dominance (DOMDEV), and the joint effect of ADD and DOMDEV (GENO-2DF).
| Coefficient |
GENO_2DF |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical outcome | Chr: base (hg19) | SNP | Allele | Symbol | Transcript | global genomeAD MAF (n subjects) | Test | β | SE | 95% CI | T | P | T | P | H–B |
| Pain right now (six weeks postpartum) | chr22: 19,950,485 | rs4633 | C/T | COMT | ENST 00000361682 | 0.4626 (140,690) | ADD | −0.33 | 0.11 | −0.54 to −0.13 | −3.18 | 0.002 | 14.35 | 0.0008 | 0.029 |
| DOMDEV | −0.23 | 0.10 | −0.43 to −0.02 | −2.19 | 0.03 | ||||||||||
| Labor pain unpleasantness max score (labor) | chr5: 164,523,472 | rs11135349 | A/C | Intergenic | ENST 00000519570 | 0.614 (15,683) | ADD | −0.43 | 0.11 | −0.65 to −0.21 | −3.83 | 0.0003 | 16.69 | 0.0002 | 0.009 |
| DOMDEV | 0.20 | 0.10 | −0.004 to 0.40 | 1.93 | 0.058 | ||||||||||
| chr1: 177,026,733 | rs7548151 | G/A | ASTN1 | ENST 00000361833 | 0.1345 (15,684) | ADD | −0.60 | 0.15 | −0.89 to −0.31 | −4.1 | 0.0001 | 18.8 | 8.3 × 10−5 | 0.003 | |
| DOMDEV | 0.59 | 0.15 | 0.29 to 0.88 | 3.9 | 0.0002 | ||||||||||
Note: These findings support that alleles increase risk for the pain phenotypes, specifically for additive gene effects (both “pain right now at six weeks postpartum” and “labor pain unpleasantness maximum score” phenotypes) and for DOMDEV effects (“pain right now at six weeks postpartum” phenotype). The relationships between rs4633 and “pain right now at six weeks postpartum” and rs11135349, rs7548151, and labor pain unpleasantness maximum score were significant for the joint test that accounted for both additive and dominant-deviance models, after considering multiple comparisons using Holm–Bonferroni family-wise error rate (H–B), where tests with H–B rate < 0.05 were considered significant. H–B: Holm–Bonferroni family-wise error rate; CI: confidence interval; Chr: chromosome; SE: standard error; T: student t test; β: regression coefficient; ADD: additive gene effect model; DOMDEV: deviation from dominance effect model; GENO_2DF: joint test of the coefficients for ADD and DOMDEV models; SNP: single-nucleotide polymorphism; MAF: minor allele frequency.