We hypothesized that each copy of the rs1051730 risk allele carried by the mother would be associated with reduced offspring birth weight in women who smoked during the first and/or third trimester of pregnancy. In this group (n = 1829), we observed a trend in the expected direction [per-risk allele change in birth weight = −28 g (95% CI −59 to 2 g); P = 0.07]. We additionally used a triangulation approach and first trimester data to estimate the expected effect size of the association between maternal genotype and offspring birth weight, assuming that it is mediated through the polymorphism's association with smoking quantity. The 95% CIs of our observed effect size estimate in this group included the expected effect size, estimated using the birth weight–smoking quantity and smoking quantity–rs1051730 associations (Supplementary Material, Fig. S1). After adjustment for first trimester smoking quantity, the association with offspring birth weight was −21 g (95% CI −53 to10 g) per maternal risk allele (P = 0.19). There was no association with offspring birth weight in the 5446 women who did not smoke in either the first or third trimester (P = 0.86).
