A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: the Generation R

Objective: Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics. Methods: This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy. Results: Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences 20.23 mm (95%CI 20.45 to 20.00) and 20.41 mm (95%CI 20.69 to 20.13), respectively] and a smaller birth length [difference 22.61 mm (95%CI 25.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference 233 grams (95%CI 255 to 210)], and tended to be associated with birth weight [difference 238 grams (95%CI 289 to 13)]. This association persisted after adjustment for smoking quantity