title: A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: the generation R study.
abstract: 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 -0.23 mm (95%CI -0.45 to -0.00) and -0.41 mm (95%CI -0.69 to -0.13), respectively] and a smaller birth length [difference -2.61 mm (95%CI -5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference -33 grams (95%CI -55 to -10)], and tended to be associated with birth weight [difference -38 grams (95%CI -89 to 13)]. This association persisted after adjustment for smoking quantity.
  
  
  CONCLUSIONS
  Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene--fetal smoke exposure interactions.
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Elisabeth T M
authors.initials: ET
authors.lastname: Leermakers
authors.forename: H Rob
authors.initials: HR
authors.lastname: Taal
authors.forename: Rachel
authors.initials: R
authors.lastname: Bakker
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
mesh_terms: D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005060:Europe; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D009538:Nicotine / Q000378:metabolism; D011247:Pregnancy; D011264:Pregnancy Trimesters; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects*; D014463:Ultrasonography
chemical_list: D009538:Nicotine