title: Variants near CCNL1/LEKR1 and in ADCY5 and fetal growth characteristics in different trimesters.
abstract: BACKGROUND
  A recent genome-wide association study identified variants near CCNL1/LEKR1 (rs900400) and in ADCY5 (rs9883204) to be associated with birth weight. We examined the associations of these variants with fetal growth characteristics in different trimesters, with a main interest in the timing of the associations and the affected body proportions.
  
  
  METHODS
  We used data from two prospective cohort studies from fetal life onward in The Netherlands and Australia. Repeated fetal ultrasound examinations were performed to measure head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Analyses were based on a total group of 3909 subjects.
  
  
  RESULTS
  The C-allele of rs900400 was associated in second trimester with smaller fetal HC and FL, and in third trimester with smaller HC, AC, FL, and EFW. For each C-allele, the combined effect estimate for EFW in third trimester was -18.6 g (95% confidence interval, -27.5, -9.7 g; P = 4.2 × 10(-5)). The C-allele of rs9883204 was not associated with fetal growth characteristics in second trimester but was associated with restriction of all growth characteristics, except HC, in third trimester and at birth. For each C-allele, the combined effect estimate was -16.9 g (95% confidence interval, -26.8, -7.0 g; P = 8.4 × 10(-4)) for EFW in third trimester. Both genetic variants were associated with lower birth and placenta weight.
  
  
  CONCLUSIONS
  Our results suggest that a genetic variant of rs900400 leads to symmetric growth restriction from early pregnancy onward, whereas a genetic variant of rs9883204 leads to asymmetric growth restriction, characterized by a relatively larger HC, from third trimester.
authors.affiliation: The Generation R Study Group and Department of Epidemiology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Mook-Kanamori
authors.forename: Julie A
authors.initials: JA
authors.lastname: Marsh
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.forename: H Rob
authors.initials: HR
authors.lastname: Taal
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Lawrie J
authors.initials: LJ
authors.lastname: Beilin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000328:Adult; D000483:Alleles; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016213:Cyclins / Q000235:genetics*; D003627:Data Interpretation, Statistical; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000235:genetics* / Q000502:physiology; D011446:Prospective Studies; D014904:Western Australia / Q000453:epidemiology
chemical_list: C468873:CCNL1 protein, human; D016213:Cyclins; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V