title: Polymorphisms in genes within the IGF-axis influence antenatal and postnatal growth.
abstract: Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1-17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n = 2642). Of the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of antenatal growth (P ⩽ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P ⩽ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n = 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9% in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.
authors: 1 School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
authors: P G
authors: PG
authors: Parmar
authors: 1 School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
authors: J A
authors: JA
authors: Marsh
authors: 2 The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: H
authors: H
authors: Rob Taal
authors: 5 Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada.
authors: M
authors: M
authors: Kowgier
authors: 3 Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: A G
authors: AG
authors: Uitterlinden
authors: 3 Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: F
authors: F
authors: Rivadeneira
authors: 5 Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada.
authors: L
authors: L
authors: Briollais
authors: 1 School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
authors: J P
authors: JP
authors: Newnham
authors: 3 Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: A
authors: A
authors: Hofman
authors: 5 Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada.
authors: S J
authors: SJ
authors: Lye
authors: 8 Department of Obstetrics Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: E A P
authors: EA
authors: Steegers
authors: 3 Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: C M
authors: CM
authors: van Duijn
authors: 5 Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada.
authors: L J
authors: LJ
authors: Palmer
authors: 2 The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: V W V
authors: VW
authors: Jaddoe
authors: 1 School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
authors: C E
authors: CE
authors: Pennell