title: Adult height variants affect birth length and growth rate in children.
abstract: Previous studies identified 180 single nucleotide polymorphisms (SNPs) associated with adult height, explaining ∼10% of the variance. The age at which these begin to affect growth is unclear. We modelled the effect of these SNPs on birth length and childhood growth. A total of 7768 participants in the Avon Longitudinal Study of Parents and Children had data available. Individual growth trajectories from 0 to 10 years were estimated using mixed-effects linear spline models and differences in trajectories by individual SNPs and allelic score were determined. The allelic score was associated with birth length (0.026 cm increase per 'tall' allele, SE = 0.003, P = 1 × 10(-15), equivalent to 0.017 SD). There was little evidence of association between the allelic score and early infancy growth (0-3 months), but there was evidence of association between the allelic score and later growth. This association became stronger with each consecutive growth period, per 'tall' allele per month effects were 0.015 SD (3 months-1 year, SE = 0.004), 0.023 SD (1-3 years, SE = 0.003) and 0.028 SD (3-10 years, SE = 0.003). By age 10, the mean height difference between individuals with ≤170 versus ≥191 'tall' alleles (the top and bottom 10%) was 4.7 cm (0.8 SD), explaining ∼5% of the variance. There was evidence of associations with specific growth periods for some SNPs (rs3791675, EFEMP1 and rs6569648, L3MBTL3) and supportive evidence for previously reported age-dependent effects of HHIP and SOCS2 SNPs. SNPs associated with adult height influence birth length and have an increasing effect on growth from late infancy through to late childhood. By age 10, they explain half the height variance (∼5%) of that explained in adults (∼10%).
authors.affiliation: MRC Centre for Causal Analyses in Translational Epidemiology, School of Social & Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. l.paternoster@bristol.ac.uk
authors.forename: Lavinia
authors.initials: L
authors.lastname: Paternoster
authors.forename: Laura D
authors.initials: LD
authors.lastname: Howe
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: John P
authors.initials: JP
authors.lastname: Kemp
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
mesh_terms: D000328:Adult; D000483:Alleles; D001724:Birth Weight / Q000235:genetics*; D001827:Body Height / Q000235:genetics*; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D056726:Genetic Association Studies; D006128:Growth / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020641:Polymorphism, Single Nucleotide