Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/115969
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Type: Journal article
Title: Adult height variants affect birth length and growth rate in children
Author: Paternoster, L.
Howe, L.
Tilling, K.
Weedon, M.
Freathy, R.
Frayling, T.
Kemp, J.
Smith, G.
Timpson, N.
Ring, S.
Evans, D.
Lawlor, D.
Citation: Human Molecular Genetics, 2011; 20(20):4069-4075
Publisher: Oxford University Press
Issue Date: 2011
ISSN: 0964-6906
1460-2083
Statement of
Responsibility: 
Lavinia Paternoster, Laura D. Howe, Kate Tilling, Michael N. Weedon, Rachel M. Freathy, Timothy M. Frayling, John P. Kemp, George Davey Smith, Nicholas J. Timpson, Susan M. Ring, David M. Evans, Debbie A. Lawlor
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%).
Keywords: Alleles; adult; child; infant; parent; single nucleotide polymorphism; growth rate
Rights: © The Author 2011. Published by Oxford University Press This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
RMID: 0030043115
DOI: 10.1093/hmg/ddr309
Appears in Collections:Medicine publications

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