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Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.

Sovio, U; Bennett, AJ; Millwood, IY; Molitor, J; O'Reilly, PF; Timpson, NJ; Kaakinen, M; ... Jarvelin, MR; + view all (2009) Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. PLoS Genet , 5 (3) , Article e1000409. 10.1371/journal.pgen.1000409. Green open access

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Abstract

Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth.

Type: Article
Title: Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1000409
Publisher version: http://dx.doi.org/10.1371/journal.pgen.1000409
Language: English
Additional information: © 2009 Sovio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Financial support was received from the Academy of Finland (project grants 104781, 120315 and Center of Excellence in Complex Disease Genetics), University Hospital Oulu, Biocenter, University of Oulu, Finland, NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), ENGAGE project and grant agreement HEALTH-F4-2007-201413, the Medical Research Council (studentship grant G0500539, centre grant G0600705), the Wellcome Trust (project grant GR069224), UK, and the Research Council UK fellowship. The DNA extractions, sample quality controls, biobank up-keeping and aliquotting was performed in the national Public Health Institute, Biomedicum Helsinki, Finland and supported financially by the Academy of Finland and Biocentrum Helsinki. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Adolescent, Adult, Body Height, Child, Child Development, European Continental Ancestry Group, Female, Finland, Genome-Wide Association Study, Genotype, Humans, Infant, Newborn, Male, Polymorphism, Single Nucleotide, Prospective Studies
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1389825
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