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Vitamin D Receptor Gene Polymorphisms Have Negligible Effect on Human Height

Published online by Cambridge University Press:  21 February 2012

Stuart Macgregor*
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Australia; Both authors contributed equally. Stuart.MacGregor@qimr.edu.au
Jouke-Jan Hottenga
Affiliation:
VU University, Biological Psychology, Amsterdam, the Netherlands; Both authors contributed equally.
Penelope A. Lind
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Australia.
H. Eka D. Suchiman
Affiliation:
LUMC University, Molecular Epidemiology, Einthovenweg, Leiden, the Netherlands.
Gonneke Willemsen
Affiliation:
VU University, Biological Psychology, Amsterdam, the Netherlands.
P. Eline Slagboom
Affiliation:
LUMC University, Molecular Epidemiology, Einthovenweg, Leiden, the Netherlands.
Grant W. Montgomery
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Australia.
Nicholas G. Martin
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Australia.
Peter M. Visscher
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Australia.
Dorret I. Boomsma
Affiliation:
VU University, Biological Psychology, Amsterdam, the Netherlands.
*Corresponding
*Address for correspondence: Stuart Macgregor, Genetic Epidemiology, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Australia, 4029.

Abstract

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Human height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (BsmI) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [FokI] and rs7139166 [-1521] polymorphisms). We genotyped large Caucasian samples from Australia (N = 3906) and the Netherlands (N = 1689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3cm) to the effect observed in the published adult meta-analysis. An effect of this size explains ~0.1% of the phenotypic variance in height — this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height.

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