Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966

Title: Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966
Author(s): Sovio, U
Bennett, AJ
Millwood, IY
Molitor, J
O'Reilly, PF
Timpson, NJ
Kaakinen, M
Laitinen, J
Haukka, J
Pillas, D
Tzoulaki, I
Molitor, J
Hoggart, C
Coin, LJM
Whittaker, J
Pouta, A
Hartikainen, A-L
Freimer, NB
Widen, E
Peltonen, L
Elliott, P
McCarthy, MI
Jarvelin, M-R
Item Type: Journal Article
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.
Publication Date: 6-Mar-2009
Date of Acceptance: 5-Feb-2009
URI: http://hdl.handle.net/10044/1/48219
DOI: https://dx.doi.org/10.1371/journal.pgen.1000409
ISSN: 1553-7390
Publisher: Public Library of Science
Journal / Book Title: PLOS Genetics
Volume: 5
Issue: 3
Copyright Statement: © 2009 Sovio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENETICS & HEREDITY
WIDE ASSOCIATION ANALYSIS
YOUNG MALE TWINS
CHILDHOOD
MODELS
HERITABILITY
VARIANTS
AGE
POPULATION
PUBERTY
STATURE
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
Humans
Body Height
Prospective Studies
Child Development
Genotype
Polymorphism, Single Nucleotide
Adolescent
Adult
Child
Infant, Newborn
European Continental Ancestry Group
Finland
Female
Male
Genome-Wide Association Study
Developmental Biology
0604 Genetics
Publication Status: Published
Article Number: ARTN e1000409
Appears in Collections:Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons