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

Sovio, Ulla, Bennett, Amanda J., Millwood, Iona Y., Molitor, John, O'Reilly, Paul F., Timpson, Nicholas J., Kaakinen, Marika, Laitinen, Jaana, Haukka, Jari, Pillas, Demetris, Tzoulaki, Ioanna, Molitor, Jassy, Hoggart, Clive, Coin, Lachlan J. M., Whittaker, John, Pouta, Anneli, Hartikainen, Anna-Liisa, Freimer, Nelson B., Widen, Elisabeth, Peltonen, Leena, Elliott, Paul, Mccarthy, Mark I. and Jarvelin, Marjo-Riitta (2009) Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. PLoS Genetics, 5 3: e1000409.1-e1000409.8. doi:10.1371/journal.pgen.1000409

Author Sovio, Ulla
Bennett, Amanda J.
Millwood, Iona Y.
Molitor, John
O'Reilly, Paul F.
Timpson, Nicholas J.
Kaakinen, Marika
Laitinen, Jaana
Haukka, Jari
Pillas, Demetris
Tzoulaki, Ioanna
Molitor, Jassy
Hoggart, Clive
Coin, Lachlan J. M.
Whittaker, John
Pouta, Anneli
Hartikainen, Anna-Liisa
Freimer, Nelson B.
Widen, Elisabeth
Peltonen, Leena
Elliott, Paul
Mccarthy, Mark I.
Jarvelin, Marjo-Riitta
Title Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1000409
Open Access Status DOI
Volume 5
Issue 3
Start page e1000409.1
End page e1000409.8
Total pages 8
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
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. Copyright:
Keyword Genetics & Heredity
Genetics & Heredity
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 104781
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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