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

Authors: Leena Peltonen; Leena Peltonen; Clive J. Hoggart; Anna-Liisa Hartikainen; Jari Haukka; Jassy Molitor; Marjo-Riitta Järvelin; +18 Authors

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

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.

Keywords

Male, European Continental Ancestry Group/*genetics, CHILDHOOD, VARIANTS, QH426-470, 1105 Ecology, *Body Height, Child Development, 1306 Cancer Research, Prospective Studies, GENETICS & HEREDITY, Child, POPULATION, Finland, Pediatric, Genetics & Heredity, HERITABILITY, Single Nucleotide, Female, Life Sciences & Biomedicine, Research Article, Adult, 2716 Genetics (clinical), *Child Development, STATURE, Adolescent, Genotype, Evolution, MODELS, European Continental Ancestry Group, 610, Polymorphism, Single Nucleotide, White People, AGE, Behavior and Systematics, 1311 Genetics, Clinical Research, 1312 Molecular Biology, Genetics, Humans, Polymorphism, 0604 Genetics, Science & Technology, Human Genome, YOUNG MALE TWINS, Infant, Newborn, Infant, Newborn, Body Height, WIDE ASSOCIATION ANALYSIS, PUBERTY, Developmental Biology, Genome-Wide Association Study

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
141
Top 10%
Top 10%
Top 1%
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