Common genetic variation in eight genes of the <Emphasis Type="Italic">GH</Emphasis>/<Emphasis Type="Italic">IGF1</Emphasis> axis does not contribute to adult height variation |
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Authors: | Guillaume Lettre Johannah L Butler Kristin G Ardlie Joel N Hirschhorn |
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Institution: | (1) Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Seven Cambridge Center, Cambridge, MA 02142, USA;(2) Divisions of Endocrinology and Genetics, Program in Genomics, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA;(3) Genomics Collaborative/Seracare LifeSciences, Cambridge, MA, USA;(4) Biological Samples Platform, Broad Institute of Harvard and Massachusetts Institute of Technology, Seven Cambridge Center, Cambridge, MA 02142, USA;(5) Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA |
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Abstract: | Stature (adult height) is one of the most heritable human traits, yet few genes, if any, have been convincingly associated
with adult height variation in the general population. Here, we selected 150 tag SNPs from eight candidate genes in the growth
hormone (GH)/insulin-like growth factor-1 (IGF1) axis (GHR, GHRH, GHRHR, IGF1, IGFALS, IGFBP3, JAK2, STAT5B), and genotyped them in ∼2,200 individuals ascertained for short or tall stature. Nominally significant tag SNPs were then
tested in three additional replication cohorts, including a family-based panel to rule out spurious associations owing to
population stratification. Across the four height cohorts (N = 6,075 individuals), we did not observe any consistent associations between stature and common variants (≥5% minor allele
frequency) in these eight genes, including a common deletion of the growth hormone receptor gene exon 3. Tests of epistatic
interactions between these genes did not yield any results beyond those expected by chance. Although we have not tested all
genes in the GH/IGF1 axis, our results indicate that common variation in these GH/IGF1 axis genes is not a major determinant of stature, and suggest that if common variation contributes to adult height variation
in the general population, the variants are in other, possibly unanticipated genes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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