The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature
ABSTRACT Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.
To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.
Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.
Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.
Full-textDOI: · Available from: Rosetta Chiavacci, May 20, 2015
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ABSTRACT: Adipocyte differentiation is key to determining the number of adipocytes during the development of obesity. Recent studies have shown that growth differentiation factor-5 (GDF5) promotes brown adipogenesis, however its role in white adipogenesis is still uncertain. The aim of the present study was to investigate the effect of GDF5 on white adipogenesis using 3T3-L1 preadipocyte model. In the present study, GDF5 was found to be differentially regulated during adipocyte differentiation. GDF5 protein increased the differentiation of 3T3-L1 preadipocytes, especially when these cells were exposed to hormone cocktails without insulin. During adipogenesis, GDF5 enhanced the expression of genes related to adipocyte differentiation and caused cells to enter the S phase. Short-hairpin-RNA knockdown of GDF5 in 3T3-L1 cells was found to prevent adipogenesis induced by a standard hormone cocktail and to downregulate the expression of adipocyte genes and proteins, this impairment could be partly rescued by GDF5 protein. Collectively, these results suggest that GDF5 can promote progression of the cell-cycle and increase numbers of cells in S phase, GDF5 might play a critical role in 3T3-L1 preadipocyte differentiation.Archives of Biochemistry and Biophysics 10/2014; DOI:10.1016/j.abb.2014.07.025 · 3.04 Impact Factor
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