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Chan et al. New insights into the genetics of human height: the value of SHR
DOI:10.1038/bonekey.2016.17
In order to investigate the influence of genetics on height, Chan et al. calculated the ratio of height when sitting to height when standing (sitting height ratio—SHR) in over 3500 African Americans and 21 590 Americans with European ancestry.
SHR has a large heritable component, with 39% of SHR differences explained by common genetic variants in African Americans and 26% in Europeans. Genome-wide significance for SHR association was achieved for six regions of the genome. These were found to overlap several candidate genes, including those encoding Insulin-like growth factor-binding protein 3 (IGFBP3) and T-box transcription factor (TBX2).
Subsequent pathway analyses revealed that the height loci that influence SHR, particularly those affecting leg length, are enriched within key biological candidate pathways such as bone/cartilage/growth plate pathways. Enrichment was also observed in gene sets involved in bone development (for example, those associated with abnormal rib morphology, chondrocyte differentiation, abnormal skeleton morphology, short tibia and short ribs) and in three cell/tissue types (cartilage, mesenchymal stem cells and osteoblasts).
Editor’s comment: The findings are not surprising, since adult height is a function of both upper- and lower-body size. Soranzo et al. assessed the contribution of height loci to the upper- (trunk) and lower-body (hip axis and femur) skeletal components of height. The ratio between leg length or spine/head length used by Chan et al. might be confounded by the soft tissue padding, since the sitting height depends on the volume of muscles of buttocks and thighs.
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