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Wang et al. Phenome-wide association study reveals novel genes that impact BMD
DOI:10.1038/bonekey.2016.54
Wang et al. performed a comparative analysis of the murine BXD phenome with a clinically relevant human resource (BioVU) that is used to study phenotype-genotype associations. A total of 5 million sequence variants from the murine population was compared with gene variants from the human cohort.
The murine phenome, which is open access, consists of approximately 4,500 physiological, metabolic, behavioral and pharmacological traits and is the largest coherent phenome available. The novel matched analysis of gene variants revealed several previously unrecognized associations, including 21 missense mutations within the gene Col6a5, which were linked to variability in bone mineral density in both mice and humans.
Detailed analysis showed that one single nucleotide polymorphism within exon 3 of COL6A5 in humans is associated with osteopenia and other bone/cartilage abnormalities, as well as respiratory disorders and giant cellarteritis.
Editor’s comment: Quantitative micro-CT analysis confirms a marked difference in femoral cortical BMD between B6 and D2 parents with the polymorphic Col6a5 gene. Phenome-wide association analysis is thus a powerful research tool that is complimentary to the genome-wide association study.
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