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7 pleiotropic genes associated with osteoporosis, obesity

02 Feb 2018
Scientists are keen on revisiting tough-to-sequence regions that frequently have important genes.

There appears to be seven potentially pleiotropic genes linked to obesity and osteoporosis, a recent study has shown.

These potentially pleiotropic loci associated with obesity and osteoporosis included rs3759579 (MARK3), rs2178950 (TRPS1), rs1473 (PUM1), rs9825174 (XXYLT1), rs2047937 (ZNF423), rs17277372 (DNM3) and rs335170 (PRDM6). Of these, the PUM1 gene was found to be differentially expressed in osteoporosis-related cells (B lymphocytes) and obesity-related cells (adipocytes).

In weighted genes coexpression network analysis (WGCNA), PUM1 showed positive interaction with several known osteoporosis genes, such as AKAP11, JAG1 and SPTBN1. Moreover, ZNF423 gene was the highly connected intramodular hub gene and interconnected with 21 know osteoporosis-related genes, including JAG1, EN1 and FAM3C.

“The[se] findings may provide new insights into a potential genetic determination and codetermination mechanism of osteoporosis and obesity,” researchers said.

To identify novel pleiotropic genes associated with osteoporosis and obesity, researchers applied a pleiotropic conditional false discovery rate method to three independent genome-wide association studies (GWASs) summary statistics of femoral neck bone mineral density (BMD), body mass index and waist-to-hip ratio.

Subsequently, they conducted differential expression analysis for the potentially pleiotropic genes, as well as WGCNA to identify functional connections between the suggested pleiotropic genes and known osteoporosis/obesity genes using transcriptomic expression datasets in osteoporosis/obesity-related cells.

In a recent review, researchers claimed that genetic discovery is “effective in the unbiased identification of novel drug targets” and that “GWASs have begun to provide insight into genetic basis of osteoporosis.” In addition, “GWASs have led to the identification of [approximately] 100 loci associated with BMD and other bone traits related to risk of fracture” over the last decade. [Transl Res 2017;181:15-26]

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