Epidemiological evidence has suggested that there is an association between osteoporosis and type 2 diabetes mellitus (T2DM); however, the mechanisms underlying this association have been unclear. Now, new research has identified genetic variants that could account for the link between osteoporosis and T2DM.

“An important task and challenge is to perform a systematic search for shared genetic loci influencing these two diseases,” explains Hong-Wen Deng. “We applied the pleiotropic conditional false discovery rate (cFDR) method to two sets of data from genome-wide association studies to identify novel variants with pleiotropic effects on femoral BMD and T2DM.” The analysis included 53,236 participants with data on femoral neck BMD and 159,208 participants with data on T2DM.

The researchers identified 27 SNPs associated with femoral neck BMD and 61 SNPs associated with T2DM. Of these SNPs, four were shared between femoral neck BMD and T2DM, indicating that they could be pleiotropic. One of these SNPs was located in PLEKHA1; further analysis revealed that this gene is differentially expressed between patients with high versus low BMD and between patients with or without T2DM. Weighted gene co-expression analyses also showed that PLEKHA1 is associated with multiple genes that are known to be involved in osteoporosis or T2DM.

“Our study highlights PLEKHA1 as an important potentially pleiotropic gene,” says Deng. PLEKHA1 is involved in regulating phosphorylation, which in turn regulates a range of cellular processes, including insulin sensitivity and bone mineralization. “Therefore, PLEKHA1 might participate in bone and T2DM metabolism,” concludes Deng. The researchers hope that future studies will build on these findings, including exploring the role of PLEKHA1 in osteoporosis and T2DM in more detail. The authors also note that their findings need to be validated.