bone disorders

14 Novel Osteoporosis-Related Genes Are Identified

Researchers have identified 14 novel candidate genes that appear to be implicated in osteoporosis.

“Though genome-wide association studies have identified hundreds of genetic variants associated with osteoporosis-related traits, such as bone mineral density and fracture, it remains a challenge to interpret their biological functions and underlying biological mechanisms,” the researchers wrote.

To identify novel candidate genes linked with osteoporosis, the researchers integrated data on diverse expression quantitative trait loci and splicing quantitative trait loci with powerful datasets from genome-wide association studies.

“[W]e conducted a transcriptome-wide association study for total body bone mineral density (n=66,628 for discovery and 7697 for validation) and fracture (53,184 fracture cases and 373,611 controls for discovery and 37,857 cases and 227,116 controls for validation), respectively,” they explained.

The investigation revealed 88 genes significantly linked with total body bone mineral density and fracture via gene expression or ribonucleic acid splicing. Some 78 of the genes have potential causal effects on total body bone mineral density and fracture in at least one specific tissue, according to the study. That includes 64 genes, such as inhibitor of growth family member 3 (ING3), cadherin like and PC-esterase domain containing 1 (CPED1), and Wnt family member 16 (WNT16), identified in previous studies.

Among the 14 novel genes found in the current study are:

  • DBF4 zinc finger B (DBF4B),
  • Granulin precursor (GRN),
  • Transmembrane and ubiquitin like domain containing 2 (TMUB2), and
  • Unc-93 homolog B1, TLR signaling regulator (UNC93B1).


“Overall, our findings provide novel insights into the pathogenesis mechanisms of osteoporosis and highlight the power of a transcriptome-wide association studies to identify and prioritize potential causal genes,” the researchers concluded.

—Jolynn Tumolo


Liu Y, Shen H, Greenbaum J, et al. Gene expression and RNA splicing imputation identifies novel candidate genes associated with osteoporosis. J Clin Endocrinol Metab. 2020;105(12):dgaa572.