New genes at risk for osteoporosis are promising for a new treatment

Scientists have identified new risk genes for osteoporosis with the help of the latest data badysis tools.

Scientists have identified new risk genes for osteoporosis, the chronic bone loss that affects millions of people. Knowing the genes involved could later open the door to more effective treatments.

"Identifying the actual underlying cause of a disease often helps us to find targeted and correct treatments," said Struan F. A. Grant, Ph.D, study director, director of the study. Space and Functional Genomics Center (CSFG) to Philadelphia Children's Hospital (CHOP). "We have identified two new genes that affect the cells that form the bones and are involved in fractures and osteoporosis. In addition, the research methods we used could be applied more broadly to other diseases with a genetic component. "

The study identified two new genes, ING3 and EPDR1, which in turn has shown strong effects on human osteoblasts, a type of bone cell

Grant and his colleagues published their research in Nature Communications. He co-directed the study with Andrew D. Wells, PhD, immunology researcher at CHOP and the other director of the CSFG; and Kurt D. Hankenson, DMV, Ph.D., specialist in bone formation and remodeling at the University of Michigan. Grant and Wells are also faculty members of the Perelman School of Medicine at the University of Pennsylvania.

The research team investigated genetic loci, or regions of DNA, previously recognized as being badociated with bone mineral density in genome-wide badociation studies (GWAS), in the US. adult and at the child. "Scientists have known for some time that the gene closest to a variant badociated with a disease is not necessarily the cause of the disease," said Wells. Since GWAS research detects single-base DNA changes that are not typically found in obvious parts of the genome, many researches have turned to the broader context of interactions within the genome. of the genome – the entire complement of DNA in the cells.

Sometimes the modifications, called single nucleotide polymorphisms, or SNPs, present in GWAS are located near a responsible gene. Most often, the signal comes from a non-coding region of DNA that regulates another gene that can be found at thousands of bases of the DNA sequence. "The geography of the genome is not linear," Grant said. "Because DNA is folded into chromosomes, parts of the genome can come into physical contact, allowing key biological interactions that affect the way a gene is expressed. This is why we are studying the three-dimensional structure of the genome. "

By badyzing how chromatin, the fibers that make up chromosomes, are organized into specific forms, spatial genomics makes it possible to understand how genes interact physically with the regulatory regions of DNA that initiate transcription. Transcription is the process by which DNA is copied into RNA, the first event of gene expression.

The study identified two new genes, ING3 and EPDR1, which in turn has shown strong effects on human osteoblasts "Although we do not exclude other possible causative genes in these regions, ING3particularly noteworthy gene because we found that the genetic signal to this region was the the strongest badociated with bone density at the wrist – the main site of fracture in children, "said one of the authors.