Found! Gene Responsible for BMD and Fracture Risk!

Genetic wizards from Hebrew SeniorLife Institute for Aging Research (IFAR), a Harvard-affiliated institution, worked with scientists from a number of international institutes to identify a genetic variant regulating a gene responsible for bone mineral density and fracture risk. Findings from this study—funded in part by grants from the National Institutes of Health (NIH)—are published in the journal Nature.

“Our study explores the hereditary aspect of osteoporosis by investigating the role our genes play in determining bone mineral density and who is at risk of fracture due to low bone density, ” explains senior author Douglas Kiel, M.D., M.P.H., Director of the Musculoskeletal Research Center at IFAR, Hebrew SeniorLife in Boston, Professor of Medicine, Harvard Medical School and Associate Member of the Broad Institute of Harvard and MIT, in the September 15, 2015 news release. “Understanding the genomics underlying skeletal fragility (osteoporosis) may lead to preventative interventions that ultimately reduce fractures as we age.”

As indicated in the news release, “For the present study, the research team sequenced the entire genome of more than 2, 800 people and combined this with exome sequencing as well as another 3, 500 people with “deep imputation” of their genotyping results, which is a way to fill in information about the unanalyzed portions of the genome by incorporating the data coming from the 2, 800 people with sequencing of their genomes. The results confirmed that some of the genetic variants were associated with bone mineral density by comparing their data with information from more than 20, 000 other research participants. The investigators then looked at data from many other studies (totaling more than half-a-million people) and determined that some of these variants also influenced a person’s risk of breaking a bone.”

“Study results show that a gene involved at the earliest stages of human development, the engrailed homeobox-1 gene, plays a central role in regulating bone density. This is the first time that researchers have connected the gene’s product, the protein EN1, to bone biology in adults. Furthermore, this study validates the use of whole-genome, sequencing-based discovery and deep imputation as sound methods for identifying novel genetic associations.”

Dr. Kiel noted, “Our findings enhance understanding of the genetics underlying the development of osteoporosis. Ideally, genomic research will one day lead to more personalized interventions (precision medicine) that, in this case, will reduce bone loss and prevent fractures in older adults.”

Dr. Kiel told OTW, “The goal of studies like these is to discover potentially new pathways that may be used to develop new treatments for osteoporosis. The next step would therefore be to better characterize the protein produced by the EN1 gene and to determine if molecules can be developed to favorably influence this pathway to increase bone strength. At this stage, orthopedic surgeons will not be able to apply any of the findings to clinical practice. It is too early in the research pipeline.”