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A new atlas of genetic effects on osteoporosis



To the left is a normal bone, and on the right there is an osteoporotic bone. Credit: International Foundation for Osteoporosis

The latest new study led by researchers at the Lada Davis Institute (LDI) at the Jewish General Hospital (JGH) has managed to compile an atlas of genetic factors associated with estimated bone mineral density (BMD), one of the most clinically most serious factors in diagnosing osteoporosis. Work, published in Nature Genetics, identifies 518 loci at the genome level, of which 301 are newly discovered, which explains 20% of the genetic variance associated with osteoporosis. Identifying many genetic factors provides great promise for the development of new targeted therapies for treating diseases and reducing fracture risk.

"Our findings are a significant advance in highlighting the potential for drug development," explains Dr Brent Richards, lead researcher, a LDI Center for Clinical Epidemiology that treats osteoporosis patients in her JGH practice. "This set of BMD-related genetic changes ensures drug targets that are likely to be useful for the prevention of osteoporotic fractures."

Osteoporosis is a very common age condition characterized by a progressive decrease in bone strength, resulting in high fracture risk. Particularly in elderly patients, fractures can have serious consequences, including the risk of mortality. Among all patients, fractures represent a major burden of hospitalization and prolonged rehabilitation. As the population ages, the urgency of improving preventive measures is becoming more and more intense.

"We currently have little treatment options," said Dr. Richards, a professor of medicine, human genetics and epidemiology and biostatistics at McGill University, "and many patients at high risk of fractures do not take current medication for fear of no matter what. It is always better to prevent than to treat. We can overwrite the bone injections, but they are overly expensive, we have medicines that prevent bone loss, but they have to be taken in strict order. The result is the number of people who need to be treated, but They are not, high We believe that we will have greater success in finding patients to follow the treatment regimen when it can be simplified.

This was the largest study ever conducted on the genetic determinants of osteoporosis, estimating more than 426,000 people in British Biobank. After analyzing the data, the researchers further improved their findings to isolate a set of genes that are highly enriched for known drug targets. This smaller set of target genes will allow drug makers to curb their quest for a solution to the clinical problem of fracture prevention in people who are predisposed to osteoporotic fractures. Animal models have already proven the validity of some of these genes.

"Although we have discovered many genetic factors associated with BMD, the kind of precise medicine that genetics offers should enable us to perfect those factors that can have the greatest effect on improving bone density and reduce the risk of fracture," says Dr. Morris, also from LDI and McGill University, the lead author of the study.


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More information:
Atlas of genetic effects on osteoporosis in humans and mice, Nature Genetics (2018). DOI: 10.1038 / s41588-018-0302-k, https: //vvv.nature.com/articles/s41588-018-0302-k

Reference of the journal:
Nature Genetics

Provides:
McGill University


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