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New Genetic Risk Factors for Osteoarthritis Uncovered

Osteoarthritis is the most common form of arthritis. Some people call it degenerative joint disease or “wear and tear” arthritis and it occurs most frequently in the hands, hips, and knees. There are no curative treatments available and further understanding of disease cause is needed. Now, an international team of researchers led by Helmholtz Zentrum München report they have discovered new genetic risk factors for the disease and identified high-value drug targets.

Their findings are published in the journal Cell, Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.” The study is the largest study of osteoarthritis to date and may pave the way for new therapeutic developments and targets.

“Osteoarthritis affects over 300 million people worldwide,” the researchers wrote. “Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci.”

“This is a major step forward in understanding this debilitating disease and could not have been achieved without this international team effort,” explained Eleftheria Zeggini, PhD, director of the Institute of Translational Genomics at Helmholtz Zentrum München and professor at the Technical University of Munich.

The researchers say they have found genetic links between osteoarthritis and its main symptom, pain.

“Because we have investigated osteoarthritis in multiple joints, we have also identified specific genetic changes that underpin the risk for all forms of osteoarthritis. Some of these genes may prove to be validated as therapeutic targets for osteoarthritis, regardless of the joint affected,” said Cindy Boer, PhD, postdoc at Erasmus MC University Medical Center in the Netherlands, and co-first author of the article.

The researchers identified likely genes for osteoarthritis that constitute potential drug targets for the disease.

“Our findings have generated further knowledge on the differences between weight bearing and non-weight bearing joints and point to mechanisms that are common to disease development at any joint, and joint-type-specific. Indeed, bone and cartilage development pathways were enriched in signals traversing weight bearing and non-weight bearing joints, identifying joint development as a common mechanism for any form of osteoarthritis,” wrote the researchers.

“Our work provides a robust springboard for follow-up functional and clinical studies,” concluded the researchers. “We have demonstrated clear differences between distinct osteoarthritis patient populations, for example, based on disease severity, joint site affected, and sex. We enhance our understanding of the genetic etiology of disease, shed biological insights, and provide a stepping stone for translating genetic associations into osteoarthritis drug development, ultimately helping to catalyze an improvement in the lives of patients suffering from osteoarthritis.”

The post New Genetic Risk Factors for Osteoarthritis Uncovered appeared first on GEN – Genetic Engineering and Biotechnology News.

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