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Biologics Feature

Source: Wikimedia Commons and Charlotte2222

Nine New Genes Associated With Osteoarthritis

Biloine W. Young • Mon, March 26th, 2018

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The most prevalent musculoskeletal disease and a leading cause of disability worldwide is osteoarthritis. There is, as yet, no truly disease modifying treatment for osteoarthritis.

Patients and doctors manage the disease with pain relievers and, ultimately, joint replacement surgery. Evidence suggests that patients with osteoarthritis fall into multiple phenotypic subgroups defined based on the main driver of disease.

To understand more about the genetic basis of osteoarthritis, Professor Eleftheria Zeggini and her colleagues from the Wellcome Sanger Institute studied 16.5 million DNA variations from the UK Biobank resource.

Following the combined analysis in up to 30,727 people with osteoarthritis and 297,191 people (the controls) who did not have osteoarthritis the team discovered nine new genes associated with this disease.

“Osteoarthritis is challenging to study because the disease can vary among people, and between the different joints affected, for example knee, hip, hand and spine,” Zeggini said.

“The discovery of these genes is positive news for the 8.5 million people in the UK living with osteoarthritis,” said Natalie Carter M.D., head of research liaison & evaluation at Arthritis Research UK. “By revealing how these genes contribute to osteoarthritis, this research could open the door for new treatments.”

“Using data from the UK Biobank resource, we have undertaken the largest genetic study of osteoarthritis to date and uncovered nine new genes associated with the disease.”

The researchers studied both normal cartilage and diseased cartilage from individuals who had a joint replacement.

According to the press release: “The team looked for genes that were active in the progression of the disease by extracting the relevant cells from healthy and diseased tissue, studying the levels of proteins in the tissue and sequencing the RNA—the messenger that carries instructions from DNA for controlling the production of proteins.”

Of the nine genes associated with osteoarthritis, the team identified five genes that differed significantly in their expression in healthy and diseased tissue.

“These results are an important step towards understanding the genetic causes of osteoarthritis and take us closer to uncovering the mechanism behind the disease,” said first author Eleni Zengini, from the University of Sheffield, UK, and Dromokaiteio Psychiatric Hospital, Greece. “Once we know that, it opens the door to developing new therapies for this debilitating disease.”

Type 2 Diabetes and Increased Lipid Levels NOT Causes of OA

“Using genetic data, we have shown that type 2 diabetes and increased blood lipid levels do not appear to be on the causal path to osteoarthritis,” said co-author Dr. Konstantinos Hatzikotoulas, from the Wellcome Sanger Institute. “We also reconfirmed that obesity is on the causal path to osteoarthritis.”

“Once we know that, it opens the door to developing new therapies for this debilitating disease,” said Ms. Zengini.

The scientists also explored genetic correlations between osteoarthritis and obesity, bone mineral density, type 2 diabetes, and raised blood lipid levels.

They applied a statistical technique known as causal inference analysis to uncover which traits and diseases cause osteoarthritis, and which do not.

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