Osteoarthritis is the most prevalent musculoskeletal disease and a leading cause of disability worldwide.
There is no treatment for osteoarthritis; the disease is managed with pain relief and culminates in joint replacement surgery.
To understand more about the genetic basis of osteoarthritis, Wellcome Sanger Institute’s Professor Eleftheria Zeggini and co-authors studied 16.5 million DNA variations from the UK Biobank resource.
Following combined analysis in up to 30,727 people with osteoarthritis and 297,191 people without osteoarthritis in total (controls), the team discovered nine new genes that were associated with this disease.
“Osteoarthritis is challenging to study because the disease can vary among people, and also between the different joints affected, for example knee, hip, hand and spine,” Professor Zeggini said.
“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 discovery of these genes is positive news for the 8.5 million people in the UK living with osteoarthritis,” said Dr. Natalie Carter, head of research liaison & evaluation at Arthritis Research UK, who was not involved in the study.
“People living with this debilitating condition currently have limited treatment options. Meanwhile, they can struggle to do the day-to-day things most of us take for granted, like going to work or getting dressed independently.”
“By revealing how these genes contribute to osteoarthritis, this research could open the door for new treatments to help millions of people live the pain free life they deserve.”
The researchers then investigated the role of the nine new genes in osteoarthritis, by studying both normal cartilage and diseased cartilage from individuals who had a joint replacement.
They 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 in particular 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.”
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.
Within the limits of their study, they discovered that type 2 diabetes and high levels of lipids in the blood do not have causal effects on osteoarthritis, but reaffirm that obesity does.
“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.”
Source: sci-news.com