Sheffield scientists have identified a clutch of nine genes linked to osteoarthritis, paving the way for new treatments.
They hope the discovery will aid the development of targeted drugs to combat the debilitating joint-eroding condition.
Currently there is no cure for osteoarthritis, which causes cartilage protecting the joints to break down resulting in swelling, pain, and loss of movement.
Injury, older age, inherited genes, obesity and certain occupations can all increase the risk of the disease.
Around 10 million people in the UK suffer from osteoarthritis, the leading cause of disability worldwide.
In the largest study of its kind, scientists studied 16.5 million DNA variations from the UK Biobank, a major storehouse of genetic and medical data provided for research by anonymous individuals.
Further analysis compared the DNA of 30,727 people with osteoarthritis and almost 300,000 without the condition.
The research, published in the journal Nature Genetics, uncovered nine new genes associated with the disease. Of these, five showed significant differences in activity in healthy and diseased tissue.
Professor Eleni Zengini, from the University of Sheffield, who co-led the study, said: "These results are an important step towards understanding the genetic causes of osteoarthritis and take us closer to uncovering the mechanism behind the disease.
"Once we know that, it opens the door to developing new therapies for this debilitating disease."
The findings also confirmed a causal connection between obesity and osteoarthritis, but ruled out links with Type 2 diabetes and high levels of blood fats.