It's believed that inherited factors account for at least half of any individual's chance of developing this common condition that affects the joints, and understanding these factors could offer up new treatments.
The new study, published in The Lancet, compared the DNA of 7,400 osteoarthritis patients with that of 11,000 healthy volunteers in the UK.
This allowed the scientists to find the most promising "culprit" regions of the genetic code to study in more detail.
They repeated their work in another group of 7,500 people with osteoarthritis and about 43,000 individuals without the condition from Iceland, Estonia, the Netherlands, and the UK.
The results confirmed the three previously reported gene variants and found a further eight linked to osteoarthritis.
Further work is now needed to pinpoint the actual DNA changes within the genetic regions to establish exactly how these changes lead to osteoarthritis, the researchers said.
The one with the strongest effect was situated in the region of the GNL3 gene which produces a protein with an important role in cell maintenance. Three others were in DNA regions involved in the regulation of cartilage, bone development and body weight.
"We know that osteoarthritis runs in families and that this is due to the genes that people pass on, rather than their shared environment," Lead researcher John Loughlin of Newcastle University was quoted as saying by the BBC.
"In this study we were able to say with a high degree of confidence which genetic regions are the major risk factors for developing osteoarthritis: the first time that this has been possible for this common yet complex disease. It's an important first step."
Prof Alan Silman, medical director of Arthritis Research UK, said: "Until we understand the cause of this complex disease, we cannot hope to find a cure."
"This is a major breakthrough in our understanding of osteoarthritis, which we hope will help us to unlock the genetic basis of the disease," Prof Silman added.
