Genome-wide association meta-analysis of knee and hip osteoarthritis uncovers genetic differences between patients... 2022 Henkel et al

Full title: Genome-wide association meta-analysis of knee and hip osteoarthritis uncovers genetic differences between patients treated with joint replacement and patients without joint replacement

Abstract

Objectives
Osteoarthritis is a common and severe, multifactorial disease with a well-established genetic component. However, little is known about how genetics affect disease progression, and thereby the need for joint placement. Therefore, we aimed to investigate whether the genetic associations of knee and hip osteoarthritis differ between patients treated with joint replacement and patients without joint replacement.

Methods
We included knee and hip osteoarthritis cases along with healthy controls, altogether counting >700 000 individuals. The cases were divided into two groups based on joint replacement status (surgical vs non-surgical) and included in four genome-wide association meta-analyses: surgical knee osteoarthritis (N = 22 525), non-surgical knee osteoarthritis (N = 38 626), surgical hip osteoarthritis (N = 20 221) and non-surgical hip osteoarthritis (N = 17 847). In addition, we tested for genetic correlation between the osteoarthritis groups and the pain phenotypes intervertebral disc disorder, dorsalgia, fibromyalgia, migraine and joint pain.

Results
We identified 52 sequence variants associated with knee osteoarthritis (surgical: 17, non-surgical: 3) or hip osteoarthritis (surgical: 34, non-surgical: 1). For the surgical phenotypes, we identified 10 novel variants, including genes involved in autophagy (rs2447606 in ATG7) and mechanotransduction (rs202127176 in PIEZO1). One variant, rs13107325 in SLC39A8, associated more strongly with non-surgical knee osteoarthritis than surgical knee osteoarthritis. For all other variants, significance and effect sizes were higher for the surgical phenotypes. In contrast, genetic correlations with pain phenotypes tended to be stronger in the non-surgical groups.

Conclusions
Our results indicate differences in genetic associations between knee and hip osteoarthritis depending on joint replacement status.

Paywall, https://ard.bmj.com/content/early/2022/11/14/ard-2022-223199

 

It is such a pity that people are still talking of osteoarthritis.

Osteoarthritis covers two quite different processes - articular cartilage wear and periarticular osteophyte formation. Established wear leads to osteophyte formation and osteophyte formation occurs as part of geometric changes that can lead to wear.

So it is unsurprising that 100 years ago the two processes were bundled into one diagnosis. But this the twenty-first century. Surgery is almost exclusively done when there is established wear. So 'non-surgical' cases are likely to have osteophytes but not so much wear, although not all.

(The situation is a bit like having a leaking roof and rotten beams. A leaky roof will lead to rotten beams and rotten beams will lead to a leaky roof so both are signs of a decaying building. But they are different problems.)

It would have been much more interesting to see how genes relate to the two different processes. The decisions on surgery must have been based on findings that would separate the two usefully - so it should not be hard to document them.