Osteoarthritis

Osteoarthritis is the gradual breakdown of a joint — the cartilage first, then the bone and tissue around it — bringing pain, stiffness and loss of movement. It is the third most rapidly growing health condition associated with disability, after dementia and diabetes, and the number of people living with it is estimated to reach 1 billion by 2050. No treatment yet changes the course of the disease.

1,962,069 people, 962 associations

Hatzikotoulas et al. 2025, in Nature, combined genome-wide association studies of up to 489,975 people with osteoarthritis and 1,472,094 without. It established 962 independent associations, 513 of them not reported before. The study looked at osteoarthritis as a whole and joint by joint — hip, knee, hand, finger, thumb and spine — and separately at people whose hip or knee had been replaced.

Using gene activity, protein and epigenetic profiles from joint tissue itself, the authors named 700 effector genes: the genes most likely to be doing the work at those positions. 10% of them make a protein that an approved drug already targets. That is the practical point of the paper — a list of existing medicines that might be repurposed for a disease that has none of its own. Rare protein-altering variants in the effector genes had consistently larger effects than the common variants did.

What the genes have in common

The signal was concentrated in the pathways of embryonic skeletal development — the programmes that build the skeleton before birth. The study highlights eight biological processes in which several effector genes converge, among them the circadian clock, processes related to glial cells, the organisation of the extracellular matrix, and signalling pathways with an established role in osteoarthritis: TGFβ, FGF, WNT, BMP and retinoic acid.

62 positions, and where they were filed before

This catalogue holds 62 of the positions the study reports. Only 11 are filed on this site under osteoarthritis. The other 51 were already here under another trait — height, body weight, blood lipids, bone density — and the study reports the same positions for osteoarthritis.

Height is the clearest case. rs224333 in GDF5, a growth factor of the BMP family that helps form joints, is filed here under height; the study reports it for knee osteoarthritis. rs3817428 is a protein-altering variant in ACAN, the gene for aggrecan, a main structural molecule of cartilage. rs75621460 in TGFB1 and rs4073717 in FGF18 sit in two of the signalling families the study names. rs10832027 lies in BMAL1 (listed on this site as ARNTL), a core gene of the circadian clock. Three positions in FTO — rs1421085, rs1558902 and rs9941349 — are filed here under obesity, and body weight is an established risk for osteoarthritis. The abstract gives the number of effector genes, not their names, so this page does not say which of these genes are on that list.

One joint or several

Earlier, smaller studies are the basis of this site's pages on knee osteoarthritis and hip osteoarthritis. In this study's records some positions appear for more than one joint — rs75621460 is recorded for both hip and knee — and others for one only: rs11550348 in IRF2BP1 is recorded for the finger, and rs11588850 in SNAP47 for the thumb. The bones topic collects what this site holds on the skeleton.