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

Cecilie Henkel*, Unnur Styrkársdóttir, Gudmar Thorleifsson, Lilja Stefánsdóttir, Gyda Björnsdóttir, Karina Banasik, Søren Brunak, Christian Erikstrup, Khoa Manh Dinh, Thomas Folkmann Hansen, Kaspar René Nielsen, Mie Topholm Bruun, Joseph Dowsett, Thorsten Brodersen, Thorgeir E Thorgeirsson, Kirill Gromov, Mikael Ploug Boesen, Henrik Ullum, Sisse Rye Ostrowski, Ole Birger PedersenKári Stefánsson, Anders Troelsen, DBDS Genomic Consortium, Poul Jørgen Jennum (Medlem af forfattergruppering)

*Corresponding author af dette arbejde

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.

OriginalsprogEngelsk
Artikelnummer223199
TidsskriftAnnals of the Rheumatic Diseases
Vol/bind82
Udgave nummer3
Sider (fra-til)384-392
Antal sider9
ISSN0003-4967
DOI
StatusUdgivet - mar. 2023

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