TY - JOUR
T1 - Genome-wide association meta-analysis of knee and hip osteoarthritis uncovers genetic differences between patients treated with joint replacement and patients without joint replacement
AU - DBDS Genomic Consortium
AU - Henkel, Cecilie
AU - Styrkársdóttir, Unnur
AU - Thorleifsson, Gudmar
AU - Stefánsdóttir, Lilja
AU - Björnsdóttir, Gyda
AU - Banasik, Karina
AU - Brunak, Søren
AU - Erikstrup, Christian
AU - Dinh, Khoa Manh
AU - Hansen, Thomas Folkmann
AU - Nielsen, Kaspar René
AU - Bruun, Mie Topholm
AU - Dowsett, Joseph
AU - Brodersen, Thorsten
AU - Thorgeirsson, Thorgeir E
AU - Gromov, Kirill
AU - Boesen, Mikael Ploug
AU - Ullum, Henrik
AU - Ostrowski, Sisse Rye
AU - Pedersen, Ole Birger
AU - Stefánsson, Kári
AU - Troelsen, Anders
N1 - © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
KW - Arthroplasty, Replacement, Hip
KW - Arthroplasty, Replacement, Knee
KW - Genome-Wide Association Study
KW - Humans
KW - Ion Channels
KW - Knee Joint/surgery
KW - Mechanotransduction, Cellular
KW - Osteoarthritis, Hip/genetics
KW - Osteoarthritis, Knee/genetics
KW - Pain
U2 - 10.1136/ard-2022-223199
DO - 10.1136/ard-2022-223199
M3 - Article
C2 - 36376028
SN - 0003-4967
VL - 82
SP - 384
EP - 392
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
IS - 3
ER -