TY - JOUR

T1 - Genetics may affect the risk of undergoing surgery for rhizarthrosis

AU - Henkel, Cecilie

AU - Erikstrup, Christian

AU - Ostrowski, Sisse R.

AU - Pedersen, Ole B.

AU - Troelsen, Anders

AU - DBDS Genomic Consortium

N1 - Publisher Copyright: © 2023 Orthopaedic Research Society.

PY - 2024

Y1 - 2024

N2 - Osteoarthritis is a prevalent and severe disease. Involvement of the trapeziometacarpal joint is common and can lead to both pain and disability. Genetics are known to affect the risk of osteoarthritis, but it remains unclear how genetics affect disease trajectories. In this study, we investigated whether the genetic associations of trapeziometacarpal osteoarthritis (rhizarthrosis) vary with the need for surgical treatment. The study was conducted as a case-control genome-wide association study using individuals from the Copenhagen Hospital Biobank pain and degenerative musculoskeletal disease study and the Danish Blood Donor Study (N = 208,342). We identified patients diagnosed with rhizarthrosis and grouped them by treatment status, resulting in two case groups: surgical (N = 1083) and nonsurgical (N = 1888). The case groups were tested against osteoarthritis-free controls in two genome-wide association studies. We then compared variants suggestive of association (p < 10−6) in either of these analyses directly between the treatment groups (surgical vs. nonsurgical rhizarthrosis). We identified 10 variants suggestive of association with either surgical (seven variants) or nonsurgical (three variants) rhizarthrosis. None of the variants reached nominal significance in the opposite treatment group (p ≥ 0.14), and all 10 variants were significantly different between the treatment groups at a false discovery rate of 5%. These results suggest possible differences in the genetic associations of rhizarthrosis depending on surgical treatment. Clinical significance: Uncovering genetic differences between clinically distinct patient groups can reveal biological determinants of disease trajectories.

AB - Osteoarthritis is a prevalent and severe disease. Involvement of the trapeziometacarpal joint is common and can lead to both pain and disability. Genetics are known to affect the risk of osteoarthritis, but it remains unclear how genetics affect disease trajectories. In this study, we investigated whether the genetic associations of trapeziometacarpal osteoarthritis (rhizarthrosis) vary with the need for surgical treatment. The study was conducted as a case-control genome-wide association study using individuals from the Copenhagen Hospital Biobank pain and degenerative musculoskeletal disease study and the Danish Blood Donor Study (N = 208,342). We identified patients diagnosed with rhizarthrosis and grouped them by treatment status, resulting in two case groups: surgical (N = 1083) and nonsurgical (N = 1888). The case groups were tested against osteoarthritis-free controls in two genome-wide association studies. We then compared variants suggestive of association (p < 10−6) in either of these analyses directly between the treatment groups (surgical vs. nonsurgical rhizarthrosis). We identified 10 variants suggestive of association with either surgical (seven variants) or nonsurgical (three variants) rhizarthrosis. None of the variants reached nominal significance in the opposite treatment group (p ≥ 0.14), and all 10 variants were significantly different between the treatment groups at a false discovery rate of 5%. These results suggest possible differences in the genetic associations of rhizarthrosis depending on surgical treatment. Clinical significance: Uncovering genetic differences between clinically distinct patient groups can reveal biological determinants of disease trajectories.

KW - genetics

KW - GWAS

KW - rhizarthrosis

KW - surgery

KW - thumb

U2 - 10.1002/jor.25753

DO - 10.1002/jor.25753

M3 - Journal article

C2 - 38263870

AN - SCOPUS:85183054671

VL - 42

SP - 1001

EP - 1008

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 5

ER -