Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 22;15(1):2812.
doi: 10.1038/s41598-025-85871-w.

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127)

Qi Pan  1 , Yiwen Tao  1 , Tengda Cai  1 , Abi Veluchamy  2 , Harry L Hebert  2 , Peixi Zhu  3 , Mainul Haque  4 , Tania Dottorini  5 , Lesley A Colvin  2 , Blair H Smith  2 , Weihua Meng  6   7   8
Affiliations

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127)

Qi Pan et al. Sci Rep. .

Abstract

Hip pain is a common musculoskeletal complaint that leads many people to seek medical attention. We conducted a primary genome-wide association study (GWAS) on the hip pain phenotype within the UK Biobank cohort. Sex-stratified GWAS analysis approach was also performed to explore sex specific variants associated with hip pain. We found seven different loci associated with hip pain at GWAS significance level, with the most significant single nucleotide polymorphism (SNP) being rs77641763 within the EXD3 (p value = 2.20 × 10-13). We utilized summary statistics from the FinnGen cohort and a previous GWAS meta-analysis on hip osteoarthritis as replication cohorts. Four loci (rs509345, rs73581564, rs9597759, rs2018384) were replicated with a p value less than 0.05. Sex-stratified GWAS analyses revealed a unique locus within the CUL1 gene (rs4726995, p = 2.56 × 10-9) in males, and three unique loci in females: rs1651359966 on chromosome 7 (p = 1.15 × 10-8), rs552965738 on chromosome 9 (p = 2.72 × 10-8), and rs1978969 on chromosome 13 (p = 2.87 × 10-9). This study has identified seven genetic loci associated with hip pain. Sex-stratified analysis also revealed sex specific variants associated with hip pain in males and females. This study has provided a foundation for advancing research of hip pain and hip osteoarthritis.

Keywords: Genetic correlations; Genome-wide association study; Hip pain; Mendelian Randomization; PheWAS; Sex-stratified; UK Biobank.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Ethics Committee of the University of Nottingham Ningbo China.

Figures

Fig. 1
Fig. 1
The Manhattan plot of the GWAS analysis on hip pain (N = 221,127) The dashed red line indicates the cut-off p value of 5 × 10−8.
Fig. 2
Fig. 2
The regional plots of locus in EXD3 region.
Fig. 3
Fig. 3
The Manhattan plot of the male-specific GWAS analysis (N = 99,963) and the female-specific GWAS analysis (N = 121,164) on hip pain. The dashed red line indicates the cut-off p value of 5 × 10−8
Fig. 4
Fig. 4
Tissue expression results on 30 specific tissue types by GTEx in the FUMA. The dashed line shows the cut-off p value for significance with Bonferroni adjustment for multiple hypothesis testing
Fig. 5
Fig. 5
Tissue expression results on 53 specific tissue types by GTEx in the FUMA. The dashed line shows the cut-off p value for significance with Bonferroni adjustment for multiple hypothesis testing
Fig. 6
Fig. 6
Genetic correlation for pain intensity using LDSC on CTG-VL. For a full list see Supplementary Table 5.
See this image and copyright information in PMC

References

    1. Mills, E. S. et al. Current and Future Advanced Imaging Modalities for the Diagnosis of Early Osteoarthritis of the Hip. Orthop Res Rev14, 327–338. 10.2147/orr.S357498 (2022). - PMC - PubMed
    1. Elbrhamy, M. M., Farid, A. & Khater, H. M. Chronic non-traumatic hip pain in adults: the role of magnetic resonance imaging. Benha Medical Journal40, 100–113. 10.21608/bmfj.2022.143975.1607 (2023).
    1. Kim, C. & Carrier, D. P. Can iliopsoas bursitis be an early indicator of advancing hip osteoarthritis? International Journal of Case Reports in Orthopaedics (2022).
    1. Pianka, M. A., Serino, J., DeFroda, S. F. & Bodendorfer, B. M. Greater trochanteric pain syndrome: Evaluation and management of a wide spectrum of pathology. SAGE Open Med9, 20503121211022584. 10.1177/20503121211022582 (2021). - PMC - PubMed
    1. Christmas, C. et al. How common is hip pain among older adults? Results from the Third National Health and Nutrition Examination Survey. J Fam Pract51, 345–348 (2002). - PubMed

Publication types

LinkOut - more resources