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The correlation between strain rates and the mechanical properties of HTPB propellant with 90% solid content (mass fraction) was investigated by uniaxial tensile tests at different tensile rates, and the tensile fracture surface was observed by scanning electron microscope (SEM). The effects of strain rate on the mechanical properties and failure mechanisms of the propellant were analyzed. The results show that the stress--strain curve of the propellant appears an arc segment phenomenon at low tensile rates. With the increase of tensile rates, the stress--strain curves of propellant gradually changes from 5 segment to 4 segment. The initial modulus and the maximum tensile strength of the propellant show an increasing trend with an increase in the tensile rates. The maximum elongation of the propellant decreases with an increase in the strain rate, and the maximum elongation of propellant is only 33.9% when the strain rate is 1 190.48 X 10 4s 1 . With the increase of strain rate, the failure mechanism of propellant gradually changes from particle dehumidification to matrix tearing, without particle fragmentation. [ABSTRACT FROM AUTHOR]

The Line laser gear measuring center (LLGMC) is an innovative gear measurement equipment that offers high efficiency but low accuracy. One crucial factor that influences its measurement accuracy is the presence of geometric errors. In this study, we conducted a thorough analysis of these geometric errors and proposed a method for modeling spatial errors. Instead of directly considering the geometric errors, we replaced them with the installation errors of the gear and line laser probe. This approach simplifies and improves the error transmission relationship. Subsequently, the installation errors are converted into a unified representation of the height error of the incident light from the line laser. A spatial error model that considers nine installation errors is then further established. By numerically calculating the sensitivity of different error sources, we effectively identified the errors that have a significant impact on the accuracy of LLGMC. Moreover, accuracy distribution is carried out to ensure that LLGMC can meet the measurement accuracy requirements for gears with a tolerance class of 6. This article provides a theoretical foundation for the structural design and accuracy assurance of LLGMC during the research and development phase. [ABSTRACT FROM AUTHOR]

Self‐trapped excitons (STEs), proved to be the major source of white‐light emission in 2D metal halide perovskites (MHPs) van der Waals (vdW) heterostructures, have aroused intense interest in photovoltaic and photoelectric applications. Nevertheless, the intrinsic mechanisms of STEs in these vdW heterostructures are still ambiguous. Herein, the binding energy correction ΔEB of a STE stemming from the exciton–phonon coupling in MHPs vdW heterostructures based on the Pollmann–Büttner model is studied. It is found that there are two types of STEs with ΔEB>0 and ΔEB<0. The corresponding nuclear coordinate diagrams are given to explain the differences between them and why the STEs with ΔEB<0 are hard to be observed in experiments. The phase transition between two types of STEs can be achieved by regulating the structural parameters, such as the vertical distance between the encapsulation layers, the position of the monolayer MHP in the heterostructure as well as replacing the encapsulation materials. The theoretical results provide important insights into the analysis and modulation of STEs in 2D vdW heterostructures. [ABSTRACT FROM AUTHOR]

In this paper, a comprehensive theory for wavelength modulation laser heterodyne spectroscopy is presented. Some necessary simplifications based on the Taylor series are introduced, the general formulas employed to demodulate the first harmonic signal (1f), the second harmonic signal (2f), and higher harmonic signal (nf) are derived in details, and hence the formulas are suitable for an arbitrary intensity modulation amplitude and modulation index. The purpose of this paper: an overview of how the laser heterodyne harmonic signal depends on the experimental parameters of intensity modulation amplitude and modulation index is reported. This overview is helpful to choose these parameters for the best laser heterodyne harmonic signal because it initiated a new pathway for systematically analyzing the relationships between the experimental parameters and the laser heterodyne harmonic signal. [ABSTRACT FROM AUTHOR]

Background: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated. Methods: In this study, the reliability of UUO-induced renal interstitial fibrosis was evaluated by histopathological verification. High-throughput transcriptome sequencing was used to elucidate the molecular mechanism of hirudin, differentially expressed mRNAs were identified, and their functions were analyzed by GO analysis and GSEA. In addition, the RNA-seq results were validated by in vitro and vivo experiments. Results: We found 322 identical differential expressed genes (IDEs) in the UUO hirudin-treated group compared with the sham group. Functional enrichment analysis indicated that cellular amino acid metabolic processes were the most obvious enrichment pathways in biological processes. In terms of molecular functional enrichment analysis, IDEs were mainly enriched in coenzyme binding, pyridoxal phosphate binding and other pathways. In addition, microbody is the most obvious pathway for cellular components. A total of 115 signaling pathways were enriched, and AMPK, JAK-STAT, and PI3K-Akt signaling pathways were the important signaling pathways enriched. We found that PI3K, p-Akt, and mTOR expression were significantly reduced by hirudin treatment. In particular, our results showed that hirudin could induce a decrease in the expression of autophagy-related proteins such as P62, LC3, Beclin-1 in TGF-β1-induced NRK-52E cells. Conclusion: Our results suggest that hirudin may protect the kidney by ameliorating renal autophagy impairment through modulating the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the potential mechanism underlying the involvement of CB2 in osteoporosis. Micro‐CT was utilized to examine femur bone architecture. Also, real‐time PCR and Western blot analysis were utilized to detect the effect of 2‐AG on the expression of CB2 and Notch, or the interaction between CB2 and Notch 2. 2‐AG treatment up‐regulated BMD, Tb.Sp and SMI in OVX mice, whereas proportion of bone volume in total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) were decreased in 2‐AG‐treated OVX mice. Accordingly, 2‐AG administration up‐regulated Notch 1 expression in OVX mice but had no effect on CB2 and Notch 2 expression. Meanwhile, 2‐AG administration promoted the differentiation of hBMSCs in OVX mice, while exhibiting no effect on the proliferation of hBMSCs. Furthermore, in the cellular models, 2‐AG treatment also up‐regulated Notch 1 expression but had no effect on CB2 and Notch 2 expression, while Notch 1 shRNA had no effect on CB2 and Notch 2 expression. 2‐AG promoted cell proliferation and differentiation, which were inhibited by Notch 1 shRNA. NICD had no effect on CB2 level but increased Notch 1 expression, and CB2 shRNA decreased CB2 and Notch 1 expression. Finally, CB2 shRNA inhibited cell proliferation and differentiation, whereas NICD promoted proliferation and differentiation of hBMSCs. Our results provided further evidence for the association of CB2 gene with BMD and osteoporosis, and identified CB2 as a promising target for the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. Methods: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. Results: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44–1.82 in HFHD, 0.79–1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. Conclusion: Hospitalization rates and AAC were observed to be equal for HDF and HFHD. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN.Methods: We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks.Discussion: This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN.Trial Registration: ClinicalTrials.gov, identifier: NCT02231125 . Registered on 30 August 2014. [ABSTRACT FROM AUTHOR]

Backgroud: Zicuiyin (ZCY) decoction created by Xichun Zhang in the Qing dynasty has been used on diabetes mellitus and complications for more than two centuries in China. Huangkui capsule (HKC) is a listed Chinese patent medicine to treat diabetic kidney disease (DKD). To determine whether ZCY is non-inferior to HKC in the treatment of DKD, a multicenter, parallel-control, open-label, randomized clinical trial was conducted.Methods: In this clinical trial, 88 DKD patients were recruited at three centers in Tianjin from January 2018 to December 2019. They were randomized to receive HKC (2.5 g, TID) or ZCY (crude drug amount 75 g, 150 ml, BID) for eight weeks based on routine treatment. The primary outcome was the change of estimated glomerular filtration rate (eGFR). The secondary outcomes included change of serum creatinine (SCr), urinary albumin excretion rate, 24 h urinary protein, urinary albumin-creatinine ratio, glycosylated hemoglobin A1c, symptom scores, and microbiota compositions profiles.Results: The change of eGFR in HKC and ZCY groups were -7.08 ± 24.65 and 2.57 ± 18.49 ml/min/1.73 m2, respectively (p < 0.05). The 95% lower confidence limit for the difference between the estimated means was 1.93 ml/min/1.73 m2, establishing the superiority of ZCY. Compared to HKC, ZCY could significantly decrease SCr and symptom scores (p < 0.05). There were no significant differences in other outcomes between the two groups (p > 0.05). ZCY ameliorated gut microbiota dysbiosis, including increased Prevotellaceae and Lactobacillaceae and decreased Enterobacteriales, Clostridiaceae and Micrococcaceae. No severe adverse events were reported in any group.Conclusions: ZCY had better efficacy in improving and protecting kidney function. It would be an alternative option to treat DKD, especially those who decline eGFR and gut microbiota dysbiosis.Trial Registration: Chinese Clinical Trial Registry: ChiCTR-OON-17012076. Registered July 21, 2017. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is a common disease. Most chronic kidney diseases evolve from primary glomerulonephritis. Proteinuria is an independent risk factor for the progression of chronic kidney disease. The general consensus is that therapy administered to decrease proteinuria should include steroids and/or immunosuppressants, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. However, the side effects of, and adverse reactions to, these agents reduce the benefits to patients. In addition, the cost of these drugs is relatively high. Therefore, identification of inexpensive and effective drugs to decrease proteinuria is urgently needed. Shenyankangfu tablets have been a widely applied Chinese patent medicine for many years to decrease proteinuria. However, there is a lack of research-derived data regarding the clinical use. Therefore, we designed the present randomized controlled clinical trial to compare the efficacy and safety of Shenyankangfu tablets versus losartan potassium for control of proteinuria in patients with primary glomerulonephritis.Methods/design: This study will be a multicenter, prospective, double-blind, double-dummy, randomized controlled clinical trial. We will enroll 720 patients diagnosed with primary glomerulonephritis. The eligible patients will be randomly divided into the following groups at a 1:1:1:1:1 ratio: Shenyankangfu tablets group, losartan potassium 50 mg group, losartan potassium 100 mg group, Shenyankangfu tablets + losartan potassium 50 mg group, and Shenyankangfu tablets + losartan potassium 100 mg group. All groups will be followed up for 48 weeks; follow-up visits will be performed, at weeks 0, 4, 8, 12, 24, 36, and 48. The primary efficacy outcome will be the post-treatment change in the 24-hour proteinuria level, and the secondary efficacy outcomes will be the post-treatment changes in the serum creatinine level, estimated glomerular filtration rate, traditional Chinese medicine syndrome score, and serum albumin level.Discussion: The results of this trial will provide solid data for use in evidence-based medicine with respect to the efficacy and safety of Shenyankangfu tablets for control of proteinuria in patients with primary glomerulonephritis compared to those of losartan potassium. Moreover, we infer that therapy comprising Shenyankangfu tablets + losartan potassium can decrease proteinuria to a larger extent than Shenyankangfu tablets or losartan potassium can alone.Trial Registration: This trial was registered on 12 February 2014 at ClinicalTrials.gov (ID number NCT02063100). [ABSTRACT FROM AUTHOR]

• In this work, a novel augmented 4*4 matrix model for the slightly misaligned optical multi-pass cell is proposed. • The augmented 4*4 matrix is proposed to describe the behavior of light rays in the misaligned optical multi-pass cell. • The augmented 4*4 matrix can be used to analyze the misalignment sensitivity of the optical multi-pass cell. A novel augmented 4*4 matrix model for the slightly misaligned optical multi-pass cell whose spherical mirrors are not coaxial due to the presence of small misaligned angle and linear displacement of the spherical mirrors is reported. The augmented 4*4 matrix model is proposed to describe the behavior of light rays in the misaligned optical multi-pass cell. By augmented 4*4 matrix model, a series of numerical calculation are performed to validate that the incident light ray remains unchanged, and then retrace the same spot pattern. It is found that the set of spot patterns from numerical analysis displays a displacement on the surface of the mirror and the misaligned optical elements increase the loss and reduce pass counts. More importantly, the augmented 4*4 matrix model can be used to analyze the misalignment sensitivity of the optical multi-pass cells. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population.In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated.We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69–0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61–0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63–0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren–Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46–0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6–0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001).These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.Key Point• Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA. [ABSTRACT FROM AUTHOR]