Transcriptomic analysis of adhesive capsulitis of the shoulder

Kamal, Nima; McGee, Sean L.; Eng, Kevin; Brown, Graeme; Beattie, Sally; Collier, Fiona; Gill, Stephen D.; Page, Richard

doi:10.1002/jor.24686

Cited by 14 publications

(11 citation statements)

References 37 publications

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“…There are no gene expression associations in GTEX for rs28971325. However, a recent study found WNT7B was the second most differentially expressed transcript genome-wide with a log fold change of 7 ( p = 1x10 -16 ) in anterior capsule tissue from 22 patients undergoing arthroscopic capsulotomy surgery for frozen shoulder compared to 26 controls [ 28 ]. The lead SNP at the next strongest associated locus, rs1042704, is a missense variant in the MMP14 gene ( S6 Fig ).…”

Section: Resultsmentioning

confidence: 99%

“…GTEX analyses did not identify any strong eQTL’s with the lead SNP at the associated locus. However, a recent study performed RNA-seq on anterior capsule tissue from 22 patients undergoing arthroscopic capsulotomy surgery for adhesive capsulitis and compared to 26 undergoing arthroscopic stabilization surgery for a different condition [ 28 ]. WNT7B was the second most differentially expressed transcript genome-wide with a log fold change of 7 ( p = 1x10 -16 ), although it was noted that the expression levels of WNT7B was relatively low.…”

Section: Discussionmentioning

confidence: 99%

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A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor

et al. 2021

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Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16–1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren’s disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02–1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren’s disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor

et al. 2021

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“…There are no gene expression associations in GTEX for rs62228062. However, a recent study found WNT7B was the second most differentially expressed transcript genome-wide with a log fold change of 7 ( p= 1×10 −16 ) in anterior capsule tissue from 22 patients undergoing arthroscopic capsulotomy surgery for frozen shoulder compared to 26 controls [24].…”

Section: Resultsmentioning

confidence: 99%

“…GTEX analyses did not identify any strong eQTL’s with the lead SNP at the associated locus. However, a recent study performed RNA-seq on anterior capsule tissue from 22 patients undergoing arthroscopic capsulotomy surgery for adhesive capsulitis and compared to 26 undergoing arthroscopic stabilization surgery for a different condition [24]. WNT7B was the second most differentially expressed transcript genome-wide with a log fold change of 7 ( p= 1×10 −16 ), although it was noted that the expression levels of WNT7B was relatively low.…”

Section: Discussionmentioning

confidence: 99%

A genome wide association study of frozen shoulder identifies a common variant of WNT7B and diabetes as causal risk factors

Green

Jones

Evans

et al. 2020

Preprint

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Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes.We performed a genome wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 2064 cases identified from ICD-10 codes. We used data from FinnGen for replication. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder.We identified a single genome-wide significant locus (lead SNP rs62228062; OR=1.34 [1.28-1.41], p=2×10−16) that contained WNT7B. A recent transcriptome study identified WNT7B as amongst the most enriched transcripts in anterior capsule tissue in patients undergoing arthroscopic capsulotomy surgery for frozen shoulder suggesting WNT7B as a potential causal gene at the locus. The lead SNP was also strongly associated with Dupuytren’s contracture (OR=2.61 [2.50, 2.72], p<1×10−100). The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR=1.04 [1.02-1.07], p=6×10−5). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects.We have identified the first genetic variant associated with frozen shoulder. WNT7B is a potential causal gene at the locus. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.

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“…Studies that identify genetic associations with RCTs, as well as the molecular pathways that genes affect, play a key role in improving this understanding. 35 Surgical repair of RCTs is common following failed conservative treatment, yet retears occur in 25%-50% of patients within 12 months. 28 Thus, we require a refined method to predict and identify the candidates who will receive the greatest benefit from surgery.…”

mentioning

confidence: 99%

Polymorphisms and alterations in gene expression associated with rotator cuff tear and healing following surgical repair: a systematic review

Mousley

Hill-Buxton

Gill

et al. 2021

Journal of Shoulder and Elbow Surgery

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Background: Rotator cuff tears (RCTs) are a common cause of shoulder disability, yet both conservative and surgical treatment strategies can lead to poor results in some patient populations. Enhanced understanding of the genetic processes associated with RCTs can assist in the development of more effective management options and help predict individual responses to surgical treatment. This systematic review analyzes the current literature on the genetic footprint associated with RCTs and interprets these findings to enhance the current understanding of RCT pathogenesis, potential treatment regimens, and prognostic biomarkers of outcomes after surgical repair. Methods: A systematic search of the Embase, PubMed, and Web of Science electronic databases was performed. Medical Subject Headings (MeSH) and Emtree index terms were formulated from the concept terms ''rotator cuff tear,'' ''genetics,'' and ''human,'' and synonyms of these concepts were applied to the Web of Science search. Articles were screened against predefined inclusion and exclusion criteria. Eligible studies compared gene expression patterns and genetic polymorphisms between cases (with RCTs) and controls (without RCTs). Quality assessment was performed with studies being rated as high, moderate, or poor quality. A modified bestevidence synthesis was applied, and studies were determined to be of strong, moderate, or limited evidence. Results: The search identified 259 articles. Of these studies, 26 were eligible for review. Two studies were considered poor quality; 15 studies, moderate quality; and 9 studies, high quality. Analysis of these articles found that RCTs were associated with alterations in genes that code for the extracellular matrix, cell apoptosis, immune and inflammatory responses, and growth factor pathways. In particular, there was strong evidence of a significant association between RCTs and the genes MMP3, TNC, and ESRRB. Strong evidence of an association between BMP5 upregulation and successful healing after surgical repair was also found. Conclusion: This review provides strong evidence of an genetic association with RCTs. The genotype and gene expression patterns detailed within this review can assist in deciphering the biological mechanisms resulting in RCTs, as well as predicting an individual's Institutional review board approval was not required for this systematic review.

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Transcriptomic analysis of adhesive capsulitis of the shoulder

Cited by 14 publications

References 37 publications

A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor

A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor

A genome wide association study of frozen shoulder identifies a common variant of WNT7B and diabetes as causal risk factors

Polymorphisms and alterations in gene expression associated with rotator cuff tear and healing following surgical repair: a systematic review

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