Genome-wide association study identifies a locus associated with rotator cuff injury

Roos, Thomas R.; Roos, Andrew K.; Avins, Andrew L.; Ahmed, Marwa A.; Kleimeyer, John P.; Fredericson, Michael; Ioannidis, John P. A.; Dragoo, Jason L.; Kim, Stuart K.

doi:10.1371/journal.pone.0189317

Cited by 29 publications

(38 citation statements)

References 43 publications

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“…While it is original for adjusting the data for population stratification (genetic ancestry and comorbidities) and for most of the studied SNP, this study presents some limitations. To our knowledge, only two studies evaluated a higher number of RCT patients . However, our investigation and most of the previously published report evaluated a small sample size for a genetic study.…”

Section: Discussionmentioning

confidence: 87%

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Figueiredo

Loyola

Belangero

et al. 2019

Journal Orthopaedic Research

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Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full‐thickness tears of the supraspinatus (Nfemales = 130; Nmales = 81) and 567 age‐matched controls (Nfemales = 317; Nmales = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co‐morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT‐genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192–201, 2020

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Section: Discussionmentioning

confidence: 87%

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Figueiredo

Loyola

Belangero

et al. 2019

Journal Orthopaedic Research

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“…Determination of genetic ancestry was performed by principal component analysis (PCA), as previously described [27]. These ancestry principal components were used in the GWAS to adjust for genetic ancestry.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequently, p-values were adjusted for λ in each population. Results from each population were combined by inverse-variance, fixed-effects meta-analysis as previously described [27]. SNPs that did not contain data for EUR were removed, because EUR comprises more than 80 % of the cohort.…”

Section: Genome-wide Association and Meta-analysismentioning

confidence: 99%

Two Genetic Variants Associated with Plantar Fascial Disorders

et al. 2018

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Plantar fascial disorder is comprised of plantar fasciitis and plantar fibromatosis. Plantar fasciitis is the most common cause of heel pain, especially for athletes involved in running and jumping sports. Plantar fibromatosis is a rare fibrous hyperproliferation of the deep connective tissue of the foot. To identify genetic loci associated with plantar fascial disorders, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 21,624 cases of plantar fascial disorders and 80,879 controls. One indel (chr5:118704153:D) and one SNP (rs62051384) showed an association with plantar fascial disorders at genome-wide significance (p<5×10) with small effects (odds ratios=0.93 and 1.07 per allele, respectively). The indel chr5:118704153:D is located within TNFAIP8 (encodes a protein induced by TNF alpha) and rs62051384 is located within WWP2 (which is involved in proteasomal degradation). These DNA variants may be informative in explaining why some individuals are at higher risk for plantar fascial disorders than others.

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“…A genome-wide association screen was performed for MCL injury using data from the genotyped Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort of the RPGEH. The data generation and data analysis pipeline have been previously described in Roos et al 2016 [26]. A complete description of the cohort and study design can be found in dbGaP (Study Accession: phs000674.…”

Section: Methodsmentioning

confidence: 99%

“…Determination of genetic ancestry was performed by principal component analysis (PCA), as previously described [26]. These ancestry principal components were used in the GWAS to adjust for genetic ancestry.…”

Section: Two Genetic Loci Associated With Medial Collateral Ligament mentioning

confidence: 99%

Two Genetic Loci associated with Medial Collateral Ligament Injury

et al. 2017

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Medial collateral ligament (MCL) injuries are a common knee injury, especially in competitive athletes. Identifying genetic loci associated with MCL injury could shed light on its etiology. A genome-wide association screen was performed using data from the Research Program in Genes, Environment and Health (RPGEH) including 1 572 cases of MCL injury and 100 931 controls. 2 SNPs (rs80351309 and rs6083471) showed an association with MCL injury at genome-wide significance (p<5×10) with moderate effects (odds ratios=2.12 and 1.57, respectively). For rs80351309, the genotypes were imputed with only moderate accuracy, so this SNP should be viewed with caution until its association with MCL injury can be validated. The SNPs rs80351309 and rs6083471 show a statistically significant association with MCL injury. It will be important to replicate this finding in future studies.

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Genome-wide association study identifies a locus associated with rotator cuff injury

Cited by 29 publications

References 43 publications

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

Two Genetic Variants Associated with Plantar Fascial Disorders

Two Genetic Loci associated with Medial Collateral Ligament Injury

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