Attempt to replicate published genetic associations in a large, well-defined osteoarthritis case–control population (the GOAL study)

Limer, K.L.; Tosh, Kerrie; Bujac, Sarah R.; McConnell, Ryan; Doherty, Sally; Nyberg, Fredrik; Zhang, Weiya; Doherty, Michael; Muir, Kenneth; Maciewicz, Rose A.

doi:10.1016/j.joca.2008.09.019

Cited by 41 publications

(40 citation statements)

References 31 publications

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“…Further, certain association between rs3740199 SNP in the ADAM12 gene and radiographic knee OA or presence of osteophytes in TFJ was observed in a Chingford Study cohort study (women aged 47-63 years, N = 749), but this association was failed to replicate in GOAL study (1,040 cases with clinical knee OA from orthopaedic surgery lists, Nottingham, UK) [8]. However, our previous work showed that the rs3740199 ADAM12 gene was linked to the presence of osteophytes of both joints in the whole investigated group and to OA in the PFJ in men [7].…”

Section: Discussionmentioning

confidence: 99%

“…ADAM12 has been shown to be implicated in a variety of human diseases, such as Down's syndrome [3], breast, bladder, liver and lung cancers [4], as well as cardiac hypertrophy [5]. ADAM12 gene has also been observed to be associated with the development of knee osteoarthritis (OA) [6,7], but a recent study was unable to replicate this association [8].…”

Section: Introductionmentioning

confidence: 99%

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Association of ADAM12-S protein with radiographic features of knee osteoarthritis and bone and cartilage markers

et al. 2011

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ADAM12 (A disintegrin and metalloprotease) is one of the candidate genes demonstrating susceptibility to osteoarthritis. The purpose of this study was to investigate the relationship between ADAM12-S protein and radiographic knee osteoarthritis (KOA) and its correlation to several bone and cartilage biomarkers. The ADAM12-S protein was measured in 276 subjects (60% women, aged 32-60 years), including 181 individuals with and 95 without radiographic KOA features. The radiographs were obtained from both tibiofemoral (TF) and patellofemoral (PF) joints. The serum levels of ADAM12-S protein were measured by DELFIA1/AutoDELFIA research kit. The ADAM12-S protein was found in detectable ranges in 43 subjects (16 men), without statistical difference between the two genders. In the whole group, the ADAM12-S was related to radiographic KOA grades in TF (P = 0.004) as well in PF joint (P = 0.003). We also found a correlation between ADAM12-S protein and osteophytes in TF and/or PF joints (P = 0.003). No correlations were found between serum levels of S-CTx-I (C-terminal cross-linked telopeptides of type I collagen) or S-PINP (type I procollagen N-terminal propeptide) and ADAM12-S. Similarly, in the whole group, the ADAM12-S protein was not correlated with U-CTx-II (urinary C-telopeptide fragments of type II collagen); however, in the female group, trend to positive correlation between the investigated biomarkers (P = 0.019) was observed. The ADAM12-S protein could be elevated in some KOA cases, and this elevation correlates with the grades of the disease, mostly owning to development of osteophytes. This finding suggests the possible involvement of the ADAM12-S protein in the pathogenesis of KOA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of ADAM12-S protein with radiographic features of knee osteoarthritis and bone and cartilage markers

et al. 2011

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“…Approval for the study was obtained from the Nottingham Research Ethics Committee. Study recruitment occurred from 2002 to 2006 (21).…”

Section: Methodsmentioning

confidence: 99%

“…To do this, we investigated the participants in the Genetics of Osteoarthritis and Lifestyle (GOAL) case-control study. This wellcharacterized group was primarily established for studying the genetic-environmental interaction in people with symptomatic, clinically severe knee and hip OA (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Self‐reported knee and foot alignments in early adult life and risk of osteoarthritis

McWilliams¹,

Doherty²,

Maciewicz³

et al. 2010

Arthritis Care & Research

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Objective. To determine whether self-reported early adult life malalignment of knees or feet are risk factors for knee or hip osteoarthritis (OA). Methods. Participants in the Genetics of Osteoarthritis and Lifestyle case-control database were sent a questionnaire (n ‫؍‬ 3,022) containing line-drawing instruments for self-reported knee and foot alignment at ages 20 -29 years. Respondents were categorized as having straight, valgus, or varus knee, and straight, toe-in, or toe-out feet. Radiographic criteria were used to define current isolated knee or hip OA, combined knee and hip OA, or non-OA controls. Odds ratios (ORs), adjusted ORs, and 95% confidence intervals (95% CIs) were calculated and logistic regression was performed. Results. The response rate was 72%; 87.5% of responders (n ‫؍‬ 1,901) completed the alignment questions. Increased risk of isolated knee OA occurred with early adult varus (adjusted OR 5.16, 95% CI 2.87-9.41) and valgus knees (adjusted OR 3.16, 95% CI 1.04 -9.64). The positive association between knee OA and toe-in foot was explained by varus knee. There was an increased risk of combined knee/hip OA from varus (adjusted OR 4.52, 95% CI 2.39 -8.53) and valgus knees (adjusted OR 3.07, 95% CI 0.99 -9.54). Varus knee was associated with risk of medial tibiofemoral OA, whereas valgus knee was associated with risk of lateral tibiofemoral and lateral patellofemoral OA. Toe-out foot was associated with reduced medial patellofemoral OA. For knee OA, a multiplicative interaction analysis between occupational risks and varus/valgus yielded an OR int of 3.20 (95% CI 1.08 -9.49). Conclusion. Constitutional alignment of the leg in terms of varus or valgus knee or foot rotation may be a significant factor in determining development and distribution of knee but not hip OA.

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“…GOAL study [27] utilized large number of symptomatic radiographic knee or hip OA and controls to replicate 68 variants in 12 genes including IL1A, IL1B, IL1RN, IL4R, IL6, COL2A1, ADAM12, ASPN, IGF1, TGFB1, ESR1 and VDR, but they did not replicate any of these associations. All the genetic variants they studied were included in our study.…”

Section: Discussionmentioning

confidence: 99%

Attempt to replicate the published osteoarthritis associated genetic variants in the Newfoundland & Labrador Population

Zhai¹,

Aref‐Eshghi²,

Rahman³

et al. 2014

J Orth Rheumatol

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Objective: Over 200 genes have been reported to be associated with osteoarthritis (OA), but most of them have not been replicated in an independent sample. Using the newly collected cohort from a genetically isolated population -the Newfoundland and Labrador population, we attempted to replicate 105 previously reported OAassociated SNPs. Methods:A case-control study design was utilized in this study. Patients undergoing total hip/knee joint replacements due to severe OA were collected as cases. A group of healthy individuals with no evidence of OA was used as controls.105 SNPs were genotyped either by Sequenom iPLEX Gold method or Illumina GWAS genotyping platform. The cross-reference was performed on both methods in a subset of samples for genotyping quality control. A logistic regression model was used to test for associations between the SNPs and OA.Results: A total of 126 cases and 348 healthy controls were included in the final analysis. OA Patients were on average 9 years older than healthy controls (p<0.0001), but there was no difference in BMI. We were unable to replicate the previously reported associations. Two SNPs, rs2294995 (COL9A3), and rs1049007 (BMP2) showed an association with p<0.05, but the significance did not survive the Bonferroni multiple testing correction. Conclusion:A lack of replication might be due to study design, complexity of OA, method of OA ascertainment, populations studied, or false positives in the original publications. A study with larger sample is needed to confirm the two possible SNPs with OA.

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Attempt to replicate published genetic associations in a large, well-defined osteoarthritis case–control population (the GOAL study)

Cited by 41 publications

References 31 publications

Association of ADAM12-S protein with radiographic features of knee osteoarthritis and bone and cartilage markers

Association of ADAM12-S protein with radiographic features of knee osteoarthritis and bone and cartilage markers

Self‐reported knee and foot alignments in early adult life and risk of osteoarthritis

Attempt to replicate the published osteoarthritis associated genetic variants in the Newfoundland & Labrador Population

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