Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

Purpose: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA.

Methods: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA.

Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization.

Objective: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors.

Methods: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors.

Do associations with hand OA vary by knee osteoarthritis phenotype? Cross-sectional data from the Multicenter Osteoarthritis Study.

Objective: Osteoarthritis (OA) is highly heterogeneous and has both biomechanical and systemic components that may not have the same etiology. We therefore aimed to identify specific knee OA phenotypes that may be more strongly associated with hand OA to refine the criteria used to define multi-joint OA.

Design: We assessed data from the Multicenter Osteoarthritis Study (MOST).

Validation of knee osteoarthritis case identification algorithms in a large electronic health record database.

Purpose: To facilitate studies of knee osteoarthritis (OA) in large databases, case finding algorithms with high levels of diagnostic performance are needed.

Methods: From a UK general practitioner (GP) practice derived database, we selected adults ages 40-90 years meeting algorithms that included various combinations of codes for knee OA or knee pain and imaging. The GP for each patient was mailed a questionnaire to assess the cause of knee pain and provide knee x-ray and/or MRI findings.

A Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations.

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD.

Association between disease progression and depression onset in persons with radiographic knee osteoarthritis.

Objectives: Osteoarthritis (OA) disease progression may lead to deteriorating psychosocial function, but it is unclear what aspects of disease severity are related to the onset of depression. This study assessed which components of OA disease progression cumulatively contribute to depression onset in persons with radiographic knee OA.

Methods: Osteoarthritis Initiative participants (n = 1651) with radiographic disease (Kellgren-Lawrence grade ≥2) in one or both knees and below the screening threshold for probable depression [Center for Epidemiological Studies Depression (CES-D) scale <16] at baseline were included.

Author Correction: Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

Background: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus.

Interleukin 1 receptor antagonist () gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease.

Objective: In these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA).

Methods: Over 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health (NIH)-funded cohorts.

Depression Subtypes in Individuals With or at Risk for Symptomatic Knee Osteoarthritis.

Objective: The present study was undertaken to identify depression subtypes in individuals with or at risk for symptomatic knee osteoarthritis (OA) and to evaluate differences in pain and disability trajectories between groups.

Methods: Participants (n = 4,486) were enrolled in the Osteoarthritis Initiative. Latent class analysis was applied to the 20-item Center for Epidemiologic Studies Depression Scale measured at baseline to identify groups with similar patterns of depressive symptoms, and subtypes were assigned using posterior probability estimates.

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain.

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release.

Dynamic Effects of Depressive Symptoms on Osteoarthritis Knee Pain.

Objective: To estimate the dynamic causal effects of depressive symptoms on osteoarthritis (OA) knee pain.

Methods: Marginal structural models were used to examine dynamic associations between depressive symptoms and pain over 48 months among older adults (n = 2,287) with radiographic knee OA (Kellgren/Lawrence grade 2 or 3) in the Osteoarthritis Initiative. Depressive symptoms at each annual visit were assessed (threshold ≥16) using the Center for Epidemiologic Studies Depression Scale.

Depressive symptoms and structural disease progression in knee osteoarthritis: data from the Osteoarthritis Initiative.

Depressive symptoms are associated with increases in pain and functional limitations in knee osteoarthritis (OA). The aim was to determine whether depressive symptoms are also associated with greater structural knee OA progression. Four years of annual radiographic and clinical assessments from the Osteoarthritis Initiative were analyzed.

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health.

Heritability of Thoracic Spine Curvature and Genetic Correlations With Other Spine Traits: The Framingham Study.

Hyperkyphosis is a common spinal disorder in older adults, characterized by excessive forward curvature of the thoracic spine and adverse health outcomes. The etiology of hyperkyphosis has not been firmly established, but may be related to changes that occur with aging in the vertebrae, discs, joints, and muscles, which function as a unit to support the spine. Determining the contribution of genetics to thoracic spine curvature and the degree of genetic sharing among co-occurring measures of spine health may provide insight into the etiology of hyperkyphosis.

Pantomime-grasping: the 'return' of haptic feedback supports the absolute specification of object size.

When an individual grasps a physical object, the visuomotor system is able to specify grip aperture via absolute visual information. In contrast, grasping to a location previously occupied by an object (i.e.

Association analysis of BMD-associated SNPs with knee osteoarthritis.

Osteoarthritis (OA) risk is widely recognized to be heritable but few loci have been identified. Observational studies have identified higher systemic bone mineral density (BMD) to be associated with an increased risk of radiographic knee osteoarthritis. With this in mind, we sought to evaluate whether well-established genetic loci for variance in BMD are associated with risk for radiographic OA in the Osteoarthritis Initiative (OAI) and the Johnston County Osteoarthritis (JoCo) Project.

Genetic epidemiology of osteoarthritis: recent developments and future directions.

Purpose Of Review: Despite the high prevalence of osteoarthritis and its enormous public health impact, the cause of the disease remains largely obscure. The identification of genes associated with osteoarthritis can help reveal underlying biological mechanisms that may lead to development of new therapeutic targets or biomarkers for early detection and risk stratification. The goal of this short review is to provide a brief overview of the current status of genetics of osteoarthritis with an emphasis on developments generated in the last year.