Review
Orthopedics
M. Kim, A. Rubab, W. C. W. Chan, D. Chan
Summary: This review summarizes the research findings on genetics, genomics, and epigenetics for osteoarthritis (OA) between Mar 2021-Apr 2022. A total of 695 unique research articles and 112 reviews were identified and 90 selected as references. The trend in genetics is focused on meta-analysis and defining sub phenotypes, while epigenetics is gaining attention with studies on miRNA and long non-coding RNA. The review provides new insights and a roadmap for future research in OA prevention and treatment.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Review
Orthopedics
D. A. Young, M. J. Barter, J. Soul
Summary: This review highlights the advances in genetics, genomics, and epigenetics in the field of osteoarthritis over the past year, focusing on the application of new technologies and the investigation of interactions between multiple tissue types to enhance our understanding of disease mechanisms.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Editorial Material
Multidisciplinary Sciences
Ran Elkon, Reuven Agami
Summary: Basic design principles that protect enhancer networks against the harmful effects of genetic mutations have been elucidated.
Review
Cell Biology
Emmanuelle A. Vire, Simon Mead
Summary: Epigenetics plays a key role in normal development and disease, and has been proposed as biomarkers for many diseases. Prion diseases are closely associated with human aging, cell type and differentiation, and human risk factors, suggesting the involvement of epigenetic mechanisms.
CELL AND TISSUE RESEARCH
(2023)
Article
Immunology
Catherine M. Stein, Penelope Benchek, Jacquelaine Bartlett, Robert P. Igo, Rafal S. Sobota, Keith Chervenak, Harriet Mayanja-Kizza, C. Fordham von Reyn, Timothy Lahey, William S. Bush, W. Henry Boom, William K. Scott, Carmen Marsit, Giorgio Sirugo, Scott M. Williams
Summary: This study identified specific epigenetic changes in HIV-infected individuals exposed to TB but remaining disease free, which could potentially enhance resistance to tuberculosis in conjunction with genetic variants.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Endocrinology & Metabolism
Khanh Trang, Struan F. A. Grant
Summary: Obesity is a complex trait influenced by both genetic and environmental factors. Advances in genomic technologies have led to the identification of genetic loci associated with obesity, while epigenetic modifications to the genome have been found to play a role as well. This review provides an overview of the genetic and epigenetic contributors to obesity susceptibility and discusses potential mechanisms of action for future interventions.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Article
Oncology
Elizabeth Pan, Angelo Cabal, Juan Javier-DesLoges, Devin Patel, Justine Panian, Suzanna Lee, Justin Shaya, Taylor Nonato, Xiaojun Xu, Tyler Stewart, Brent Rose, Ahmed Shabaik, Ezra Cohen, Razelle Kurzrock, Pablo Tamayo, Rana R. McKay
Summary: CDK12 alterations are rare events across hematologic and solid tumor malignancies. They represent a clinically distinct molecular cancer subtype which may have increased responsiveness to checkpoint inhibition. Prospective studies are warranted to investigate checkpoint inhibition in CDK12-altered tumors.
Review
Radiology, Nuclear Medicine & Medical Imaging
Vratko Himic, Nikolaos Syrmos, Gianfranco K. I. Ligarotti, So Kato, Michael G. Fehlings, Mario Gonau
Summary: Osteoporosis predisposes patients to spinal fragility fractures, and imaging plays a key role in their diagnosis and prognostication. However, the current imaging knowledge for osteoporotic vertebral fractures (OVF) lacks standardisation, hindering effective risk prognostication. Differences in OVF prevalence between Caucasian and Eastern Asian populations suggest potential genetic and epigenetic factors driving osteoporosis, low bone mineral density (BMD), and OVF development. Certain genetic loci have been associated with a higher risk of vertebral fractures, although the specificity to OVF or osteoporosis in general remains unclear. Biomarkers, including novel non-coding RNAs, miRNAs, and circRNAs, could be utilized for diagnostic interpretation. Additionally, gene methylation and histone modifications affect pathways regulating bone deposition and resorption, impacting osteoblast and osteoclast differentiation. Furthermore, new imaging modalities show promise for assessing bone quality alongside BMD and bone structure, with advancements spanning from pre-clinical to clinical stages. This mini review explores the genetic and epigenetic factors associated with spinal fragility fractures and outlines the potential diagnostic impact of cutting-edge imaging methods for OVF.
QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
(2023)
Review
Endocrinology & Metabolism
Matthew Dapas, Andrea Dunaif
Summary: Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age, characterized by reproductive abnormalities, insulin resistance, and obesity. Genetic and environmental factors contribute to the development of PCOS. Genomic studies have provided insights into disease pathways and highlighted the limitations of current diagnostic criteria. Future research will focus on understanding the genetic mechanisms of PCOS.
Editorial Material
Multidisciplinary Sciences
Ludovic Orlando
Summary: An extensive genomic time series has been conducted on 356 humans from ice-age Europe, showing the impact of climate change on the migration patterns and cultural development of hunter-gatherer populations.
Editorial Material
Multidisciplinary Sciences
Karen H. Miga
Summary: Since the publication of the human genome in 2001, advancements in sequencing technology have filled in many of the gaps in the original sequence, leading to a deeper knowledge of genome regulation, structure, and function.
Editorial Material
Multidisciplinary Sciences
Conrad O. Iyegbe, Paul F. O'Reilly
Summary: Rare and common genetic variants associated with schizophrenia provide convergent clues about the underlying biology of this complex disorder.
Editorial Material
Multidisciplinary Sciences
Charles N. Rotimi, Adebowale A. Adeyemo
Summary: Over the past 20 years, the increasing diversity in genomic sequencing has provided valuable insights into our evolutionary history and health status.
Editorial Material
Multidisciplinary Sciences
Maggie P. Lauria Sneideman, Victoria H. Meller
Summary: A protein that upregulates gene expression of the X chromosome has been discovered in male mosquitoes, which is crucial for equalizing gene expression between sexes in organisms with X and Y chromosomes.
Review
Biochemistry & Molecular Biology
Erik A. Ovrom, Karson A. Mostert, Shivani Khakhkhar, Daniel P. McKee, Padao Yang, Yeng F. Her
Summary: This narrative review provides an overview of the current understanding of the genetic and epigenetic contributions to the development of fibromyalgia (FM). While no single gene has been identified as the cause of FM, this study suggests that certain genetic polymorphisms involved in various pathways may influence susceptibility to FM and the severity of its symptoms. Additionally, epigenetic changes at the DNA level and the impact of microRNAs on protein expression are also implicated in the development and worsening of FM-associated symptoms.
Review
Orthopedics
G. Aubourg, S. J. Rice, P. Bruce-Wootton, J. Loughlin
Summary: Osteoarthritis genetics has made significant progress through large-scale genome-wide association scans. Over 100 genetic risk variants associated with osteoarthritis have been identified, accounting for more than 20% of its heritability. These variants are mainly located in non-protein coding regions of the genome and regulate the expression of target genes. Epigenetic factors, particularly cartilage DNA methylation changes, are also correlated with some of these variants, suggesting a potential mediation of genetic effects on gene expression.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Article
Rheumatology
Alejandro Rodriguez Ruiz, Margo Tuerlings, Ankita Das, Rodrigo Coutinho de Almeida, H. Eka D. Suchiman, Rob G. H. H. Nelissen, Yolande F. M. Ramos, Ingrid Meulenbelt
Summary: This study determined the role of TNFRSF11B overexpression in the development of OA and found that it may act as a direct driving factor for the transition of chondrocytes to osteoblasts in lesioned OA cartilage, independent of the OPG/RANK/RANKL pathway commonly seen in bone remodeling.
Review
Biochemistry & Molecular Biology
John Loughlin
Summary: The ultimate goal of molecular genetic studies of human diseases is to benefit patients through translation of discoveries. The lack of licensed disease-modifying therapies for diseases like osteoarthritis (OA) creates an urgent need. OA is a polygenic disease that primarily affects older individuals, and recent genome-wide studies have identified 52 novel association signals. Many of these signals involve effector genes that encode proteins targeted by drugs for other indications, indicating potential repurposing opportunities. This article discusses the potential for translating OA genetic data and whether the developmental origin of OA may limit its use for disease modification.
TRENDS IN MOLECULAR MEDICINE
(2022)
Article
Orthopedics
S. Monteagudo, F. M. F. Cornelis, X. Wang, A. de Roover, T. Peeters, J. Quintiens, A. Sermon, R. C. de Almeida, I Meulenbelt, R. J. Lories
Summary: ANP32A is identified as a novel repressor of Wnt signaling in articular cartilage, and its loss leads to hyper-activation of Wnt signaling. ANP32A inhibits target gene expression by histone acetylation masking. The study also reveals the involvement of ANP32A in cardiac hypertrophy. These findings have significant implications for understanding the pathogenesis of osteoarthritis and cardiac diseases.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Article
Rheumatology
Eefje M. van Helvoort, Mylene P. Jansen, Anne C. A. Marijnissen, Margreet Kloppenburg, Francisco J. Blanco, Ida K. Haugen, Francis Berenbaum, Anne-Christine C. Bay-Jensen, Christoph Ladel, Agnes Lalande, Jonathan Larkin, John Loughlin, Ali Mobasheri, Harrie H. Weinans, Pawel Widera, Jaume Bacardit, Paco M. J. Welsing, Floris P. J. G. Lafeber
Summary: The IMI-APPROACH knee osteoarthritis study used machine learning to predict structural and pain progression. The study found that the predicted-progression scores were able to somewhat distinguish between actual progressors and non-progressors, with better prediction for pain progression than for structural progression.
Editorial Material
Rheumatology
Michelle S. Yau, John Loughlin
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Rheumatology
Zoe Paskins, Clare E. Farmer, Fay Manning, David A. Andersson, Tim Barlow, Felicity L. Bishop, Christopher A. Brown, Amanda Clark, Emma M. Clark, Debra Dulake, Malvika Gulati, Christine L. Le Maitre, Richard K. Jones, John Loughlin, Deborah J. Mason, Maura McCarron, Neil L. Millar, Hemant Pandit, George Peat, Stephen M. Richardson, Emma J. Salt, E. Jane Taylor, Linda Troeberg, Ruth K. Wilcox, Elspeth Wise, Colin Wilkinson, Fiona E. Watt
Summary: Involving research users in setting research priorities is crucial for patient-centered outcomes and maximizing value and impact. This study used the Child Health and Nutrition Research Initiative (CHNRI) method to identify key research priorities for musculoskeletal disorders. The priorities included developing new treatments, improving treatment targeting, early diagnosis, prevention, and understanding and management of pain.
LANCET RHEUMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah J. Rice, Abby Brumwell, Julia Falk, Yulia S. Kehayova, John Casement, Eleanor Parker, Ines M. J. Hofer, Colin Shepherd, John Loughlin
Summary: This study investigates the activity and impact of genetic risk factors for osteoarthritis (OA) during human skeletogenesis. It shows that OA genetic risk is present during fetal development and is associated with allelic expression imbalances of specific genes. These findings are significant for understanding the pathogenesis of OA and developing pharmacological interventions.
HUMAN MOLECULAR GENETICS
(2023)
Article
Rheumatology
Rodrigo Coutinho de Almeida, Margo Tuerlings, Yolande Ramos, Wouter Den Hollander, Eka Suchiman, Nico Lakenberg, Rob G. H. H. Nelissen, Hailiang Mei, Ingrid Meulenbelt
Summary: This study presents an unbiased approach to identify positional transcript SNPs associated with osteoarthritis (OA) risk loci using allelic expression imbalance (AEI) analyses. By prioritizing proxy transcript SNPs that mark AEI in cartilage and/or subchondral bone at loci harbouring GWAS signals, the study identifies 10 new potential OA risk genes ready for further exploration of their underlying biological mechanisms.
Article
Rheumatology
Yulia S. Kehayova, J. Mark Wilkinson, Sarah J. Rice, John Loughlin
Summary: This study aims to determine the target gene(s) and mechanism of action of the osteoarthritis (OA) locus. It was found that COLGALT2 is the target gene of this OA locus, and its expression is regulated by DNA methylation.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
Reem Assi, Chahrazad Cherifi, Frederique M. F. Cornelis, Qiongfei Zhou, Lies Storms, Sofia Pazmino, Rodrigo Coutinho de Almeida, Ingrid Meulenbelt, Rik J. J. Lories, Silvia Monteagudo
Summary: The methylation of H3K79me is reduced in osteoarthritis. Histone demethylase families, such as Jumonji-C and KDM2/7, can increase the levels of H3K79me and targeting KDM2/7 can protect joints against osteoarthritis.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Orthopedics
Ritchie G. M. Timmermans, Arjen B. Blom, Rob G. H. H. Nelissen, Demien Broekhuis, Peter M. van der Kraan, Ingrid Meulenbelt, Martijn H. J. van den Bosch, Yolande F. M. Ramos
Summary: The dysregulation of Wnt signaling plays a key role in the development and progression of osteoarthritis (OA). This study investigates how mechanical stress (MS) and inflammation independently affect Wnt signaling in human neocartilage and its relationship to OA pathophysiology. Results show that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Article
Rheumatology
Yulia S. Kehayova, J. Mark Wilkinson, Sarah J. Rice, John Loughlin
Summary: Investigation reveals that DNA variants rs11583641 and rs1046934 decrease methylation status and increase expression of COLGALT2 in cartilage, marking risk for osteoarthritis. This study investigates if these effects are present in non-cartilaginous joint tissues.
ARTHRITIS RESEARCH & THERAPY
(2023)
Article
Geriatrics & Gerontology
Ilja Boone, Margo Tuerlings, Rodrigo Coutinho de Almeida, Johannes Lehmann, Yolande Ramos, Rob Nelissen, Eline Slagboom, Peter de Keizer, Ingrid Meulenbelt
Summary: This study characterized the heterogeneity of cellular senescence within aged articular cartilage and explored the presence of corresponding metabolic profiles in blood as representative biomarkers. Two robust cellular senescent endotypes were identified, with one enriched for cell proliferating pathways and the other enriched for inflammation-associated pathways. Corresponding metabolic clusters were found in the blood samples. These non-invasive metabolic profiles could serve as biomarkers for targeted senescence treatment in osteoarthritis patients.
Article
Rheumatology
Abby Brumwell, Guillaume Aubourg, Juhel Hussain, Eleanor Parker, David J. Deehan, Sarah J. Rice, John Loughlin
Summary: This study investigated a genetic locus associated with osteoarthritis and identified TMEM129 as a target gene at the locus. The genotype at rs11732213 was found to impact the DNA methylation at an enhancer, which in turn modulated TMEM129 expression. This research provides new insights into the susceptibility of osteoarthritis.
ARTHRITIS RESEARCH & THERAPY
(2022)
