Arthritis Research UK Osteoarthritis Genetics (arcOGEN) is a collection of 7410 unrelated, UK-based individuals of European ancestry with knee and/or hip osteoarthritis from the arcOGEN Consortium. Samples were collected in 2 stages from 10 United Kingdom locations (London, Nottingham, Oxford, Sheffield, Southampton, Edinburgh, Newcastle-Upon-Tyne, Sheffield, Wansbeck, and Worcester). The majority of cases had primary OA requiring joint replacement of the hip or knee while a smaller number were ascertained by radiographic evidence of disease (Kellgren-Lawrence (KL) grade ≥2). The exclusion criteria included the need for joint replacement due to fracture, secondary OA of any cause, and developmental, vascular, or infective causes of joint disease.
Arthroplasty and the Genetics of Osteoarthritis- The ARGO study
The ARGO study, was set up to investigate the genetic architecture of hip and knee OA in a Greek population.
More than 1,500 patients with severe OA, undergoing hip and/or knee total joint replacement were recruited from the cities of Athens and Larissa.
The ARGO-Larissa study was set up to investigate the genetic architecture of knee OA in a Greek population.
It included individuals with primary knee OA undergoing total knee arthroplasty.
The osteoarthritis participants’ recruitment was conducted in the city of Larissa, central Greece.
China Kadoorie Biobank
The China Kadoorie Biobank (CKB) is a prospective cohort of 512,000 adults aged 30-79 years, recruited from ten rural and urban areas of China during 2004-2008. At baseline, socio-demographic, lifestyle and medical history data were collected by questionnaire, physical measurements were undertaken and a blood sample was collected. Long-term follow-up is through linkage to death and disease registries and health insurance records recording all hospitalised events. Genome-wide genotyping data from a custom-designed array are available for 100,000 participants. Clinical biochemistry, metabolomic and proteomic data are available in smaller subsets of participants.
Cohort hip & cohort knee
CHECK (Cohort hip & cohort knee) is a multi centre cohort sponsored by the Dutch Arthritis Foundation (DAF) with over 1000 participants with pain of hip and/or knee expected to develop knee and or hip OA. The objective of CHECK is to study the course of complaints, the mechanisms that cause joint damage, and to identify markers for diagnosis and prognosis, as well as to identify prognostic factors that predict and explain the course of OA.
The deCODE genetics osteoarthritis study
The deCODE genetics osteoarthritis study is an ongoing population based study in Iceland that was initiated in 1997. The study includes information on all subjects who have undergone total joint replacement in Iceland, and on osteoarthritis status from the Landspitali University Hospital electronic health records. Information on hand osteoarthritis patients is derived from a database of hand osteoarthritis patients that was initiated in 1972.
Subjects have given blood or buccal samples to deCODE genetics biobank, which has gathered genotypic and medical data from more than 160,000 volunteer participants.
Estonian Genome Center of the University of Tartu
EGCUT has 52000 gene donors, who are all genotyped. In 2019, 100000 new donors will be collected and genotyped. All osteoarthritis cases were selected from Estonian Biobank which is a population-based biobank of the EGCUT.
The FinnGen study, launched in Finland in the autumn of 2017, is a study that combines genome information with digital health care data from national registries. The aim is to get 500,000 Finns to participate in the study through donations of samples to biobanks. The project aims to improve human health through genetic research, and ultimately identify new therapeutic targets and diagnostics for treating numerous diseases. FinnGen brings together Finnish universities, the nation-wide network of Finnish biobanks, hospitals and hospital districts, the National Institute for Health and Welfare, Business Finland and nine international pharmaceutical companies: Abbvie, AstraZeneca, Biogen, Celgene, Genentech (a member of the Roche Group), GSK, Merck & Co., Pfizer and Sanofi. The current FinnGen data freeze 3 (spring 2019), consists of 135,638 individuals for whom genetic analyses have been conducted. For osteoarthritis (OA), the information on all subjects who have osteoarthritis status in the Finnish National Electronic Health Registers with or without total joint replacement is available. GWAS data is available for OA at any site, hip OA, knee OA and hip-knee OA as well as severe knee or hip OA with total knee or hip joint replacement.
The Generation Scotland (GS) Scottish Family Health Study is an intensively phenotyped, family-based cohort for the study of the genetic basis of common complex diseases and response to treatments. Recruitment began early in 2006 and was completed in 2011, funded by the Scottish Government Chief Scientist Office. The cohort includes just over 24,000 participants from 7,000 families, with most consenting to health record linkage and recontact.
Each participant gave blood or saliva samples (for processing, biochemistry and cryopreservation) and a urine sample. The blood or saliva samples were processed to DNA and extensive genotyping was carried out on over 20,000 participants by 2015, funded by the MRC and Wellcome Trust. In 2019 epigenetic (DNA methylation) analysis was completed on 10,000 participants.
Genetics, Arthrosis and Progression study
The GARP study is a prospective observational study in patients with familial generalized osteoarthritis, hand osteoarthritis and other osteoarthritis phenotypes. All patients have symptoms and definite radiological signs of osteoarthritis and represent an advanced disease state.
Geisinger is an integrated health care provider located in central and northeastern Pennsylvania and New Jersey. Geisinger’s electronic health record (EHR) consists of comprehensive longitudinal clinical information including patients’ demographic data, diagnoses (including co-morbidities), lab measurements, prescriptions, procedures, vital signs, and, of relevance for this study, surgical procedure logs. The EHR captures a median of 14 years of health data for patients within the MyCode® Community Health Initiative biorepository. Through the Geisinger-Regeneron DiscovEHR collaboration, whole exome sequence and genome wide genotype data are available from more than 92,000 MyCode® participants to date. These high dimensional clinical data linked to genetic data provide opportunities to conduct precision health research at an unprecedented scale that can lead to significant clinical insights.
Hong Kong Degenerative Disc Disease Cohort
HKDDDC is a community-based study. Volunteers of southern Chinese ancestry living in Hong Kong were recruited for assessment which included a questionnaire for low back pain and associated symptoms and sagittal T2-weighted fast spin-echo MRI of the spine. A proportion of subjects also underwent posteroanterior and lateral whole spine radiographs. Diagnoses of spine osteoarthritis (OA) were made from MRI data, using criteria established by comparison with X-ray data. The aim of HKSPINEOA study is to identify common genetic variants that are associated with spine osteoarthritis, in order to gain insights on the biological mechanisms of the disorder.
Other objectives of HKDDDC study include:
• To clarify the relationships between multiple MRI and X-ray features at all lumbar disc levels
• To identify common genetic and environmental risk factors of MRI and X-ray features of spine OA
• To classify the MRI and X-ray features of spine OA based on their relationships with risk factors
The HUNT Study is a longitudinal, population-based health study, which has been conducted in the county of Nord-Trøndelag, Norway, since 1984. The county’s population has been invited to contribute with questionnaire-based health data as well as clinical examinations and participation in numerous sub-studies. The HUNT surveys have so far included a total of 130 000 participants, and HUNT 4, currently ongoing, have an expected inclusion of 50 000 participants.
The HUNT Biobank (ISO-9001) has been holding biological samples since 1995, and is now a modern state-of-the-art facility. It was awarded the "European Research Biobank of the Year 2013". We have established the largest genetic database in Norway and our main data resource consists of genome-wide genotype data from ~70,000 individuals from the HUNT study, linked to a wide range of national population registries, electronic health records and surveys.
Japanese OA cohort
The Japanese cohort of knee OA GWAS (disease cohort) consists of 900 cases and 3,400 controls. The cases were all symptomatic OA. They were diagnosed and recruited by expert orthopedic surgeons based on clinical and radiographic examination. All had clinical records for OA and radiographs (standing knee A-P). The controls were obtained from Biobank Japan. The genotyping was done by using Illumina HumanHap550v3 Genotyping BeadChip. After excluding cases with call rate of <0.98, we applied SNP QC (call rate of ≥0.99 in both cases and controls and P value of Hardy-Weinberg equilibrium test of ≥1.0×10−6 in controls). Finally, 459,393 SNPs on autosomal chromosomes passed the QC filters (Nakajima M, et al. PLoS One 18;5(3):e9723, 2010.
Leiden Longevity Study
The Leiden Longevity Study consists of 420 Caucasian families with at least two long-lived siblings (men aged 89 years or above; women aged 91 years or above), the middle aged offspring and the partners of this offspring. The aim of this research is to identify genomic and biochemical parameters associated with human longevity by combining research in familial long-lived individuals and their family members and in sporadic long-lived individuals from the general population.
The Norwegian Arthroplasty Register
In 1985, the Norwegian Orthopaedic Association decided to establish a national hip register, and the Norwegian Arthroplasty Register was started in 1987. In January 1994, it was extended to include all artificial joints. The main purpose of the register is to detect inferior results of implants as early as possible. All hospitals participate, and the orthopedic surgeons are supposed to report all primary operations and all revisions. The register contains information on 221,913 hip arthroplasties, 89,410 knee arthroplasties, 8,466 shoulder arthroplasties and 9,949 arthroplasties in other joints. In 2017 10,583 hip arthroplasties and 7,188 knee arthroplasties were operated and we received reports from 57 Norwegian hospitals.
Nurses' Health Studies
The Nurses' Health Studies are among the largest prospective investigations into the risk factors for major chronic diseases in women.
Self-reported cases of total hip replacement were analyzed for GO meta-analysis.
PISA & QIMR Studies
Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA Study)
The scientific aims of the PISA Study are to predict healthy and pathological ageing, quantify behavioural and psychological phenotypes, establish a cohort of patients with pre-clinical AD for future testing of interventions, and to inform novel diagnostic criteria for subtypes of disease (including stages before clinical symptoms occur). All participants in previous studies conducted by the Genetic Epidemiology group at QIMR Berghofer Medical Research Institute who were aged 40-70 years old and had genome-wide genotype data available (N=~15000) were invited to participate in the PISA Study. Self-report osteoarthritis data collected between 2018 and 2019 in the ‘Pain and Health’ section of the online questionnaire is available for 1,539 PISA participants (note: PISA data collection is ongoing). OA data is available for OA at any site, hip OA, knee OA, hip-knee OA, hand OA, spine OA, total joint replacement, total knee replacement and total hip replacement.
Over 50’s (Aged) and Osteoarthritis (OA) Studies
The QIMR cohort consists of twins recruited to two studies conducted at QIMR Berghofer Medical Research Institute: the Over 50’s (Aged) and Osteoarthritis (OA) Studies.
The Aged Study was conducted in 1993 as a multi-wave mailout to 4562 twins (2281 pairs) aged over 50 years old who were registered with the Australian Twin Registry. In total, 3116 individuals (1279 complete pairs and 558 singles) completed and returned the 16-page questionnaire form. Self-report osteoarthritis data was collected in the ‘Bones and Joints’ section in collaboration with the Australian Arthritis Foundation, and in consultation with Nick Bellamy and David Duffy. Participants were questioned about ever having experienced pain, swelling or stiffness in any joints; prior diagnosis of osteoarthritis or degenerative arthritis, rheumatoid arthritis, and other forms of arthritis or rheumatism; as well as prior bone fracture or joint injury. Self-report of pain and/or swelling in the joints of the hands, hips and knees were used as indicators of potential osteoarthritis, excluding those joints indicated to have sustained prior injury. Genome-wide data are available for 933 participants for OA at any site and age of onset for OA.
The OA Study was designed to investigate how similar identical and non-identical twins are to each other and reach an estimate of the effect of genetic and environmental influences on OA in the general population. The study conducted in 1994 where 441 twin pairs answered questions about prior diagnosis of OA; presence of pain or swelling in target joints for OA; and onset of joint pain/swelling not due to trauma after age 45. In addition, clinical examinations were performed by three Rheumatologists on 159 subjects, where approximately half were considered to be normal. Examinations of the twin's medical records and joint radiographs were conducted, where available. OA diagnosis involved comparing the self-report, clinical examination and radiological assessments. GWAS data is available for 1,073 participants (including 931 of the Aged Study participants) for OA at any site, hip OA, knee OA, hand OA and hip-knee OA.
Research Arthritis and Articular Cartilage study
The RAAK study is aimed at the biobanking of joint materials as well as mesenchymal stem cells and primary chondrocytes from patients (paired preserved and OA affected cartilage samples) and controls in the Leiden University Medical Center and collaborating outpatient clinics in the Leiden area in The Netherlands.
The Rotterdam study is a large longitudinal population-based cohort study designed to study the risk factors for all major diseases of the elderly. The study started in 1991, has grown to up to 15000 individuals and has detailed phenotyping for cardiovascular, neurodegenerative, endocrine and locomoter diseases and more. For osteoarthritis, longitudinal X-rays on multiple joints and knee MRI’s are available (and scored), as well as information on joint pain. GWAS data is available for all individuals of the Rotterdam Study, as well as additional molecular layers (such as RNA, methylation, microbiome). Genomic studies in the Rotterdam Study are led by the Genetic Laboratory, Department of Internal Medicine of the ErasmusMC in Rotterdam.
United Kingdom Household Longitudinal Study (UKHLS) also known as Understanding Society, is a longitudinal panel survey of 40,000 UK households (England, Scotland, Wales and Northern Ireland) representative of the UK population. Participants are surveyed annually since 2009 and contribute information relating to their socioeconomic circumstances, attitudes, and behaviours via a computer assisted interview. The study includes phenotypical data for a representative sample of participants for a wide range of social and economic indicators as well as a biological sample collection encompassing biometric, physiological, biochemical, and haematological measurements and self-reported medical history and medication use.