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TwinsUK is a nation-wide registry of volunteer twins in the United Kingdom, with about 12,000 registered twins (83% female, equal number of monozygotic and dizygotic twins, predominantly middle-aged and older). Over the last 20 years, questionnaire and blood/urine/tissue samples have been collected on over 7,000 subjects, as well as three comprehensive phenotyping assessments in the clinical facilities of the Department of Twin Research and Genetic Epidemiology, King's College London. The primary focus of study has been the genetic basis of healthy aging process and complex diseases, including cardiovascular, metabolic, musculoskeletal, and ophthalmologic disorders. Alongside the detailed clinical, biochemical, behavioral, and socio-economic characterization of the study population, the major strength of TwinsUK is availability of several ‘omics’ technologies for the participants. These include genome-wide scans of single nucleotide variants, next-generation sequencing, exome sequencing, epigenetic markers (MeDIP sequencing), gene expression arrays and RNA sequencing, telomere length measures, metabolomic profiles, and gut flora microbiomics. The scientific community now can freely access parts of the phenotype data from the ‘TwinsUK’, and interested researchers are encouraged to contact us via our Web site (www.twinsuk.ac.uk) for future collaborations. [ABSTRACT FROM AUTHOR]

The UK's largest registry of adult twins, or TwinsUK Registry, started in 1992 and encompasses about 12 000 volunteer twins from all over the United Kingdom. More than 70% of the registered twins have filled at least one detailed health questionnaire and about half of them undergone a baseline comprehensive assessment and two follow-up clinical evaluations. The most recent follow-up visit, known as Healthy Ageing Twin Study (HATS), involved 3125 female twins aged >40 years with at least one previous clinical assessment to enable inspection of longitudinal changes in ageing traits and their genetic and environmental components. The study benefits from several state-of-the-art OMICs studies including genome-wide association, next-generation genome and transcriptome sequencing, and epigenetic and metabolomic profiles. This makes our cohort as one of the most deeply phenotyped and genotyped in the world. Several collaborative projects in the field of epidemiology of complex disorders are ongoing in our cohort and interested researchers are encouraged to get in contact for future collaborations. [ABSTRACT FROM PUBLISHER]

Summary: We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. Purpose: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. Methods: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. Results: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52–73% at 6 months to 29–53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50–66% at 6 months and decreased to 30–44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40–73% and decreased to 25–59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50–85% (6 month), 30–63% (12 month) and with teriparatide 40–75% (6 month) decreasing to 21–54% (12 month). Switching occurred most frequently in the alendronate group (2.8–5.8%) and in the teriparatide group (7.1–14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. Conclusion: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare. [ABSTRACT FROM AUTHOR]

The association of FTO gene variants with body mass index (BMI) and other obesity characteristics is well established. However, uncertainties remain whether the association is present only in young populations and whether it is attributable to body fat mass specifically. We aimed to clarify these two questions in a large sample ( N= 4,523 individuals) of middle-aged and older (range 40-80 years) British female twins. The women were assessed for BMI, waist and hip circumference, total lean (LBM) and fat (FBM) body mass. Since the majority of FTO association signals have been reported in a haploblock bordering 52,355-52,408 kb (on chromosome 16q12.2), we examined five genotyped and 43 imputed SNPs mapped to this block. Canonical correlation and other association analyses showed significant and consistent association between the selected SNP and studied body composition phenotypes, with p-values reaching p= 0.000004. Of particular interest, in addition to the expected significant associations between FTO variants and FBM, we also identified significant associations with LBM. These results suggest that the association between FTO variants and body composition phenotypes is present across a wide range of ages, and that FTO appears primarily to affect the amount of body soft tissue, influencing both fat and lean mass. [ABSTRACT FROM AUTHOR]

Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n = 2444) from the TwinsUK registry who had extensive clinical, anthropometric, and "omic" data were included. Nontargeted metabolomics screening including 324 metabolites was carried out for CWP and body composition using dual-energy X-ray absorptiometry. The biological basis of these associations was explored through a genome-wide association study and replicated in an independent population sample (Cooperative Health Research in the Region of Augsburg [KORA] study, n = 2483). A causal role for the genetic variants identified was sought in CWP using a Mendelian randomisation study design. Fat mass/height2 was the body composition variable most strongly associated with CWP (TwinsUK: P = 2.4 × 10(-15) and KORA: P = 1.59 × 10(-10)). Of 324 metabolites examined, epiandrosterone sulfate (EAS) was highly associated with both CWP (P = 1.05 × 10(-09) in TwinsUK and P = 3.70 × 10(-06) in KORA) and fat mass/height2. Genome-wide association study of EAS identified imputed single nucleotide polymorphism rs1581492 at 7q22.1 to be strikingly associated with EAS levels (P ≤ 2.49 × 10(-78)), and this result was replicated in KORA (P = 2.12 × 10(-9)). Mendelian randomization by rs1581492 genotype showed that EAS is unlikely to be causally related to CWP. Using an agnostic omics approach to focus on the association of CWP with body mass index, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes, which likely controls this response. This study suggests that steroid hormone abnormalities result from pain rather than causing it, and EAS may provide a biomarker that identifies subgroups at risk of CWP. [ABSTRACT FROM AUTHOR]