TwinsUk

TwinsUK
Founder(s)	Professor Tim Spector
Established	1992 (1992)
Staff	50
Location	London, UK
Address	St Thomas’ Hospital Campus 3rd & 4th Floor South Wing Block D, Westminster Bridge Road London SE1 7EH
Website	www.twinsuk.ac.uk

TwinsUK was set up by Professor Tim Spector in 1992 using grant funding from the Wellcome Trust and Arthritis Research Campaign (ARUK) and it is currently based at the Department of Twin Research, King's College London. Its initial main aim was to investigate the incidence of osteoporosis and other rheumatologic diseases in a small cohort of several hundred monozygotic (identical) twins. Since then the registry has expanded in number and areas of research covered. It currently comprises a total of 12,000 identical and non-identical twins - with an approximate 50:50 split between each zygosity from right across the UK with ages between sixteen and ninety eight.^[1]

The data collected from the TwinsUK cohort has enabled multiple collaborations with over 60 groups worldwide and the publication of 600 research papers. The database has an extensive range of phenotypes obtained from twins many of whom have attended the Department for clinical visits over the last eighteen years. The TwinsUK cohort is increasingly used as a resource by other researchers who are encouraged to request data from the easily-searchable database online.^[2]

History

The Department of Twin Research & Genetic Epidemiology was set up by Professor Tim Spector, Consultant Rheumatologist in 1992 using grant funding from the Wellcome Trust and Arthritis Research Campaign (ARUK). Its main focus was to look at the incidence of osteoporosis and other rheumatologic diseases in several hundred monozygotic (identical) female twins. The Department then joined the Division of Genetics and Molecular Medicine, King's College London on 1 September 2006. Since then the Department has expanded greatly both in areas of research as well as in the number of twins recruited.It now encompasses a registry with a database of 12,000 identical and non-identical twins from right across the UK with ages between sixteen and ninety eight. Female twins continue to predominate and overall the mean age is in the mid fifties. It is now the UK’s only adult twin registry and the most clinical detailed in the world.^[3]

It is now the UK’s only adult twin registry and the most clinical detailed in the world. The breadth of research the cohort has supported has expanded over the years to cover the genetics of a wide range of common complex traits, and the TwinsUK cohort is now probably the most genotyped and phenotyped in the world. Recently genome-wide association studies have identified over 400 novel gene loci in over 30 disease areas including osteoporosis, osteoarthritis, melanoma, baldness, and telomere length from TwinsUK data. Current research covers the genetics of metabolic syndrome and cardiovascular disease, musculoskeletal system, ageing and sight. TwinsUK currently has programmes of research examining rare variants via whole-genome next generation sequencing (UK10K project), gene expression in multiple tissues (MuTher study), Epigenetics (EpiTwin project) and metabolomics, all to continue the study of how genes and environment interact to cause common age-related diseases, and to examine “healthy ageing”.

Research

As well as carrying out research activity in-house, TwinsUK provides data and samples to the scientific community on an open-access basis. Over the years, around 600 scientific papers have been published using data collected and held by TwinsUK. Some of the research areas include Rheumatic Diseases, Genetics, Ageing (which involves determining the rates of ageing by common genetic and environmental factors, identifying biomarkers of ageing using whole transcriptome sequencing and how closely changes at one organ or tissue correlate with overall physiological deterioration)^[4] and Epigenetics. Their research revolves around: Omic tools, diseases and ageing.^[5]

Epigenomics

Epigenetic mechanisms, such as DNA methylation, can be subject to genetic, environmental and stochastic influences, and can have important downstream effects on gene expression regulation, normal development and disease. TwinsUK's research focuses on the epigenetic basis of human health and disease in twins, as well as on understanding the factors driving epigenetic variation.^[6]

Pain

The pain group of TwinsUK is working on various aspects of clinical chronic pain-syndromes including musculo-skeletal pain such as fibromyalgia and low back pain; and visceral pain including unexplained pelvic pain and irritable bowel syndrome. In addition, they have obtained objective pain sensitivity measures on the Twins through quantitative sensory testing (QST). There is also an interest in the behavioural and psychological aspects of pain.^[7]

Projects

TwinsUK runs or contributes to several programmes of research examining rare variants via whole-genome next generation sequencing: UK10K project, gene expression in multiple tissues: MuTher study and Epigenetics: EpiTwin project in conjunction with the BGI all to continue the study of how genes and environment interact to cause common age-related diseases, and to examine “healthy ageing".

Epigenetics

EpiTrain - The scope of EpiTrain is to develop a broad scale understanding of epigenetic processes in common disease. The goal of the proposed network is to provide open training facilities for the next generation of researchers in the field of medical epigenetic research across a wide spectrum of research and develop synergies between the different research disciplines.

EpiTwin - The EpiTwin project, in collaboration with the Beijing Genomics Institute (BGI), is one of the most ambitious large-scale projects in Human Genetics. The aim of this project is to capture the subtle epigenetic profiles that mark the differences between 5,000 twins on a scale and depth never before attempted (funded by the European Research Council).^[8]

Ageing

Genetics of ageing: The genetic and environmental determinants of ageing in women - To test whether common genetic and environmental factors that determine rates of ageing across different organ systems. The longitudinal nature of the study following women through middle age with up to 18 years follow-up will enable us to address how closely changes at one organ or tissue correlate with overall physiological deterioration (funded by The Wellcome Trust)

Creation of Chingford cohort resource and maintenance of data collection & analysis of a 20 year longitudinal cohort of musculo-skeletal disease in the general population: The Chingford study - Started in 1989 The Chingford Study recruited women aged 45–65 as part of a longitudinal study to examine natural history and risk factors for a number of musculo-skeletal diseases. The study forms a unique longitudinal population study and in the 18 years since its inception the data collected have contributed to the widening knowledge of the natural history of osteoarthritis and osteoporosis (funded by The Wellcome Trust).

EuroBATS - Co-coordinating this 3 year EU Framework 7 Project which started in January 2011 with funding of €3,000,000 and 4 research partners from 3 European countries (funded by The European Union FP7 programme).

Age-related hearing impairment - Using the latest techniques to study the genome and epigenome in twins of all ages to understand further the genetic contribution of this common age-related trait (funded by The Royal National Institute for Deaf People (RNID)/Age UK).^[9]

Genetics

Whole-genome transcriptomic profiling: A resource for the discovery of expression QTLs associated with common disease - Its main aim is to annotate regulatory elements across the human genome and identify cis and trans acting eQTL that are specifically associated with expression phenotypes in lymphoblastoid cell lines (LCLs) and subcutaneous abdominal fat tissues and test them as candidate polymorphisms for association with obesity-related phenotypes in a series of large scale genetic association studies (funded by The Wellcome Trust).

ENGAGE - To translate genetic and phenotypic data emerging from large-scale research studies in genetic and genomic epidemiology for future clinical advances. Early studies will concentrate on metabolic and cardiovascular phenotypes (funded by The European Union FP7 programme)

TwinsUK Genetic Epidemiology Resource - To build on the existing TwinsUK resource. The previous Wellcome FGI funded development of the twin resource and the creation of a website and open access by researchers to limited twin data (funded by The Wellcome Trust).

TREAT-OA - Co-ordinating a 5 year EU Framework 7 Large Collaborative Project (HEALTH-F2-2008-00) which started in January 2008 with funding of €11,924,000 and 10 research partners from 6 European countries (funded by Funded by The European Union FP7 programme)

The ArcOGEN Consortium - to conduct a genome-wide association study for OA susceptibility alleles in a large collaborative study of 8000 OA cases and 6000 controls involving 5 UK centres; we will scan the human genome for associated variants using a cohort of 4000 OA cases and 3000 controls and then replicate associated loci using an independent cohort of 4000 cases and 3000 controls. The idea and design of the study originated at the Department of Twin Research (funded by Funded by The Arthritis Research Campaign).

The Genetic Epidemiology of Degenerative Disc Disease - To use a number of different approaches to unravel the genetic epidemiology of intervertebral disc degeneration (funded by The Wellcome Trust).

GEFOS - to identify novel genes and pathways important in osteoporosis (funded by The European Union FP7 programme).

Genetics of common eye diseases - This project continues the Department’s interest in understanding the genetic epidemiology of common eye problems, in particular myopia, age-related cataract and glaucoma, and currently dry eye disease (Funded by National Institute for Health Research).

Rare variants in glaucoma: a whole-genome sequencing study - analyzing with respect to quantitative phenotypes associated with glaucoma, namely intraocular pressure, optic disc size and cupping, and central corneal thickness (funded by Fight for Sight).

UK10K - To enable researchers in the UK and beyond to better understand the link between low-frequency and rare genetic changes, and human disease caused by harmful changes to the proteins the body makes (funded by The Wellcome Trust.^[10]

The role of mitochondria in common disease - Aims to identify the genes responsible for these linkage signals and further fine map the association signals already identified (funded by Medical Research Council).^[11]

See also

• Twins Early Development Study

References