Current Projects
- Aetiology of Common Disease
- Eye Research
- Telomere and Ageing Research
- Osteoarthritis and Degenerative Disc Disease
- Osteoporosis
- Metabolism of Dietary Supplements and Medications
- Dermatology
- Pain Research
- Female Sexuality
Aetiology of Common Disease
Whole-genome transcriptomic profiling: A resource for the discovery of expression QTLs associated with common disease
Sponsord by: 
The Wellcome Trust
Date: 2007 - 2012
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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.
MolPAGE
Molecular Phenotyping to Accelerate Genomic Epidemiology
Sponsored by: 
The European Union FP6 programme
Date: 2004 - 2008
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This integrated project, being co-ordinated by the University of Oxford, is a 4-year project of 18 leading academic institutions, biotechnology and pharmaceutical companies. The DTR has provided, as a core resource, samples of blood, urine and abdominal fat from 20 DZ and 40 MZ highly phenotyped twin pairs as well as 10 obesity-discordant MZ pairs. The aims of the data analysis will be the estimation of components of variance and the discovery of discriminatory biomarkers.
EuroClot
Genetic Regulation of the End-Stage Clotting Process That Leads to Thrombotic Stroke
Sponsored by: The European Union FP6 programme
Date: 2005 - 2008
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Department of Twin Research is co-ordinating this 3 year EU Framework 6 Project which started in January 2005 with funding of €1,500,000 and 8 research partners from 5 European countries. EuroClot aims to unravel the genetic basis of thrombotic stroke leading to new diagnostics and drug targets. Over 3000 DZ and MZ twins have been sampled from European twin databases and genetic analyses are now fully underway with results due in early 2008.
DTR Role: As well as managing the running of the project, we are one of 8 twin registers providing data. Our cohort, which is predominantly female with an average age of 45, provided clinical and biochemical phenotypes from 1500 identical and 500 non-identical twin pairs as well as DNA and genome-wide linkage and association data.
ENGAGE
European Network for Genetic and Genomic Epidemiology
Sponsored by: 
The European Union FP7 programme
Date: 2008 - 2012
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The primary aim of ENGAGE is 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. The DTR is part of this large collaborative project, co-ordinated by University of Helsinki, which will be integrating data from over 80,000 genomewide association scans. The DTR will provide clinical, biochemical and genetic data from over 6000 UK twins.
DTR Role: Contributing clinical, biochemical, transcriptomic and genetic data from over 6000 twins as well as providing expertise in the genetic and epidemiological analyses.
Eye Research
International collaborative study of refractive and glaucoma endophenotypes
Sponsord by: 
US National Institutes of Health
Date: 2007 - 2010
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This international collaboration between the DTR, Professor Terri Young at Duke University in the USA, and Associate Professor David Mackey in Australia is aimed at genotyping 2000 twins from the TwinsUK cohort, and combining analysis with US and Australian twins to discover the genetic and environmental contribution to eye diseases such as glaucoma and myopia. It is becoming increasingly obvious that large collaborations will be needed to gain enough power to find genes in complex diseases.
MY EUROPIA
European Training in Myopia Research
Marie Curie Research Training Network
Sponsored by: The European Union FP6 programme
Date: 2006 - 2009
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The aim of the proposed genetic study using twins is to identify causal genetic variants responsible for variation in myopia by a further detailed study of our cohort in whom we have shown linkage loci on a genome-wide scan and linkage to the PAX6 gene region. In particular, this study aims to fine-map and identify genetic variants in two of our linkage regions with evidence of replication (11q23-24 and 3q26) using state of the art methods.
A unique aspect of the research training in this RTN will be that the training is for physicists, computer science students and engineers in biological techniques. On the other hand biology and medical students will have and introduction to the technological aspects, in addition to the cutting-edge and more specialized training in the particular topics of their projects.
The Genetics of myopia and refractive error: analysis of highly significant linkage loci
Sponsord by: The Wellcome Trust
Date: 2006 - 2009
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Refractive error is a common, easily and accurately measured, quantitative trait that is highly heritable, making it an ideal condition to study in an unselected, population-based set of sibling pairs, which is available using the TwinsUK registry. The prevalence of myopia is rising rapidly, and is associated with significant morbidity in those highly affected. We have previously demonstrated a high heritability for refractive error (0.85) in a classical twin study using a total of 506 MZ and DZ pairs, and published the first genome-wide linkage analysis of this common trait, with 5 loci showing highly significant linkage. The highest linkage peak (LOD 6.1) was on chromosome 11p13, and in a tagged-SNP study we demonstrated significant linkage but not association in the vicinity of the PAX6 gene. In a replication study, we have confirmed another of our significant linkage loci at chromosome 3q26. Fine-mapping of chromosome 11 has shown a consistent linkage locus at 11q23-24, which exactly coincides with a myopia locus found in an Ashkenazi family study. We propose to examine further the role for these two promising genomic regions in myopia development, as well as further studying PAX6, by fine-mapping the genes and neighbouring regulatory regions using polymorphic microsatellite markers and a dense sets of SNPs in an expanded cohort of 500 DZ twin pairs. We will replicate any results found using two independent samples of MZ twins and unrelated individuals.
Dissecting the Genetics of glaucoma and its risks factors using a twin study
Sponsored by: 
The Guide Dogs for Blind
Date: 2006 - 2008
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Glaucoma is a complex disease, causing considerable visual impairment, with several genetic and environmental risk factors. Discovery of genes involved in glaucoma is difficult, but careful analysis of risk-factors such as intraocular pressure and the optic disc measurements allows better refinement of the disease picture. We propose a twin study to establish which features are most heritable, something twin studies are ideally suited to, and to use the information to perform a genome-wide search for susceptibility hot-spots on the human chromosome.
The Molecular Epidemiology of age related cataract
Sponsored by: The Guide Dogs for Blind
Date: 2005 - 2008
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In this application, we will refine our search for susceptibility genes for cataract by performing a combined linkage and association study on 3 key chromosomal regions of an expanded cohort of 500 pairs from our unique twin study; most twins have already been accurately measured for cataract and several key risk factors. Our methodology is innovative for its use of twins to identify cataract-causing genes. Our research will have considerable impact on understanding the causes of this under-researched but major blinding condition - leading to potential new diagnostics and treatments.
Telomere and Ageing Research
Exploration of genes within QTL responsible for age related telomere variation in healthy female dizygotic twins
Sponsord by: The Wellcome Trust
Date: 2006 - 2009
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Telomeres are protective structures located at the end of chromosomes. Their length is linked to oxidative stress and has been correlated with longevity and with some age-related diseases in humans. It is possible that telomere length and rate of shortening can be used to predict ageing and diseases associated with it. Thanks to Wellcome Trust Project Grant 074951 we studied telomere length using, to our knowledge, the largest panel of healthy individuals in the world.
In the previous project we:
- Determined that genes explain from 36% to 90% of the variation in telomere length;
- Identified significant regions in the human genome in which genes contributing to telomere length are likely to reside.
Genetics of ageing: The genetic and environmental determinants of ageing in women
Sponsord by: The Wellcome Trust
Date: 2007 - 2012
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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. The twin study design will allow determination of heritability of the traits, genetic correlations between traits as well as genetic associations with existing genotype information. Sub-studies using the discordant identical twin model will be used to validate and confirm the results, as well as enabling us to adjust for genetic factors in the analysis.
- Cardiovascular: Systolic and diastolic blood pressure and total cholesterol
- Muscle: Body composition, Muscle mass using Hologic QDR 4500/w DXA
- Bone: Bone Mineral Density at hip, spine and whole body
- Respiratory: Lung volumes (FEV1, FVC) from vitalograph
- Vision: Cataract assessment (Scheimpflug lens photograph), Retinal vascular caliber (retinal photograph)
TwinsUK Genetic Epidemiology Resource
Sponsord by: The Wellcome Trust
Date: 2006 - 2011
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This project aims 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. We plan to ensure that the resource is investigated as thoroughly as possible, answering specific questions in a variety of fields, using well-designed studies in a cost-effective manner. In addition to maintaining and studying the existing phenotypes, the following will occur:
- Collection of new and longitudinal phenotypes eg. adipose tissue, eye data, inflammatory markers
- Linkage study and statistical analysis on 2,500 pairs
- Maintenance and consolidation of twin resource
- Extending the use of the database and website development
Osteoarthritis and Degenerative Disc Disease
TREAT~OA
Translational Research in Europe – Applied Technologies for Osteoarthritis
Sponsored by: The European Union FP7 programme
Date: 2008 - 2012
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Department of Twin Research is co-ordinating this new FP7 large collaborative project comprising 10 core European trans-disciplinary partners and 9 non-core partners including Japan, China and the US. TREAT~OA will address the need for better treatment and diagnostics for osteoarthritis utilising a worldwide resource of 28,000 OA phenotyped subjects with available genome-wide association scan data. To find out more visit http://www.treatoa.eu/
DTR Role: As well as providing scientific and project management support to this large collaborative project, the DTR will be supplying clinical and genetic data from over 2000 individuals from the Twins UK Registry as the core discovery panel and the Chingford Longitudinal cohort for replication. Recent published papers have reported on a number of new and replicated candidate genes for OA and this will be taken further over the next 5 years.
Genetic markers for susceptibility of osteoarthritis of the knee and hip
Sponsord by: 
The Arthritis Research Campaign (ARC)
Date: 2007 - 2008
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Osteoarthritis (OA) is the most common musculoskeletal disease in the UK, in large part determined by genetic factors. Identifying individuals at high genetic risk of knee or hip OA can help target existing therapies, investigate novel therapies and better understand modifiable environmental risk factors. Using data from 12 genes to compute the genetic risk of knee OA we have defined subsets of women at much increased risk of knee OA but the level of risk prediction appears to be different in men and has not been investigated for hip OA. We will recruit a new and independent large cohort of knee and hip OA cases to study 20 genes (including the 12 mentioned above) implicated at least twice with knee and/or hip OA risk. This will enable the discovery of optimal combinations of genetic variants to identify men and women at very high risk of knee or hip OA.
The ArcOGEN Consortium
Sponsord by: The Arthritis Research Campaign (ARC)
Date: 2007 - 2012
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Osteoarthritis is the most common form of arthritis and has a huge clinical and economic impact. The disease has a complex aetiology but genetic factors play an important role in pathogenesis. Identification of the loci that predispose to OA susceptibility will lead to a much better understanding of the cause of the disease as well as identifying new molecular targets for therapeutic intervention. Alleles that predispose to OA could also be used, in individual cases, to determine prognosis and the response to surgical or drug treatments. Recent advances in human molecular genetics coupled with the HapMap project and the development of relatively low cost high-throughput genotyping platforms provides us now with an opportunity to comprehensively search the whole genome for OA risk alleles. The aim of this proposal is 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. Our application is timely, in that it exploits the latest developments in the genetics of complex traits, and is unique, in that it represents the first genome-wide association scan for this common arthritis. The idea and design of the study originated at the Department of Twin Research.
Longitudinal Study of Lumbar Disc Disease: Natural History, Genetic Influence and association with inflammation and telomere length
Sponsord by: The Arthritis Research Campaign (ARC)
Date: 2006 - 2009
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Lumbar disc disease (LDD) is a feature of spine osteoarthritis (OA), is common and increases with age, yet it remains poorly understood. There is evidence that cross-sectional LDD is highly genetic. We will determine whether progression of LDD is also genetically determined using twins with pre-existing baseline scans obtained 10 years ago and follow-up scans. In addition white blood cell telomere length, as a marker of oxidative stress, will be analysed. The results will shed light on the biology underlying progression of LDD leading to future studies which will ultimately reveal novel therapeutic targets.
Telomere length, inflammatory mediators and osteoarthritis: the Chingford Study
Sponsord by: The Wellcome Trust
Date: 2006 - 2009
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Telomere shortening is implicated in cellular senescence. We hypothesize that rate of telomere loss explains variation in biological ageing above and beyond chronological age. Telomere length has been related to longevity and, with less certainty, to cardiovascular risk and dementia in humans. It is unclear, however, how telomere dynamics might account for physiological changes associated with ageing. The overall goal of this proposal is to explore relationships between telomere loss and different domains of ageing measured longitudinally in a cohort of women who have been studied in great detail. Participants of the Chingford cohort, currently aged 60-79, were first seen in 1989 and have been examined at least bi-annually since, with multiple repeated measurements of DNA and phenotype across a range of ageing domains. Participants will be re-characterised for the original as well as additional phenotypes that are known to correlate with age. The domains include detailed information on rates of change over 6-15 years of musculoskeletal, lung and cardiovascular disease, cognition and metabolic factors. The age-related traits will be correlated with rates of change in telomere length over time. The study will provide unique data on the validity of using parameters of telomere dynamics as indicators of biological ageing across a spectrum of traits and will explore their potential as predictive markers of ageing-related diseases. To find out more visit http://www.chingfordstudy.org.uk/
The Genetic Epidemiology of Degenerative Disc Disease
Sponsord by: The Wellcome Trust
Date: 2007 - 2012
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This is a novel approach to explore the genetic factors associated with lumbar degenerative disc disease. It uses healthy volunteer cohorts from TwinsUK, Rotterdam and others having spinal imaging for both cross-sectional and longitudinal analysis of this complex phenotype. Preceding work by this group and others has already begun to identify novel genetic determinants in osteoarthritis and degenerative disc disease. The main aim of the fellowship is to further the understanding of the genetic influences on degenerative disc disease (DDD). King’s College London has agreed to create a tenured position for Dr Williams following the expiring of her WT fellowship.
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
Sponsord by: The Arthritis Research Campaign (ARC)
Date: 2006 - 2011
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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. To find out more visit http://www.chingfordstudy.org.uk/
Osteoporosis
GEFOS
Genetic Factors for Osteoporosis
Sponsored by: The European Union FP7 programme
Date: 2008 - 2012
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This FP7 medium scale collaborative project funded for 5 years started early 2008. GEFOS, co-ordinated by Erasmus Medical Center, proposes to identify novel genes and pathways important in osteoporosis, through the integration and combined analysis of existing GWA scans and to confirm and validate these findings in the extended GENOMOS study group (n>100.000 subjects). The DTR will be supplying clinical, biochemical and genetic data for twins as well as performing genetic and epidemiological analyses.
DTR Role: To provide the twin GWAS as a discovery sample and meta-analysis as well as a wealth of intermediate phenotype bone data.
Genetic basis of variation in response to dietary supplements
Sponsored by: 
The Chronic Disease Research Foundation (CDRF)
Date: 2007 - 2010
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Aim: To identify genetic variants that influence inter-individual variability in response to supplementary dietary compounds including vitamins and minerals.
Dermatology
Skin ageing and naevi expression in relation to telomere length and vitamin D metabolism
Sponsored by: The Chronic Disease Research Foundation (CDRF)
Date: 2007 - 2010
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To assess the potential relationship between skin ageing, naevus counts, telomere length in white cells and melanocytes and Vit D metabolism.
Pain Research
The Genetic Epidemiology of Pain Perception
Sponsored by: 
Pfizer
Date: 2007 - 2009
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A twin study of pain perception that is designed to understand the importance of genetic and environmental factors in determining why people respond differently to pain.
Female Sexuality
Genetic Epidemiology of Female Sexual Dysfunction (FSD)
Sponsored by: Pfizer
Date: 2007 - 2010
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The identification of biomarkers and key genes showing novel neuronal and hormonal pathways that may be involved in FSD will be the aim of this twin study with the aim of providing new therapeutic targets and insights.