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Past Projects

1997-1999

Identification of novel genetic loci mapping to chromosome

This study led to the identification of genetic factors associated with Osteoarthritis and Osteoporosis and was responsible for identifying potential genetic factors associated with this condition.

1997-2002

Collection of biological materials from knee Osteoarthritis case.

The collection of biological materials from knee OA cases has enabled a multitude of research papers to be published in the field of OA that cover all aspects of the field, from the early clinical manifestations of the disease, to the revelation of the environmental and genetic causes of OA.

2002-2005

Twin migraine study

Certain conditions characterised by blood vessel constrictions (such as hypertension, migraine, Raynaud’s phenomenon and coronary artery disease) have been found to be related in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to show that these conditions are linked through a common underlying genetic propensity to blood vessel spams.

2007-2010

The genetic basis of variation in response to dietary supplements

This research has resulted in the identification of the genetic basis for adverse drug reactions and individual responses to vitamin supplementation.

2012-2015
Funding for DNA collection in fibromyalgia. 

A DNA resource from 2000 people having chronic widespread pain (CWP) will be constructed and then genomic/epigenomic pain candidates identified in twins will be validated in patients.

2013-2016

Funding for twin recruitment and DNA collection, in Rheumatoid Arthritis. 

Recruit and examine new twin pairs with at least one member of each pair having RA, in collaboration with patients associations and clinical rheumatologists in the UK, to perform DNA and RNA extraction and store blood samples for study of RA.

2016 - 2021

The Urinary Microbiome and its Relation to Morbidity in Older People

 

Urinary symptoms and signs in the elderly are closely associated with frailty, delirium and distress, but our understanding of the relationship of the urinary flora and morbidity is currently very limited, leading to overtreatment with antibiotics. This study has the potential to re-write textbooks, which have propagated a false dogma that the urine is sterile, and create the first step to understanding the implications for the host of different urinary patterns of microbes.  First cataloguing the populations of microbes in older people is essential at this stage of the science, to generate hypotheses that would be testable experimentally.  In the shorter term, easy-to-obtain midstream urine analysis could also be used to stratify the management of older adults. 
 

2017 – 2024

Exploring the cardio-metabolic health-associated with the faecal metabolome.

 

The goal of this project is to increase our understanding of how molecules produced by microbes influence our health.   This study aims to identify the biochemical signature of cardio-metabolic health in the faecal metabolome and to determine its links with diet, the gut microbiome and host genetics. An understanding of these links offers a unique target for intervention to prevent and reverse chronic disease. This is a totally novel proposal and we are the first group in the world to use faecal metabolites as health indicators.

2017 – 2022

A statistical framework for personalised nutrition recommendations based on genetic and anthropometric data.

 

This project will explore the genetic influences on a healthy diet, impact on disease and ageing.  The intended outcome is the identification of patterns in the genome that can predict responses to diet to improve health.  The study will investigate the relationship between genetic factors, dietary habits, anthropometric traits and cardio-metabolic traits, with the aim of proposing personalised nutrition recommendations and minimising the risk of obesity.

2018 – 2023

Influence of the gut microbiome on inter-individual differences in blood pressure at fasting and in response to a combined glycaemic and lipaemic test meal challenge.

 

The object of this study is to assess the relationship between the gut microbiome, fasting and post-prandial blood pressure (BP). The study aims to identify bacterial species and pathways involved in this process using ambulatory BP measures and to assess how they interact with diet and age. The goal is to design personalised dietary guidelines and interventions aimed at treating and preventing hypertension based on the composition of the individual's gut microbiome. 

2019 – 2022

Novel computational and multivariate approaches to exploring diet-microbiome relations

The object of this study is to determine the contribution of host genetic, diet and the gut microbiome on fat accumulation. Twins are ideal for dissecting the contribution of individual genetic and environmental influences on human traits. However, there is still a lack of good models which allow the separation of diet and microbiome effects to study obesity-induced cardiometabolic diseases. The study will use food frequency questionnaires (collected at three-time points) and 24h diet records coupled to shotgun metagenomics profiling of the gut microbiome of 1000 volunteers from the TwinsUK cohort. This ambitious proposal will tackle this issue by applying newly developed food classification methods to permit a more comprehensive understanding of the impact of long and short term-food choices on the gut microbiome. These results will be used to improve our understanding of how the microbiome impacts visceral fat.   

1997-1999

Identification of novel genetic and environmental influences in osteoporosis

This study helped to reveal the genetic and environmental risk factors that influence osteoporosis, osteoarthritis and back pain. Understanding the underlying causes of these conditions is a crucial step in developing new therapies for these common conditions of ageing.

1998-1999

Osteoporosis- genetic susceptibility

This study searched for the genetic factors associated with Osteoporosis in an affected family and was responsible for identifying potential genetic factors associated with this condition.

2003-2006

Genetic epidemiology of cognitive behaviour

This study focused on how effective self-report memory tests are – which had previously received little attention. As a result of this study, it was found that heritability estimates ranged between 37% and 64% for contentment (e.g., reporting to worry about one’s memory) and approximately 45% for ability (e.g., reporting a tendency to forget keys). These tests were found to be extremely useful in examining memory functioning in large-scale population studies and will help similar future cognitive studies. The study also identified a potential genetic region for forgetfulness and also showed that large-scale gene discovery studies are possible with self-report memory questionnaires.

2007-2010 

Skin ageing in relation to telomere length and vitamin D metabolism

This study showed, for the first time, that ‘moley’ people who have a slightly increased risk of melanoma may, on the other hand, have the benefit of reduced susceptibility to age-related diseases such as heart disease or osteoporosis.

2011-2012

Understanding the genetic predisposition to migraine-a meta-analysis approach 

Migraine is the most common brain disorder; however the molecular mechanisms giving rise to them are poorly understood. The migraine consortium involved research into the genetic determinants of migraine and its subsets, migraine with aura and migraine without aura.

2015-2016 

Investigation of microbiome in rheumatoid arthritis in discordant monozygotic twins.

There is good evidence that rheumatoid arthritis (RA) is influenced, and perhaps even caused, by alterations in the gut microbiome. The microbiome is, in turn, influenced by the host organism genotype. Thus twins are the perfect experimental model in which to study the influence of gut microbiome in RA.

2016 - 2020

Biotwincot – Biology of twins from conception to toddler
 

Foetal programming – the adaptive responses of the foetus to a variety of environmental cues, and consequences of the mismatch between the prenatal and postnatal environments – can permanently shape the body’s structure, function, and metabolism and contribute to adult disease. The influence of the microbiome – the microorganisms living in and on a mammalian host - and how it is acquired in humans is poorly understood. 

 

This project addresses this deficiency by studying the human microbiome longitudinally during early development, from the earliest possible time during pregnancy, using nature’s controlled experiment, twins. The project aims to pilot the collection of the microbiome and additional biological samples from 10 mothers and twin-pairs at four time-points during the first year of life, to assess the feasibility to support a major project of this kind.

2017 – 2022

Utilising omega 3 and fibre to improve metabolic health: a proof of concept nutritional intervention study targeting the gut microbiome.

 

The growing importance of gut microbiota in all aspects of human health is clear.  Unlike our genomes, this is potentially highly modifiable and tightly related to metabolic and immune efficiency, energy and fatty acid metabolism, and satiety hormones. We have recently shown that serum levels of omega-3 fatty acids correlate with higher microbiome diversity, and are linked to lower inflammation of the gut. The study will measure faecal metabolites relevant to fatty acid metabolism (short-chain fatty acids) and the abundance of microbial species linked to higher or lower inflammation and immune cell phenotypes, to unravel the link between inflammation, diet and metabolic syndrome. There is a real lack of good diet intervention studies in this field and if successful this trial will pave the way to funding a wide variety of other diet intervention studies. 

2018 – 2020

Gut microbiome modulation of fasting glucose homeostasis and postprandial glycaemic response in TwinsUK and PREDICT: towards personalised diet for healthy ageing.

 

This highly novel study will pioneer the identification of a personalised diet specific to an individual’s microbiome and responses to diet, using a bioinformatics approach.  Insulin resistance is highly prevalent worldwide and has strong associations with many age-related conditions. There is also evidence that age and decreased diversity and increased fragility of the gut microbiome, play an important role in insulin resistance. Preventive strategies have focused on general dietary guidelines, to reduce caloric intake or focus on the glycaemic index of food. The glycaemic response to food shows high variability between individuals and the microbiome is now recognised as a crucial element explaining this personal uniqueness. This study aims to identify bacterial species and pathways involved in fasting and postprandial glucose homeostasis and how they interact with diet and age. Our results will help to design personalized dietary guidelines and interventions aimed to prevent insulin resistance based on the individual’s age and on their gut bacterial community. 

2020 – 2022

TwinsUK Covid-19 Research Program

 

The Covid-19 pandemic is a major public health emergency, and a rapid experiment in twins can make a huge difference in understanding the disease and finding ways of preventing it. TwinsUK is an internationally unique resource with ~7000 actively participating twin pairs spread around the UK.  Apart from being twins, they are representative of the UK population overall. 

Using the TwinsUK cohort gives the program considerable advantages over newly recruited cohort or case-only studies because (a) they are twins, enabling assessment of heritability and controlling for environmental effects in genetic studies, (b) they are nationally distributed and community-dwelling, so will give an accurate national picture of the pandemic, (c) they are extensively characterised already, so many analyses will be possible with minimal additional phenotyping costs, (d) the TwinsUK and GSTT-KCL NIHR BRC are well set up to run a study of this magnitude and (e) The Wellcome Trust and MRC already support the core of the cohort so may expand on this study longer-term with the development of a Covid-19 Bioresource.

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