We have taken an exciting step forward in our mission to advance health research with the launch of the AdiProPlus Biopsies study. This study aims to uncover the role of fat tissue – known as adipose tissue – in the development of metabolic diseases such as type 2 diabetes, cardiovascular disease, and age-related health conditions. We recently had our first twin pair come in to participate in the study, marking an important milestone in this research.
Understanding the Role of Fat in Metabolic and Age-Related Diseases
Adipose tissue plays a critical role in regulating metabolic processes in the body, yet the molecular signals it sends and its genetic regulation remain poorly understood. By collecting small skin and fat tissue samples through a procedure called a biopsy, researchers hope to gain invaluable insights into how genes influence changes in fat tissue and how these changes contribute to the development of conditions like type 2 diabetes, cardiovascular disease, and ageing-related health complications.
Professor Kerrin Small explained:
“Our goal is to deepen our understanding of adipose tissue and its links to conditions like type 2 diabetes, cardiovascular disease, and ageing. This knowledge could eventually lead to better prevention and treatment strategies for a range of metabolic and age-related diseases.”
What the Study Involves
Participants undergo a careful screening process to ensure they meet the study’s safety criteria. Once recruited, participants will visit our clinic, complete questionnaires, and engage in a discussion about the procedure with our clinic team.
The biopsy itself is quick and minimally invasive, involving the collection of an 8mm circular sample of skin and fat tissue from the lower abdomen. Participants can also opt to provide an additional sample from the gluteus area. The procedure is performed under local anaesthetic, and participants are provided with aftercare instructions and options for suture removal either through their GP or at the TwinsUK clinic.
First Twin Pair’s Experience
The first twin pair to take part in the study shared their thoughts about being part of TwinsUK.
“We’ve always been interested in experimental science, and when we heard about the biopsy study, we were keen to sign up and learn more about the tests and results. This felt like a natural next step for us. The ageing aspect of TwinsUK that twins are participating in is incredibly valuable – not just for twins, but for the wider population – and we want to contribute in any way we can.”
The twins described the biopsy as a smooth and straightforward process.
“Everybody has been brilliant – they explained everything clearly, which helped us understand what to expect. They were also incredibly supportive, allowing us to go at a pace that suited us, which was lovely. The process was easy, painless, and, most importantly, for a great cause – advancing research.”
A new study reveals the impact of low-level exposure to heavy metals such as mercury on skin tissue.
A study led by researchers at King’s College London, published in Science of The Total Environment, has revealed how even low levels of mercury exposure can disrupt critical molecular processes in the body, particularly in the skin.
Researchers analysed data from over 800 British female twins from the TwinsUK cohort, measuring the levels of three heavy metals – mercury, selenium and lead – in the blood. They then examined whether the levels of these metals were linked to gene expression in three key tissues: blood, fat (adipose) and skin.
Unlike high-dose studies, this research explored the molecular effects of subtle, sub-toxic heavy metal exposure, offering a more realistic understanding of how day-to-day exposure to environmental pollutants impacts the body in the general population.
Tissue-specific impacts
One of the key findings of the study was the strong association between mercury levels and changes in molecular processes in skin, whereas no such effects were observed in blood or adipose tissue. The changes in skin tissue were most pronounced in genes linked to mitochondrial function. Mitochondria, often referred to as the “powerhouses” of the cell, play a crucial role in energy metabolism.
Professor Kerrin Small explained:
“Our results are very consistent with what’s known about the biological effects of high, toxic exposure to mercury. But what we’re showing here is that sub-toxic mercury exposure leaves a clear molecular signature in the general population,” said Professor Kerrin Small, Professor in Genomics at King’s and senior author of the study. “This demonstrates that exposure to these pollutants has effects even at levels far below what is considered safe.”
The study didn’t explore the potential health impacts of these molecular changes, but the findings highlight the importance of exploring low-level pollutant exposure and its cumulative effects over time. The findings also suggest that multi-tissue analysis could be a crucial tool for understanding the broader biological impacts of pollution.
Dr Alan Hodgkinson, Senior Lecturer at King’s and co-author of the study, explained:
“Mercury exposure disrupts mitochondrial function, and skin may be particularly vulnerable to exposure due to its high energy demands and direct exposure to the environment. We have seen a link with mercury levels and molecular changes in the skin, but the health impacts of this remain unclear, making it an important area for future research.”
Building on this research, the team plans to expand the study to a larger cohort, aiming to explore additional molecular markers in the body linked to heavy metal exposure.
We’re excited to announce that a study building on research from TwinsUK has been shortlisted for the Versus Arthritis Research Highlight of the Year award. This research explores how our gut and saliva microbiomes could revolutionise treatment for rheumatoid arthritis (RA).
Transforming RA Treatment
Rheumatoid arthritis is a chronic autoimmune condition that causes inflammation, pain, and stiffness in the joints. Treatments often involve disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate or sulfasalazine, which can ease symptoms and slow disease progression. However, finding the right DMARD often involves trial and error, requiring weeks to assess whether a treatment is effective.
Our researchers at TwinsUK aimed to address this challenge by uncovering how the microbiome – the community of bacteria, viruses, and fungi living in our gut and saliva – might predict a patient’s response to DMARDs.
Key Findings
The study analysed data from 144 people newly diagnosed with RA who had not yet started DMARD treatment. Participants provided stool and saliva samples at three time points:
Before starting DMARDs,
Six weeks after starting treatment,
Twelve weeks after starting treatment.
The team found that the microbiome profile before treatment could predict whether a patient would respond well to DMARDs. They also observed that DMARDs appeared to rebalance gut bacteria, which may explain their effectiveness in some patients.
The findings were compared with long-term DMARD users, revealing further changes in the microbiome over time.
Why Does This Matter?
This research marks a significant step toward personalised treatment for RA, where doctors could one day use a simple stool or saliva test to predict how a patient will respond to a specific DMARD. This would save patients from the frustration of trial-and-error approaches and allow healthcare teams to provide tailored care from the outset.
Additionally, the discovery that DMARDs might restore balance to the microbiome offers exciting potential for new therapies that directly target these bacterial communities to improve outcomes.
Thank you
While this work builds on research based on the TwinsUK cohort, the recruits for this study were patients from across the UK, recruited from rheumatology departments in numerous hospitals. We are incredibly grateful to all those who contributed to this study, as your involvement continues to drive research that improves lives and advances our understanding of complex diseases. We’re immensely proud of this work and thankful for your support.
A new study has revealed how our genes influence fat tissue and its role in health. Researchers from TwinsUK and their collaborators have created AdipoExpress, the largest-ever analysis of gene activity in fat tissue, using samples from over 2,300 people, including our TwinsUK participants. The findings could help explain why some people are more likely to develop conditions like type 2 diabetes and obesity and point the way to new treatments.
What Makes Fat So Important?
Fat, or adipose tissue, isn’t just for storing energy. It’s a busy organ that produces hormones, controls metabolism, and even helps manage inflammation. When fat doesn’t work properly, it can lead to serious health problems like diabetes and heart disease. This study focused on subcutaneous fat (the kind found under the skin) because it’s easier to collect samples from volunteers.
Key Findings
Mapping the Genetics of Fat: The researchers identified nearly 35,000 genetic signals that influence how genes work in fat tissue. This is more than twice as many as found in previous studies and shows how complex the genetic control of fat really is.
New Genetic Insights: Many of these signals weren’t in the main gene control regions (called promoters). Instead, they were further away, acting more like distant dimmer switches. These signals often fine-tune the activity level of a gene rather than simply turning it on or off. Despite their subtle effects, they frequently influence genes that play important roles in health.
Linking Genes to Diseases: By combining their findings with data from previous studies on health and disease (called genome-wide association studies or GWAS), the researchers identified over 1,800 genes that might affect traits like body fat distribution and diabetes risk. Including these additional genetic signals uncovered 46% more connections to disease than looking at primary signals alone.
Why This Matters
The researchers say this work highlights the importance of studying fat tissue to understand health and disease. Combining genetic studies like GWAS with RNA analysis – studying which genes are turned on or off in tissues – helps pinpoint the genes and tissues involved in diseases.
Adipose tissue plays a key role in managing metabolic health, and this study offers the largest map yet of how genetics controls its function. This has led to new discoveries about type 2 diabetes and how body fat is distributed – discoveries that weren’t possible before.
The researchers also point out how genetic control of gene activity in adipose tissue underlies how men and women store fat differently, and this can affect health in distinct ways. Our upcoming study, AdiProPlus, will specifically look at these differences where we will collect fat biopsies with a new focus on both male and female volunteers.
Next Steps
The findings from AdipoExpress are now publicly available here, allowing scientists around the world to use the data for further research. This open approach will speed up discoveries and help uncover how our genes shape our health.
Wednesday, 29th January | 1:00 PM – 8:00 PM | Governor’s Hall, Ground floor, south wing, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH
The London Microbiome Meeting is an annual in-person event, first held in 2014, designed to foster discussion, share knowledge, and stimulate debate on human microbiome research within London and beyond. This conference provides a comprehensive overview of the latest research findings and methodological advancements in the field.
This year’s focus is the intricate relationship between nutrition, aging, and the gut microbiome, with a special emphasis on how these factors shape human health. Attendees will have the opportunity to connect with leading microbiome experts and build a strong research network, drawing from institutions in London and around the world.
This is a ticketed event for researchers and clinicians only. Tickets available here.
There will be a poster session (apply here – application deadline 10th December).
Hosted by the Department of Twins Research and the Department of Nutritional Sciences,
Sponsored by Yakult.
Agenda
1:00 PM – 1:30 PM
Arrival and Welcome Drinks
1:30 PM – 1:40 PM
Opening Remarks
Prof. Claire Steves
Prof. Kevin Whelan
1:40 PM – 3:40 PM
Talks and Q&A Session
– Prof. Paul Cotter, Teagasc Food Research Centre
“Harnessing the potential of fermented food microbiome”
– Dr. Amrita Vijay, University of Nottingham
“The gut microbiome and metabolic health”
– Dr. Peter Rimmer, University of Bermingham
“FMT in early IBD; ready for prime time?”
3:40 PM – 4:00 PM
Break and Poster Viewing
4:00 PM – 6:00 PM
Talks and Q&A Session
– Prof. Lindsay Hall, Quadram Institute
“The gut microbiome in early life”
– Dr. Anjali Chander, King’s College London
“The role of Fusobacterium nucleatum in head and neck squamous cell carcinoma development and treatment outcomes”
– Prof. Debbie Shawcross, King’s College London
“Poo pills – a new paradigm in the treatment of liver disease”
6:00 PM – 6:10 PM
Closing Remarks
Prof. Kevin Whelan
6:10 PM – 8:00 PM
Drinks and Nibbles
Speakers
Prof. Paul Cotter, Teagasc Food Research Centre
Talk title: Harnessing the potential of fermented food microbiome
Bio: Prof Paul Cotter is the Head of Food Biosciences at Teagasc, is a Principal Investigator with the large Irish Research Centres, APC Microbiome Ireland, VistaMilk and Food for Health Ireland and CTO/co-founder of SeqBiome, a microbiome sequencing and bioinformatics service provider. He is a molecular microbiologist, with a particular focus on the microbiology of foods (especially fermented foods), the food chain, and of humans, as well as probiotics and postbiotics. Prof Cotter is the author of >400 peer-reviewed, was included in the Clarivate list of highly cited researchers for 2018-2023, received an honorary doctorate from the University of Antwerp in 2024, and is the Field Chief Editor of Frontiers in Microbiology.
Prof. Lindsay Hall, Quadram Institute
Talk title: The gut microbiome in early life
Bio: Prof Lindsay Hall is the Chair of Microbiome Research at the University of Birmingham, and she is also an affiliated Group Leader at the Quadram Institute and a Wellcome Investigator. Her lab’s research focus involves defining microbe/microbiota interactions during the early life developmental window. She also has a keen interest in bringing the magical world of the microbiome to life for public audiences and school children. She obtained a BSc in Microbiology from the University of Glasgow, a PhD in Microbiology and Immunology from the University of Cambridge, and was a postdoctoral fellow at University College Cork, Ireland (APC Microbiome Institute). She returned to the UK to take up a Senior Lectureship at the University of East Anglia before moving to the Quadram Institute. Prior to Lindsay joining the University of Birmingham, she was Chair of Intestinal Microbiome at the Technical University of Munich in Germany.
Prof. Debbie Shawcross, King’s College London
Talk title: Poo pills – a new paradigm in the treatment of liver disease
Bio: Debbie Shawcross is a Clinician Scientist and Professor of Hepatology and Chronic Liver Failure at the Institute of Liver Studies and James Black Centre, King’s College London. She works as a Consultant Hepatologist on the King’s Liver Unit with a specialist interest in hepatic encephalopathy, liver failure syndromes and the complications of cirrhosis. She joined the EASL [European Association for the Study of the Liver] Scientific Committee and Governing Board in October 2022 and was elected Vice Secretary General of EASL in June 2023. She is an advocate for high quality education and training in gastroenterology and hepatology having been a Health Education England London Gastroenterology Training Programme Director for 10 years, British Society of Gastroenterology (BSG) Mentor and an active member of the BSG Supporting Women in Gastroenterology. She is Chair of the BSG Research Committee.
Her research programme characterises the immunobiology of chronic liver failure focusing specifically on the gut-liver-brain axis in the context of the gut microbiome as a driver of immune dysfunction, inflammation and encephalopathy. She is leading the field in clinical trials of faecal microbiota transplantation (FMT) in Europe and is Chief Investigator of the NIHR-funded EME UK multicentre randomised placebo-controlled clinical trial of FMT (capsules) [PROMISE Trial] in patients with metabolic-associated and alcohol-related cirrhosis.
Dr Amrita Vijay, University of Nottingham
Talk title: Supplementing Health: Anti-Inflammatory effects of Nutrients and Foods
Bio: Dr Amrita Vijay is a Research Associate in Gut Microbiome and Metabolic Health at University of Nottingham. She completed her PhD at King’s College London, where she specialised in salivary and mucosal biology. She then pursued her postdoctoral research at the TwinsUK, Department of Twin Research and Genetic Epidemiology, King’s College London before moving to Nottingham where she currently works with Professor Ana Valdes, leading dietary intervention studies focussing on gut microbiome and metabolic health both in the UK as well as in India. Her current research focuses on observational and interventional studies on the role of nutrition, gut microbiome and metabolomics in relation to health and disease. Dr Vijay was awarded under the Nottingham Reward Scheme in recognition of her valuable contribution to research for 2020/2021.
Dr. Peter Rimmer, Consultant in Gastroenterology, QEHB, Honorary Senior Research Fellow, UoB
Talk title: FMT in early IBD; ready for prime time?
Bio: Dr Peter Rimmer is a consultant gastroenterologist at University Hospitals Birmingham and senior research fellow at the University of Birmingham. He has integrated his clinical and research practice to deliver early diagnosis for IBD patients whilst focusing on the characterisation of the pretreatment gut microbiome. He is a member of the clinical team at the Microbiome Treatment Centre within the University, with roles in the delivery of a Faecal Microbiota Transplantation service to the NHS for Clostridioides difficile treatment, but also for ongoing research studies in IBD and PSC.
Dr Anjali Chander, King’s College London
Talk title: The role of Fusobacterium nucleatum in head and neck squamous cell carcinoma development and treatment outcomes
Bio
Anjali is a final year PhD student based in the Centre for Host-Microbiome Interactions at King’s College London. She is supervised by Dr Miguel Reis Ferreira and Dr David Moyes. Her research focuses on exploring the impact of the microbiome on head and neck cancer treatment outcomes. Her area of interest is specifically looking at Fusobacterium nucleatum and its role in head and neck squamous cell carcinoma development and treatment outcomes.
Anjali completed her MBBS degree at King’s College London in 2013 in addition to undertaking an intercalated BSc in Physiology in 2010. This has been followed by gaining post-graduate clinical qualifications including Membership of the Royal College of Physicians and Fellowship of the Royal College of Radiologists. She is currently a senior specialty registrar (ST7) in Clinical Oncology, and has a strong interest in managing patients with head and neck cancers.
TwinsUK is excited to announce an expansion of our data contribution to the UK Longitudinal Linkage Collaboration (UK LLC). During the COVID-19 pandemic, TwinsUK joined forces with other population cohort studies to share data for vital COVID-19 research. Now, the UK LLC is growing beyond COVID-19 to enable broader research that links health, environmental, education, and administrative records, based on each study’s permissions.
TwinsUK has already contributed COVID-19 datasets and linked our members’ health and environmental records. Following consultation with our TwinsUK Volunteer Advisory Panel, we will now be contributing additional datasets and linking to participants’ education records in line with the preferences twins have set on their consent forms or earlier data linkage decision forms.
All data is securely held at the University of Swansea and managed by the University of Bristol, ensuring that it remains de-identified at all stages to protect privacy. Researchers who wish to use this data must apply, and only bona fide researchers working on health studies for public benefit will be granted access to TwinsUK data, after approval by the TwinsUK Resource Executive Committee.
“We’re pleased to be working closely with the UK LLC, enabling even more vital research into public health. This expansion allows us to work on critical questions beyond COVID-19, and fulfil the ongoing TwinsUK remit, helping our researchers to better understand how various factors influence people’s health throughout life.”
For more details on this collaboration and how your data is protected, please visit the UK LLC website.
We are excited to share that our study on X chromosome inactivation in systemic lupus erythematosus (SLE), led by Dr. Amy Roberts and her team, has been highlighted in Nature Reviews Rheumatology. The article, titled “Is X chromosome inactivation a cause or effect of SLE?”, shines a spotlight on the key findings from our study, which challenge long-standing assumptions about the role of X chromosome inactivation (XCI) in lupus.
The study, recently published in the Annals of the Rheumatic Diseases, dives into the mechanisms behind the female bias in autoimmune diseases, specifically SLE. Historically, it has been believed that skewed XCI—where one X chromosome is preferentially inactivated—might be a contributing factor to the higher prevalence of lupus in women. However, our study suggests that rather than being a cause, reduced XCI skewing may be a consequence of the disease itself.
Using a large cohort of women with lupus, alongside a twin study, Dr. Roberts and her team found that lupus patients, particularly those with more severe forms of the disease, showed less skewed X chromosome inactivation compared to healthy participants. This finding was not only statistically powerful but also calls into question existing theories about how XCI contributes to the development of lupus.
This recognition from Nature Reviews Rheumatology signifies the importance and impact of this work. By pushing the boundaries of what we know about lupus and X chromosome inactivation, this research opens new questions and avenues for future exploration into autoimmune diseases. We are incredibly proud of Dr. Roberts and her team for their continued dedication to advancing our understanding of these complex conditions.
Congratulations to everyone involved in this exciting achievement! You can read the full review in Nature Reviews Rheumatologyhere.
A recent study has explored how our genes influence the way our skin’s DNA is chemically marked – a process known as DNA methylation. This discovery could help us better understand various skin conditions and how we age.
DNA methylation involves adding chemical tags to our DNA that can turn genes on or off. It’s known that these chemical tags can be affected by both our environment and our genes. Previous research mainly focused on blood samples, showing that a significant portion of DNA markers in our blood is due to our genetic makeup.
However, skin plays a crucial role in protecting us from harm and regulating our body. Changes in skin DNA methylation have been linked to issues like melanoma (a type of skin cancer), the number of moles, and signs of aging. While past studies have looked at these changes in specific skin cells and cancer cells, there hasn’t been a comprehensive study of the entire skin’s DNA.
The latest research, using data from TwinsUK, has filled this gap. Scientists studied the DNA and gene activity of 414 female twins to understand how genetic factors influence skin DNA methylation. They found that the influence of genes on skin DNA is less than in other tissues, with an average genetic contribution of 10.02%.
The researchers found thousands of genetic variations that affect how DNA methylation occurs in the skin. These variations also influence gene activity, which could have implications for understanding skin health and diseases. For instance, they identified specific genetic markers linked to conditions like melanoma and psoriasis, as well as markers associated with ageing.
These findings reveal that our genes play a significant role in how our skin responds to various factors, including aging and disease. This research not only enhances our understanding of skin health but also opens up possibilities for new treatments based on these genetic insights.
For more details, you can read the full article here.
Researchers at TwinsUK have conducted a study examining the role of the X chromosome in systemic lupus erythematosus (lupus), an autoimmune disease that predominantly affects females. The study, involving nearly 1,000 female participants, found significant differences in X Chromosome Inactivation (XCI) between lupus patients and healthy controls.
Lupus is a condition where the immune system attacks the body’s tissues, leading to inflammation and damage. Despite extensive research, the reasons why 90% of lupus patients are female remain unclear. One theory suggests that the sex chromosomes, particularly the X chromosome, may play a role.
In females, one of the two X chromosomes is randomly inactivated in each cell, a process known as XCI. This study measured changes in XCI in immune cells and discovered that only 7% of lupus patients showed changes in XCI, compared to 30% typically seen in healthy females. Moreover, among those with more severe lupus, only 3% exhibited changes in XCI.
To further validate these findings, researchers studied twin pairs from TwinsUK where one twin had lupus, and the other did not. The results were consistent: twins with lupus had fewer changes in XCI than their healthy counterparts.
Interestingly, these findings differ from previous research on other autoimmune diseases such as thyroid disease and rheumatoid arthritis, indicating distinct mechanisms underlying different autoimmune conditions. Instead of a broad pattern of XCI changes, the study found a correlation between XCI and the “interferon signature,” a marker of lupus disease activity.
These insights suggest that the role of XCI in lupus is unique and may not follow the patterns observed in other autoimmune diseases. More research is needed to understand how these changes in XCI affect immune function and their implications for infection defence, especially as individuals age.
First author Dr. Amy Roberts explained:
“Thanks to the TwinsUK volunteers, we were able to demonstrate differences in X chromosome inactivation between healthy controls and people with lupus. Not only does this research help us understand lupus but also how our immune system changes with age – an area we are actively researching further.”
This study represents a significant step forward in understanding the complex biology of lupus and underscores the importance of examining sex-specific factors in autoimmune diseases.
As a BSc Biomedical Science student at Imperial College London, I had not been lucky enough to interact directly with many participants of research studies. On only the second day of my internship with TwinsUK I was able to watch a pair of twins throughout their visit to the study clinic. The twins were extremely friendly and a pleasure to talk to, but I was most surprised at how happy they were to take part in the study. I do not know many twins personally, so it was heartwarming to sense the connection between two people who seem to be so in tune with each other. The particular set of twins that I shadowed live in different parts of the country and so aside from taking part in the study, the clinic visit was a nice opportunity for the twins to catch up with each other.
My typical experience of science has been studying samples at the lab bench or analysing results on the computer. It felt refreshing to observe the twins on their visit to begin to establish an idea of how the data I so often work with is actually produced. I believe that experiences such as this, where researchers are confronted with the faces behind the data they receive, are extremely important for producing well-rounded scientists who can appreciate the massive contribution of study participants to their work.
It was also interesting to see certain ideas from throughout my studies in practice. For example, research ethics (that is, how to carry out research in a way that is moral) was something I had learned during university. During my time at TwinsUK, I was shown the high standards that the researchers hold themselves to. To me, it is more important than ever to ensure that ethical standards are maintained as more people participate in scientific research than ever before.
This experience was extremely eye-opening for me as I was able to witness firsthand the sheer amount of effort that goes into coordinating a massive research department like TwinsUK. I have seen that the success of TwinsUK is, in part, due to the huge sense of collaboration that encompasses the group. Every person I interacted with during my first week welcomed me and tried their best to ensure my comfort. Alongside this, everyone was very open and willing to spend a few minutes chatting with me about their individual role within the wider research group.
As I come to the end of the first week of my internship with TwinsUK, I feel reassured about entering the world of research in the near future. I have seen the variety of roles available to me as a young scientist and have gained a deeper appreciation for the huge contribution that participants make to the progress of scientific research. I am immensely grateful for this opportunity and am looking forward to the rest of my summer with the TwinsUK team.