General – TwinsUK

TwinsUK Launches New Fat Biopsy Study with First Twin Pair

Posted on 13/02/202513/02/2025 by Aaruthy Suthahar

Thursday 13th February – by Aaruthy Suthahar

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.”

Low levels of mercury exposure impact molecular processes

Posted on 05/02/202513/02/2025 by Aaruthy Suthahar

5th February 2025 – by King’s College London

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.

Read the full paper here.

TwinsUK Study Shortlisted for Versus Arthritis Research Highlight of the Year

Posted on 13/01/202503/02/2025 by Aaruthy Suthahar

13th January 2025 – by TwinsUK

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.

Unlocking the secrets of our fat: New study uncovers how genetics acts through fat tissue to shape health and disease

Posted on 09/01/202503/02/2025 by Aaruthy Suthahar

9th January 2025 – by Aaruthy Suthahar

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.

Our Research on X Chromosome Inactivation in Lupus Receives Featured Review in Nature Reviews Rheumatology

Posted on 03/10/202403/10/2024 by Aaruthy Suthahar

1st October 2024 – by Aaruthy Suthahar

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 Rheumatology here.

New Insights into How Our Genes Affect Skin Health

Posted on 26/09/202426/09/2024 by Aaruthy Suthahar

Thursday 26th September – by Aaruthy Suthahar

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.

Study Sheds Light on the Role of X Chromosome Inactivation in Lupus

Posted on 31/07/202401/08/2024 by Aaruthy Suthahar

31st July 2024 – by Aaruthy Suthahar

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.

Largest Ever Genetic Study of Age of Puberty Includes TwinsUK Contribution

Posted on 17/07/202417/07/2024 by Aaruthy Suthahar

17th July 2024 – by Aaruthy Suthahar

In a study published in Nature Genetics, researchers conducted the largest-ever investigation into the genetic determinants of pubertal timing in girls, analysing data from approximately 800,000 women worldwide. This study has identified 1,080 genetic signals associated with the age at menarche (the first menstrual cycle in females), significantly advancing our understanding of the genetic influences on puberty and its links to later health outcomes.

TwinsUK, which provided data from around 6,000 twin participants, played a great role in this large-scale study. The inclusion of twins’ genetic information allowed researchers to delve deeper into the hereditary patterns and environmental interactions that influence pubertal timing.

The study found that women with very high or very low genetic risk had much higher chances of experiencing puberty either very late or very early. Specifically, women in the top 1% of genetic risk were 11 times more likely to have delayed puberty, while those in the bottom 1% were 14 times more likely to have early puberty. Researchers also found that some rare genetic changes, especially in the ZNF483 gene, could cancel out the effect of overall genetic risk.

The study also discovered 665 genes linked to when puberty starts, including the GPR83 gene, which helps the body detect changes in nutrition and send hormonal signals. The results suggest a link between the timing of puberty and menopause, pointing to a shared mechanism in the ovaries that might influence both stages of life.

The study has garnered significant media attention, with detailed coverage provided by the University of Cambridge. For more information, you can read the Cambridge press release HERE.

TwinsUK participants can take pride in knowing that their contributions are helping to advance scientific knowledge in critical areas of health and development. The findings from this study not only enhance our understanding of puberty but also open up potential avenues for addressing related health issues in the future.

For further details on the study, you can access the full article in Nature Genetics HERE.

Researchers challenge focus on rural older adults in Chris Whitty’s latest health report

Posted on 04/06/202406/06/2024 by Aaruthy Suthahar

Tuesday 4th June – by Aaruthy Suthahar

In a report published this week in Clinical Medicine, researchers from the Centre for Ageing Resilience in a Changing Environment (CARICE) show that contrary to that suggested in Chris Whitty’s latest annual Chief Medical Officer (CMO) report for England, most older adults live in urban areas rather than rural areas. Adding in self-reported health as a measure of need for services, a more complex picture of ageing demographics emerged, suggesting a need for a nuanced understanding when planning healthcare services and resource allocation.

According to Nathan Cheetham, Senior Postdoctoral Data Scientist:

“Chris Whitty’s latest report as Chief Medical Officer highlights the importance of understanding the geography of ageing in England. However, it’s crucial to consider both absolute and relative population metrics for a comprehensive view.”

Census 2021 data indicates that approximately three-quarters of older adults in England and Wales, equivalent to 8.4 million individuals, live in urban regions. This challenges the emphasis placed on rural and coastal areas in the CMO report.

Professor Claire J. Steves, specialising in Ageing and Health, emphasises:

“We need to move beyond simplistic rural-urban dichotomies when planning healthcare services. The absolute numbers and health needs of older adults in urban areas demand attention. This is particularly important as we experience more climate change-related heat waves which mostly affect urban hotspots. Older people living in such places also tend to be more vulnerable.”

“This is particularly important as we experience more climate change-related heat waves which mostly affect urban hotspots. Older people living in such places are the most vulnerable group.”

Projected population growth further complicates assumptions about urban-rural dynamics. Rather than shrinking, urban areas are projected to experience significant growth in older populations over the next two decades, with a projected increase of 43% compared to 48% in rural areas by 2043.

Disparities in health outcomes underscore the need for subtle policy responses, urban-dwelling older adults are not only more numerous but also more likely to reside in deprived neighbourhoods and report poorer health compared to their rural counterparts.

Investing in preventive measures and understanding the diverse needs of older adults across different geographical areas is imperative for ensuring equitable healthcare provision.

As policymakers navigate the evolving landscape of ageing demographics, a comprehensive approach considering both absolute numbers and health indicators is vital for effectively addressing the healthcare needs of older adults in England.

Study Reveals ZOE Personalised Diets Yield Health Improvements

Posted on 09/05/202409/05/2024 by Aaruthy Suthahar

9th May 2024 – by Aaruthy Suthahar

In a recent study published in the scientific journal Nature Medicine, researchers from ZOE, who are running the largest in-depth nutrition study in the world, examined the impact of personalised dietary advice versus general recommendations on cardiometabolic health. This study, involving 347 participants aged 41 to 70 years, sheds light on the effectiveness of tailored dietary programmes.

Participants were randomly assigned to either receive personalised dietary guidance by ZOE or standard care advice based on the US Department of Agriculture Guidelines for Americans. The personalised dietary programme utilised various factors including food characteristics, individual responses to food, microbiomes, and health history to create personalised food scores over an 18-week period.

Results showed a significant reduction in triglyceride levels, which are types of fat in the blood, among participants following the personalised dietary programme compared to those receiving standard advice. However, there were no significant changes in low-density lipoprotein cholesterol. Additionally, improvements were noted in other measures such as body weight, waist circumference, HbA1c levels (which is a measure of blood sugar over time), diet quality, and the variety of gut bacteria, particularly among participants who closely followed the personalised programme.

It is noteworthy that participants following the ZOE programme reported feeling better, with improvements in mood, reduced hunger, better sleep, and increased energy compared to the control group. Those who closely adhered to the ZOE advice also experienced greater improvements in weight and increases in diet quality, associated with lower risk for heart disease and diabetes.

Overall, the study shows the potential benefits of personalised dietary advice in improving cardiometabolic health outcomes, providing valuable insights for individuals seeking effective dietary interventions. TwinsUK members were instrumental in enabling ZOE to develop their personalised dietary programme through the original research study on personalised diets, PREDICT.

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