Halloween at TwinsUK

28th October 2021 – By Emily Stevens

bats, trees and big glistening moon in the background

Night falls across the creeping Thames, glass glitters under the clouded sky, a sliver of the moon breaks through, and stirring autumnal wind crosses the glimmering edifice of St Thomas’ Hospital. Approaching winter seems to hang in the air as shadows lengthen in the evening light. These shadows climb the walls of the hospital.

Some windows are lit, some are not. If ghosts walk the halls, Agnes Elizabeth Jones nods to Florence Nightingale, and William Cheselden wonders how much mercury Isaac Newton ingested.

In the Twin Research clinic, samples of all kinds have been collected. This includes around 300,000 aliquots of blood, stored as serum and plasma. From finger-prick bloods to phlebotomy blood draws, a prowling vampire would be fascinated. Blood and guts are the source from which discoveries spring.

Through corridors, through laboratories under fluorescent light, the penumbral night seeps. Every catalogue of Halloween costumes tends to include nurse’s scrubs – hospitals can be spooky, can be cinematic. So can twins—the unheimlich, or the uncanny, plays on the material of life. I’m reminded of Michael in Caryl Churchill’s play ‘A Number’ pointing out: ‘We’ve got thirty percent the same [DNA] as a lettuce. Does that cheer you up at all? What I love about the lettuce. It makes me feel I belong.’

The trees along the river quiver down below. Curtains flutter in the breeze, woodsmoke drifts from distant bonfires. Beyond the clinic windows, clouds swirl in the sky like a witch’s cauldron.

From the clinic and labs of TwinsUK: Happy Halloween!

Hungry all the time? Now we know why

21st April 2021

People who experience big dips in blood sugar levels several hours after eating end up feeling hungrier and consuming hundreds more calories during the day than others, according to the latest findings from the PREDICT study.

The results, published in Nature Metabolism, explain why some people struggle to lose weight, even on calorie-controlled diets, and highlight the importance of understanding personal metabolism when it comes to diet and health.

Dr Sarah Berry from King’s College London said:

“It has long been suspected that blood sugar levels play an important role in controlling hunger, but the results from previous studies have been inconclusive. We’ve now shown that sugar dips are a better predictor of hunger and subsequent calorie intake than the initial blood sugar peak response after eating, changing how we think about the relationship between blood sugar levels and the food we eat.”

The research

PREDICT is the largest ongoing nutritional research programme in the world that looks at responses to food in real life settings.

The research team collected detailed data about blood sugar responses and other markers of health from 1,070 people after eating standardised breakfasts and freely chosen meals over a two-week period, adding up to more than 8,000 breakfasts and 70,000 meals in total.

Participants wore stick-on continuous glucose monitors (CGMs) to measure their blood sugar levels over the entire duration of the study. They also recorded levels of hunger and alertness using a phone app, along with exactly when and what they ate over the day.

Previous studies looking at blood sugar after eating have focused on the way that levels rise and fall in the first two hours after a meal, known as a blood sugar peak. After analysing the data however, the PREDICT team noticed that some people experienced significant ‘sugar dips’ 2-4 hours after this initial peak, where their blood sugar levels fell rapidly below baseline before coming back up.

Big dippers had a 9% increase in hunger, and waited around half an hour less, on average, before their next meal than little dippers, even though they ate exactly the same meals.

Big dippers also ate 75 more calories in the 3-4 hours after breakfast and around 312 calories more over the whole day than little dippers. This kind of pattern could potentially turn into 20 pounds of weight gain over a year.

Professor Ana Valdes from the School of Medicine at the University of Nottingham, who led the study team, said:

“Many people struggle to lose weight and keep it off, and just a few hundred extra calories every day can add up to several pounds of weight gain over a year. Our discovery that the size of sugar dips after eating has such a big impact on hunger and appetite has great potential for helping people understand and control their weight and long-term health.”

Everyone is different

Comparing what happens when participants eat the same test meals revealed large variations in blood sugar responses between people. The researchers also found no correlation between age, bodyweight or BMI and being a big or little dipper, although males had slightly larger dips than females on average.

There was also some variability in the size of the dips experienced by each person in response to eating the same meals on different days, suggesting that whether you’re a dipper or not depends on individual differences in metabolism, as well as the day-to-day effects of meal choices and activity levels.

Tim Spector, Professor of Genetic Epidemiology at King’s College London and scientific co-founder of ZOE, concluded:

“Food is complex and humans are complicated, but our research is finally starting to open up the black box between diet and health. We’re excited to have been able to turn this cutting-edge science into an at-home nutrition and microbiome test so that everyone has the opportunity to discover their unique responses to food to best support their metabolism and gut health.”

TwinsUK to take part in key Long COVID research programme

22nd February 2021

TwinsUK will be joining forces with other cohort studies across the UK to study Long COVID through a key project announced last week.

Approximately one in 10 people with COVID-19 continue to experience symptoms and impaired quality of life beyond 12 weeks, known as Long COVID.

The project, which has received £9.6 million in funding from UKRI over three years, aims to provide an evidence base for healthcare services to define what Long COVID is and improve diagnosis. The project will address why some people get the condition; the typical effects on a person’s health and ability to work; and the factors which affect recovery.

Dr Claire Steves, Deputy Clinical Director of TwinsUK, will be leading TwinsUK’s contribution to the project. Dr Steves said:

“I am thrilled that TwinsUK will be involved in this national effort to study Long COVID and its long-term effects. This research is essential so that we can understand how healthcare services can best support people experiencing Long COVID.”

Long COVID can present with clusters of symptoms that are often overlapping and/or fluctuating. Symptoms vary, but common ones include breathlessness, headaches, cough, fatigue, cognitive impairment or ‘brain fog’. Long COVID may comprise several distinct syndromes not yet fully understood and these studies will help solve this.

Over the three years of the project, the team of researchers will use data from more than 60,000 people drawn from a combination of anonymised health records and longitudinal studies of people of all ages across the country (like TwinsUK).

From these studies, people reporting Long COVID and comparator groups will be asked to wear a wrist band measuring exercise ability, breathing and heart rate. Participants will also complete online questionnaires on mental health and cognitive function. They may also be invited to a clinic for non-invasive imaging to look at potential damage to vital organs, such as the brain, lungs and heart.

Dr Claire Steves said:

“Throughout the pandemic, our twins have taken part in a variety of essential studies to understand COVID-19. I am grateful for and humbled by their commitment to health research, a feeling which I know is shared by everyone at TwinsUK.”

A good diet can keep us healthy – but are we really in control of what we eat?

18th January 2021 – by Paz García

Your food intake patterns are partly under genetic control, according to the latest research from TwinsUK.

First author Olatz Mompeó-Masachs explained:

“We know from previous twin studies that there is a strong genetic component for specific foods such as coffee and garlic, as well as overall eating habits. Our latest study is the first to show that food and nutrient intake, as measured by nine dietary indices, is also partly under genetic control.”

Researchers can study the quality of an individual’s typical diet by using a type of analysis called ‘dietary indices’. Researchers use dietary indices to understand what foods someone eats and the nutrients provided, compared with recommended guidelines.

The team analysed food questionnaire responses from 2,590 TwinsUK members, using nine commonly used dietary indices.  The researchers studied the degree of similarity among identical twins – who share 100% of their genes – compared with non-identical twins, who share 50% of their genes.

The team found that identical twin pairs were more likely to have similar scores across nine dietary indices compared with non-identical twin pairs. This was the case even when other factors were taken into account, such as body mass index (BMI) and exercise levels. The results indicate that there is a genetic component to food intake patterns.

Senior author Dr Massimo Mangino said:

“Our study represents the first comprehensive investigation of the contributions of genetic and environmental factors to the variation in eating behaviour. It highlights the complex relationship between genetic and environment and may have future implications for public health nutrition campaigns.

“This study used food data from female twins only, with an average age of 58. Future research will need to look at dietary indices across a more varied group of people to see if the same findings hold true.”

What’s in a colon? New project ExHiBITT publishes first results

13th February 2020 – Paz Garcia

Even healthy people have abnormalities in their colon, according to the first results of new study ExHiBITT published today.

Researchers found that 28% of participants had polyps in the colon, which are small tumours on the surface of the colon lining that are typically detected in about a third of all colonoscopies. Researchers and doctors are interested in colonic polyps as in some cases they can lead to bowel cancer.

The colon is the last part of the digestive system and is a key location where microbes process any remaining solid waste before it is passed out as stool.

The aim of ExHiBITT – which stands for Exploring Host microBIome inTeractions in Twins – is to understand how our bodies interact with the billions of microbes in our colons.

The study was led by the Department of Twin Research in collaboration with researchers from Experimental Immunobiology from King’s College London and Guy’s and St Thomas’ Hospitals NHS Foundation Trust.

What did they find?

Over 200 healthy identical twins from TwinsUK took part in the study. The participants completed health questionnaires and provided samples including saliva, blood, stool and four colon biopsies obtained through a colonoscopy.

The researchers found that 28% of participants had polyps in their colon and 26% had previously undiagnosed diverticulosis, which is where small pockets form in the colon wall. People who have diverticulosis often do not feel any symptoms and the condition does not lead to cancer.

Participants with higher age and weight for their height (BMI) had a greater number of polyps, and if one twin in a pair had polyps, the chance of the other twin having polyps was 42%.

What’s next?

The team are now planning to study in closer detail the microbes identified in the samples to understand how it may influence our health. This includes analysing each participant’s metabolism and that of their microbes, as well as sequencing the microbes’ DNA. The researchers will use this information to create a rich database that will be available for other researchers to use, so that more health research can take place using the data generated by ExHiBITT.

Lead researcher Dr Marina Mora-Ortiz said:

“These findings are just the beginning and we’re now getting started on the next stage of analysing the collected samples. We’d like to say a huge thank you to our twins for taking part in this study, especially considering it involved a colonoscopy! We are always humbled by the contribution our selfless volunteers are willing to make to support medical research.”

Introducting ExHiBITT – Exploring Host microBIome inTeractions in Twins -, a colon multiomic cohort study (2020) Mora-Ortiz et al., Wellcome Open Research.

Chromosome X marks the spot

25th November 2019 – by Paz Garcia

The X chromosome in women shows up differently in different parts of the body, according to new research published today in Nature Communications.

This means that women may not benefit from technologies that predict health risks based on genes on the X chromosome.

The team, led by researchers from the Department of Twin Research & Genetic Epidemiology, also found that age affects the patterns of X chromosomes, through a process known as “X inactivation”.

Further research is needed to understand the impact of different patterns of X inactivation on healthy ageing in women and how it can be taken into account when developing genetic tools that predict health risks.

What is X inactivation?

Chromosomes are lengths of DNA that contain genes on them.

Males have both an X and a Y chromosome, and females have two X chromosomes (XX). Humans only need one dose of the genes on the X chromosome however, so in females one of the X chromosomes in every cell is “switched off” so they don’t get double the dose. This process is known as X inactivation.

Which of the two X chromosomes is switched off is random, leading to roughly equal levels of each in the body.

Evidence suggests however that in some body parts in women, one X chromosome is much more likely to be inactivated than the other, leading to skewed patterns of X inactivation across different body parts.

What did they do?

The team, led by Dr Kerrin Small and Antonino Zito, studied whether the skew of X chromosome inactivation is linked to genetics, age, smoking and autoimmune diseases.

The researchers studied blood, fat and skin samples from almost 800 twins, including 8 pairs where one twin had rheumatoid arthritis – an autoimmune condition – and the other twin did not.

What did they find?

Blood, fat and skin have different X chromosome inactivation patterns. These patterns become more skewed with age and smoking. In addition, genetics affect the skewed patterns in the blood, but not in fat or skin.

The team also found that twins who have autoimmune conditions have more skewed patterns of X chromosome inactivation in the blood than their co-twins without the condition.

What does this mean?

Researchers will need to take into account the differences in X inactivation throughout the body in females.

First author Antonino Zito explained:

“It’s important to note that X inactivation patterns in the blood are not a reliable indicator of X inactivation in other parts of the body. We need to take this into account when designing genetic tools to predict health risks, which often rely on specialised blood tests. Otherwise, it may be that future genetic health tests are less reliable for older women, as the dose of X chromosome genes in the blood sample is different to that found elsewhere in the body.”

Senior author Dr Kerrin Small added:

“Our results indicate an association between X inactivation patterns and genetics, age, smoking and autoimmune conditions. We will need to carry out further research to understand the relationship between these features, and the implications of skewed X inactivation for healthy ageing in women.”

Zito A, Davies MN, Tsai PC, Roberts S, Andres-Ejarque R, Nardone S, Bell JT, Wong CCY and Small KS. Heritability of skewed X-inactivation in female twins is tissue-specific and dependent on age. Nature Communications (2019)

Gut bacteria need each other – and that affects our metabolism

3rd October 2019 – by Paz Garcia

Pile of lego bricks
Gut bacteria work together like Lego

Teamwork is key for the trillions of bacteria that live in our gut and this has a big impact on our metabolism, according to new research led by King’s College London, published today in Nature Communications.

The human gut is home to bacteria that help us digest our food, produce vitamins and perform many other tasks that influence our health.

Gut bacteria work together in groups to carry out different functions. The researchers, led by the Department of Twin Research & Genetic Epidemiology, found that this teamwork is much more important and more closely linked with our metabolism than individual species of bacteria.

The researchers studied the gut bacteria, blood and stool of over a thousand twins who take part in TwinsUK. This allowed the team to run the first large study on the link between gut bacterial species, their functions and the metabolism in the gut and blood of the participants.

The team found that while unrelated people share only 43% of gut bacteria species, they still share 82% of functions carried out by groups of gut bacteria. This is because different bacterial species can contribute to the same function and so different groups can work together to can carry out similar activities.

This research therefore suggests that health treatments designed to target gut bacteria – and our metabolism – should focus on groups of gut bacteria that carry out a particular function, rather than individual bacterial species.

Senior author Dr Mario Falchi explained:

“We can think of our gut bacteria like Lego bricks – the colour of the bricks doesn’t matter as much compared with how they fit together to make something. With gut bacteria, the individual species don’t matter as much as the group working together to carry out a function.”

“This is the first large study to explore the metabolic potential of the entire gut bacteria ecosystem. Our findings underline the importance of studying groups of bacteria and their functions overall, rather than focusing on specific species. These results add to the growing body of evidence that gut bacteria are intrinsically linked with human health.”

*

Visconti A, Le Roy CI, Rosa F, Rossi N, Martin TC, Mohney RP, Li W, de Rinaldis E, Bell JT, Venter JC, Nelson KE, Spector TD and Falchi M. Interplay between the human gut microbiome and host metabolism. Nature Communications (2019).

Hope for hearing loss

26th September 2019 – by Paz Garcia

Hand holding a hearing aid against a green background

A new study of over 250,000 volunteers has identified 44 new genes linked to age-related hearing loss.

A third of people are affected by some degree of hearing loss by the age of 65, which can lead to social isolation and disability.

Despite being such a common sensory impairment, hearing aids are the only treatment available and not much is known about the genes behind the condition.

These findings will help researchers understand how hearing loss develops and so help us find ways to treat and prevent the condition.

Professor Frances Williams, who led the collaborative research using data from UK Biobank, TwinsUK and ELSA among others, explained: 

“We now know that very many genes are involved in the loss of hearing ability as we age. This study has identified genes that we know already cause deafness in children, but it has also revealed lots of additional genes which point to new biological pathways.”

The study is the largest genetic analysis conducted to date of people who report problems with their hearing.

The work was from a joint project involving King’s College London and University College London.

What did they do?

The team wanted to identify the genetic component of adult hearing loss in the UK so that we can understand better how the condition develops as we age.

The researchers analysed the genetic data and questionnaire responses about hearing in over 250,000 participants of the UK Biobank aged 40-69 years to see which genes were associated with people who had self-reported hearing problems.

The team identified 44 new genes linked with age-related hearing loss of which 34 have not been linked to any form of hearing loss previously.

The researchers then checked their findings by studying TwinsUK and the English Longitudinal Study of Ageing.

What does this mean?

These finding will help researchers untangle the sequence of events that lead to hearing impairment as we age. Future research will investigate the biological hearing pathways influenced by these genes.

This will help us to identify possible targets for new therapies to treat and potentially prevent or delay hearing loss with age.

Wells et al., GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank, The American Journal of Human Genetics (2019).

27 years of seeing double

17th September 2019 – by Paz Garcia

Every four years since 2000, identical twins Tracey and Julia make a trip to St Thomas’ Hospital in London. But they don’t go for treatment – they go to meet researchers who are working to make new treatments possible for others.

Tracey and Julia are two out of more than 14,000 twins who take part in TwinsUK, a study which follows twins throughout adulthood to understand how various health conditions develop and the genetics behind them.

They signed up to TwinsUK after a former colleague mentioned it to them, as Julia explained:

“My sister Tracey convinced me to sign up to TwinsUK. One of Tracey’s work colleagues mentioned the study to her as she’d signed up with her twin. After reading an article in Woman’s Own magazine, we both joined TwinsUK 6 months after the initial launch.”

Julia and Tracey

Studying twins

How can we tell whether a particular condition is due to genetics and/or our environment and lifestyle? The answer of course is twins.

Professor Tim Spector is the Director of TwinsUK. What started as an arthritis study with a few hundred twins in 1992 turned into what we now know as TwinsUK – a long-term study of 14,000 twins.

Professor Spector explained the reasoning behind studying twins:

“Twins are the perfect experiment. Identical twins have identical genes. Non-identical twins, or “fraternal” twins, only share half their genes with each other. We can make comparisons to work out to what extent nature or nurture cause different conditions and diseases.”

When both twins in a pair have the same condition, researchers say they are ‘concordant’. If only one twin in a pair has the condition and the other doesn’t, they are ‘discordant’. Researchers can then design studies which take advantage of twins’ unique set-up.

For example, if more identical twin pairs are concordant for a particular condition than non-identical twins, then that condition is likely influenced to a greater extent by genes than by the environment.

Conversely, if identical twin pairs are discordant for a particular condition, then researchers can investigate whether other aspects such as their environment or lifestyle may have a stronger influence on the development of the condition.

That’s not all twins can do. TwinsUK is uniquely placed to identify the molecular systems underpinning health and development of disease. The sheer volume of data TwinsUK collects means that their twins are amongst the most studied in the world. TwinsUK holds hundreds of thousands of pieces of information. Genetics, age, weight, blood pressure, bone density, gut bacteria, blood cell counts – you name it, they have it. As if that wasn’t enough, TwinsUK now wants to ramp up data collection and explore personal, social and ambient environmental influences in more detail. This includes studying the impact of things such as physical lifestyle, pollution, pesticides and inequality.

The researchers are not trying to answer one big question with all this data. They’re working in a wide range of areas such as ageing, type 2 diabetes, back pain and sensory impairment, to answer lots of different questions about health and how conditions develop throughout the life course of an adult. All of the work brings us closer to understanding how the human body works – in sickness and in health.

Sharing is caring

TwinsUK doesn’t carry out their work alone. Considering the enormous amount of data collected, it wouldn’t be possible, and there are lots of other researchers and specialists who want to take a closer look at the data as part of their own research.

Dr Claire Steves, Deputy Clinical Director for TwinsUK explained:

“It’s important that we share our data with other health researchers so that we can make the best use of it. It’s only fair to the twins – after all, it would be unethical not to get the most value out of the samples and health measures they so generously provide.”

To this end, the TwinsUK Resource Executive Committee has approved more than 800 data sharing requests, covering 150,000 samples shared with 100 collaborators. This means that even years after it was collected, the twins’ data and samples continue to be used to advance health research for everyone.

That’s not where the sharing ends either. TwinsUK has contributed to more than 850 scientific publications as well, ensuring that the results of health research carried out using the twins’ data and samples are made available to other researchers around the world.

Looking ahead, TwinsUK has ambitions to work more closely with other cohort studies, particularly other twin studies. This will encourage more cross-cohort work, and researchers will be able to learn from each other – which can only be a good thing for health research.

The twin experience

Sharing data and publishing the results of research however are the end products of a research process that starts with the twins. Central to TwinsUK are the twin visits, where pairs of twins come into St Thomas’ Hospital for a full day of mental and physical health checks and tests. In addition, twins may be offered the chance to take part in specific studies that TwinsUK is carrying out at that time.

“The visits up to St Thomas’ have been interesting and revealing. It’s great that you have the opportunity to help with research, from taking vitamin supplements, which helped with research into eye problems, to having MRI scans to check the brain,” mused Tracey.

Some of the tests may be unusual, but that doesn’t deter Julia:

“The studies and tests are also very safe. The fact that any procedures and studies are carefully and intricately explained makes me feel relaxed about what’s going to happen. It’s always interesting and sometimes fascinating or even surprising to hear the results of the studies.”

Tracey added:

“Finding out we were tone-deaf was surprising, but answered a few questions as to why music always sounded perfect!”

The twins do receive some health test results, but most take part to help with research, like Julia:

“Personally, I feel honoured to be a part of TwinsUK and if the studies my twin and I take part in can help make a difference to other people’s health then that has got to be a good thing.”

Looking ahead

The TwinsUK team has no intention of slowing down. TwinsUK wants to remain at the cutting edge of scientific cohort studies, and so the team are looking to expand: their connections, their data collection, and most importantly, their registry.

Whereas up until now TwinsUK has only studied adults, they recently received permission to recruit and study twins all the way from birth. This adds another dimension to the research programme, and will help researchers understand how diseases develop throughout the whole life course of a person.

Dr Deborah Hart, Executive Director:

“We’re really excited to be opening up TwinsUK to more people. Like Tracey’s work colleague, if you’re a twin and know some twins who would be interested, do point them towards us.”

And for anyone thinking about signing up, Tracey has a few words of encouragement:

“The staff and twins that you meet have been amazing. I can honestly say it’s been lovely taking in part with the research, and I’ve made lovely friends and memories along the way.”

TwinsUK is currently recruiting same-sex identical and non-identical twins over the age of 18. We will soon begin to recruit under 18s. Find out more on twinsuk.ac.uk/twinzone or call the team on 020 7188 5555.

Read the paper here – TwinsUK: The UK Adult Twin Registry Update

TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.

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