New research has demonstrated the heritability of anti-viral antibody selection among a cohort of identical twins.
The study, published today in Cell Press and led by researchers from King’s College London in collaboration with the John Hopkins University, investigated for the first time whether epitope selection – the part of the antigen molecule which an antibody attaches itself – is heritable.
There is a high degree of variability in human immune responses to viral infections. The genetic factors that influence this variability are not well explored. TwinsUK is the UK’s largest adult twin registry consisting of identical twins. Identical (monozygotic) twins come from a single fertilised egg that splits in two and share most of their genetic material. As such, most of their differences (either physical or behavioural) are likely to be the results of environmental factors.
Researchers from TwinsUK compared samples from identical twins with fraternal twins to measure the heritability of the antibody repertoire and identify genetic loci driving antibody responses in humans.
They used VirScan, a virome-wide antibody profiling technology, to measure the heritability of epitope selection.
The results found epitope selection is a heritable trait. They also utilised genome-wide association analysis to identify genetic loci linked to Epstein-Barr Virus (EBV) antibody epitope selection and identified a key role for HLA-DR (MHC-II) in selecting certain dominant EBV epitopes.
First author Dr. Massimo Mangino from King’s College London said:
“Our study represents the first comprehensive investigation of the contributions of genetic and environmental factors to the variation in the antibody responses to viral infections. It highlights the complex relationship between genetic and environment and may provide a novel framework for identifying genes important for pathogen immunity.”
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
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.
up to TwinsUK after a former colleague mentioned it to them, as Julia
“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.”
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.
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.”
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.
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.
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.
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
Sharing is caring
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
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.
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.
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
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.”
“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,
“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.”
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.
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.
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.”
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.
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.