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Seeing doubles

18 Dec, 2008

Every year, researchers at the Department of Twin Research, King’s College London, play host to around 1000 twin visits. Chrissie Giles went along with her identical twin, Katie, to see what it’s like to be at the sharp end of a scientific study.

I’m sat in a narrow consulting room, gripping as hard as I can on a strange piece of equipment I’m told is called a hand dynamometer. Across the desk, my twin sister, Katie, is doing the same, her face screwed up in determination to grip harder than me. The research nurse tells us that, according to the chart on the wall, we’re both distinctly average at gripping.

The dynamometer was just the start. By the end of our half-day visit to the Department of Twin Research, based at St Thomas’ Hospital in London, we’d undergone a barrage of tests. We’d been weighed and measured, bled, had our inner arms exposed to the chemical responsible for burning in chillies, and been asked to judge which of a selection of well-known melodies had out-of-tune notes included.

Audio: extract from an interview with Prof. Tim Spector, Director of the Department of Twin Research [03.27].

My sister and I volunteered to be part of TwinsUK several years ago. The only adult twin registry in the UK, TwinsUK contains clinical, demographic and lifestyle data from around 11 000 mostly female identical and non-identical twin pairs aged between 16 and 100, who have been randomly sampled from the UK population. Much of the information is collected during visits to the Department, and this was our first trip there.

Typically, visitors undergo a number of checks, including height, weight, blood pressure and lung function tests, ECG, bone mineral density scans, eye tests, facial photographs and cognitive tests. They are also fitted with a monitor to measure physical activity and heart activity over a week, and some have biopsies taken from muscle, fat and skin, or moles.

My sister has an ECG while I remove anything metallic from my person and climb on to the DXA (dual energy X-ray absorptiometry) bone scanner. I have to lie still for almost 10 minutes as the machine moves up and down my body, and the table I’m lying on glides silently from side to side. Then we swap places.

During the visit we also complete a series of questionnaires, which are similar to those sent every year to the twins on the register. These questionnaires often cover an intriguing mix of subjects: everything from obsessive-compulsive behaviour, through religious beliefs, to personal experience of baldness.

As the researchers stick identification stickers on the blood tubes and paperwork, they explain that the information and samples are being collected as part of the Healthy Ageing Twin Study. Funded by the Wellcome Trust, this study is designed to explore the genetic aspects of common diseases of ageing such as osteoporosis, osteoarthritis and obesity, as well as those affecting the cardiovascular system and the eye.

It is one of over 20 different funded projects underway within the Department of Twin Research, which is staffed by over 40 researchers (including nurses, statisticians and laboratory personnel) – a marked change from the Department’s modest beginnings in 1992.

“From a small grant with two staff we originally looked at whether osteoporosis is genetic or not, since then our study has expanded slowly and steadily,” says Tim Spector, Professor of Genetic Epidemiology at King’s College London, Consultant Rheumatologist and Director of the Department. “Twins were coming in for one test and we realised it would be more cost-effective to do a range of tests in one visit. No other unit in the country is doing this.”

As the Department began with a focus on osteoporosis and osteoarthritis (diseases of ageing that tend to affect women more than men), almost 80 per cent of the 11 000 twins on the register are female. Now, the Department welcomes twin volunteers of either sex, from the age of 16. Over the past 15 years, the researchers have studied the influence of genes on all kinds of diseases, characteristics and behaviours (see box for a selection of key findings). Over 3000 such phenotypes are under investigation.

“The last 15 years has really been sorting out the nature/nurture debate,” says Professor Spector. “The default position now is that everything is partly genetic until proven otherwise. It seems that nothing is off-limits to what can be genetically programmed: from political views to religion…you feel like nothing is sacrosanct.”

Now, the direction of twin research is reflecting wider changes in the field of genetics. According to Professor Spector, the Department’s next phase of research is to find the genes responsible for various diseases or characteristics. To do this, researchers will use the latest technologies, allowing large-scale genetic association studies that can flag most of an individual’s 23 000 genes.

It was researchers at the Department who performed the first genome-wide association scan for osteoporosis. They found two genes that increase a person’s risk of the disease 1.5-fold when present together. These genes are common and are thought to occur in around a quarter of women. Another recent study found that 14 per cent of men carry two genes that increase the chance of baldness seven-fold.

A twin-only meeting in support of Wellcome Collection’s ‘Divided Yet Whole’ event brought together twins from the TwinsUK registry

A twin-only meeting in support of Wellcome Collection’s ‘Divided Yet Whole’ event brought together twins from the TwinsUK registry

Another development is the emergence of the study of epigenetics, heritable changes in the way genes work that are independent from the DNA sequence itself. To explore epigenetics, twin researchers are now focusing on the differences between identical twins, a contrast to ‘traditional’ twin research, which had always been about comparing the similarities of identical twins with those of non-identical twins.

“Epigenetics is where identical twins come into their own,” says Professor Spector. “Preliminary results show tiny [epigenetic] differences between identical twins, and we’re looking at whether these changes are systematic, random or influenced by environment, and whether they change as people age.”

The researchers are looking across the genome to see whether twins have the same changes at sites called CpG islands – areas on the DNA chain where a guanine base directly follows a cytosine. At these sites, a small chemical group can be added in a process called methylation. The team will explore whether these changes affect particular genes’ being ‘on’ or ‘off’, and will study whether the methylation status of these sites changes as twins get older.

With these changes in mind, does Professor Spector ever see a time where twin research is no longer relevant? “Twin research is constantly changing. The nature versus nurture aspect will eventually have answered every question you could ever ask,” he says. “However, I think using the twin model to study other areas like epigenetics, copy number variation [genetic mutations involving the gain or loss of chunks of DNA, some of which are associated with disease] and even trials exploring individual genetic responses is going to keep twin researchers happy, certainly for the next 50 years.”

As part of securing the UK’s future as a leading place for twin research, Professor Spector is currently in discussions with the Department of Health to try to get an official twin register for the UK, which is one of the only northern European countries not to have one.

Back in the consulting room, our tests are finished. It’s with an odd sense of detachment that we pore over the printouts from the bone scanner, which reveal gawky-looking skeletons surrounded by fuzzy outlines of flesh. The detail is quite amazing, and the printouts give us information on not just our bone density but also the fat and lean mass of each body part, limb by limb. We learn that our bone densities are within normal levels and that we are not at an increased risk of fracture.

As Katie and I wander along the bright corridors of St Thomas’, we enjoy a glow of satisfaction at having done our bit for medical science, and imagine the future publications in which the data from our tests might feature. However, as interesting as it’s been, and despite the researchers’ reassurances, I’m still left with a sense of discomfort – it will take me some time to accept that my left arm has 4.1 per cent more fat than my right, and that I’m only average at gripping.

In your genes?

Work at the Department of Twin Research has increased our understanding of the genetic basis of many diseases of ageing, including osteoporosis and osteoarthritis. It has also shown that genetic factors play a part in a wide range of characteristics and behaviours – ranging from diet choices to the number of sexual partners a female has, from male-pattern baldness to becoming self-employed.

Other selected findings include:

  • moderate drinking (an average of eight units of alcohol a week) appears to keep brittle bones at bay in women
  • body odour is largely genetic and unique to individuals
  • having a high number of moles, exercising in your free time, and high vitamin D levels are all linked to delayed ageing (defined as having longer telomeres – the DNA caps that protect the ends of chromosomes from damage)
  • obesity and cigarette smoking accelerate human ageing (as measured by telomere length)
  • short-sightedness, cold intolerance, back pain and musical pitch recognition are predominantly genetic.

The Wellcome Trust has supported the Department and its core work on the TwinsUK resource since its launch in 1993. Other Trust-funded projects currently underway include studies covering the genetics of short-sightedness, how obesity genes are expressed differently in fat, muscle and blood, and the genes involved in age-related telomere variation.

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