On Sunday, more than a thousand sets of twins from around Australia and the world will gather in Melbourne to celebrate the bond they share with their identical or fraternal twin.

The physical similarities of identical twins have always drawn interest from onlookers, but it’s only in recent decades that researchers have recognised the important role twins play in health and medical research.

Identical twins are genetically the same but their environments become more individual as they age. Studying identical twin pairs, therefore, gives insights into how the environment and genes interact.

This has become increasingly important when studying the complexities of health-related issues across an individual’s lifespan. When one identical twin develops a disease but the other doesn’t – or one twin adopts a particular lifestyle that’s completely different to the other – researchers can learn valuable information about environmental risk factors.

Non-identical or fraternal twin pairs are also important for research; they share, on average, 50% of their genes, just like other siblings who aren’t twins.

The most powerful twin studies gather data from both identical and non-identical twin pairs and compare similarities to find out if there is evidence for genetic factors in disease development. If identical pairs are no more similar for a particular characteristic than non-identical pairs, it becomes clear that the characteristic can’t be influenced by genetics.

Also, by studying mixed-gender twins, researchers can discover important information about the differences between the sexes. And comparisons across different types of twin pairs can be informative: a male member of a boy/girl pair shared the womb with a female sibling, while a male member of boy/boy pair shared the womb with a male sibling. This allows researchers to study the effect of different hormonal environments in the womb.

Twin insights in medical research

The Australian Twin Registry (ATR) is the largest voluntary twin registry in the world, with a membership of around 37,000 pairs of all ages. The registry has supported more than 450 twin studies since it was established 30 years ago, including leading research on epilepsy, smoking and epigenetics.

Epilepsy

Epilepsy is not one disease, but a large number of different conditions that can be categorised into groups.

By studying the similarities of identical and non-identical twins for epilepsies, researchers in the 1980s – headed by the University of Melbourne’s Sam Berkovic – worked out which groups of epilepsy conditions were likely to have a genetic basis.

This research was the first step in the identification of more than 20 different epilepsy genes which, when mutated, predispose to an inherited form of epilepsy. Knowing the normal functions of these genes gives insights into the biological mechanisms underlying hereditary epilepsy, with important implications for understanding causes, diagnosis and treatment.

Tobacco-related harm

Although if one twin smokes the other usually does, there are twin pairs who differ substantially in their smoking habits. In the 1990s, Professor Ego Seeman and I identified 20 female pairs in which one twin had never smoked and the other had smoked for more than 20 years.

We found that the smoking twins’ bones were on average 5% weaker – enough to double their risk of an osteoporotic fracture in later life. This provided compelling evidence that smoking causes osteoporosis.

Epigenetics

In the 21st century, twin research has moved into the field of epigenetics. Studies in this emerging discipline investigate the way in which environmental factors influence proteins and other molecules that bind to DNA, changing gene expression. Epigenetic effects have been linked to many diseases, such as cancer and psychiatric disorders.

Identical twin pairs provide a perfect control for underlying genetic make-up, so they are the best design for studying how the environment changes gene expression.

One innovative new Australian twin study, led by Dr Jeff Craig at the Royal Children’s Hospital in Melbourne, is investigating the role of epigenetics on conditions in infancy, such as asthma, by identifying twin pairs even before they are born. The researchers use ultrasound and obtain biological material at birth, then follow the twins up at regular intervals during their early lives.

International research

International collaboration between twin registries is making progress into research on rarer conditions, such as multiple sclerosis. The challenge is to find sufficient numbers of twin pairs, in which one or both have the disease, to enable meaningful studies.

No one twin registry can do this alone, so a new initiative instigated by the ATR is bringing the global twin research community together to develop an International Network of Twin Research. This will help researchers better understand how different environments across countries, and different genes across races, can impact on diseases.

For example, a study of the number of moles on the backs of adolescent twins was conducted in both Australia and the United Kingdom (more moles is an indicator of a greater risk of melanoma). The study found that while the environment influenced the average number of moles, genetic factors explained why white children differed so much in mole count. Furthermore, these appear to be the same genes in both countries and they act independently of sun exposure.

It’s estimated that around 2% of the total population is a twin. With the global population reaching seven billion, this means there are about 140 million twins in the world, providing a wonderful potential resource for future medical research.

The ATR is a national resource funded by NHMRC, under the custodianship of the University of Melbourne. With the increasing awareness of the value of twin research – the “power of two” – more researchers are wanting to conduct twin studies.

The Registry always welcomes new members of twin pairs, both identical and fraternal, of all ages and both sexes, who want to make a voluntary contribution to health and medical research. To register, click here or ring 1-800-037-021 free of charge.

Author:John Hopper: NHMRC Australia Fellow, University of Melbourne

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