Twin research at St Thomas' Hospital 13/5/03. By Deirdre Janson-Smith The UK's largest twin database is exploring the role of genes in complex diseases.

The Twin Research and Genetic Epidemiology Unit at St Thomas' Hospital in London, UK, was established in 1992 to explore the role of genes in complex diseases, including osteoporosis, arthritis, heart disease, diabetes and asthma.

St Thomas' has the UK's largest database of twins, and is the most detailed cohort of adult twins in the world – with hundreds of measurements for each twin. For Professor Tim Spector, Director of the Unit, this represents an important resource for researchers. "We already have huge amounts of data on all our twins: 300 measures ranging from sense of humour to leptin levels, with the potential to gather much more. And we have a whole genome scan for 3000 twins (1500 pairs). It's an exciting resource for the future."

By studying the twins, researchers aim to discover ways in which genes influence a large number of common diseases. "Comparing similarities between identical and non-identical twins produces important information on the extent to which a disease is caused by genes or the environment," says Professor Spector.

"Studying twins cuts down the 'noise' created by individual differences in environment and life experiences," agrees colleague Professor Alex MacGregor. "There is no other situation where you can control simultaneously for genetic background, sex, birthdate, pre-and post-natal environment and a host of other environmental factors."

"Once you've pinpointed the genes responsible for a certain disease you can do two things," says Professor Spector. "First, you can develop a diagnostic test predict the risk of someone getting the disease - and take steps to reduce their risk. Second, by discovering the genes you will discover new chemical pathways in the body, which are targets for new drug development and novel treatments."

Twin studies offer features that uniquely enhance our ability to localise genes and understand their function. In the past, for example, medicine has relied on epidemiological studies of large, mixed populations to study complex diseases such as cancer and heart disease. But, for such slowly-developing diseases, understanding what combination of factors are at work is, says colleague Professor Alex MacGregor, "like looking for a needle in a giant haystack. Twin studies reduce the amount of hay – cutting down the 'noise' created by individual differences in environment and life experiences. There is no other situation where you can control simultaneously for genetic background, sex, birthdate, pre-and post-natal environment and a host of other environmental factors."

Research St Thomas’ Hospital focuses on 'intermediate' factors that contribute to disease development, moving down a level in analysis to discover the body's pathways to illness. "In heart disease, for example, we can measure cholesterol levels, or look at individual clotting factors," says Professor Spector. "In osteoporosis, we can measure bone cell turnover. Studying the genes that control these underlying mechanisms allows us to get a much better handle on the disease."

"A novel future approach will be our studies of 'discordant identical twins' - twins where, despite sharing identical genes, one goes on to develop a disease, while the other appears to be free of it. We can ask what pathways are being activated in the diseased twin. Often, just a few twins give the vital clue."