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A Large-Scale Twin Study Aims to Elucidate Common Disease

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A large-scale epigenetic study of common diseases in twins, particularly those discordant for a disease, may provide new targets for therapy.

"Identical twins and epigenetics are the ideal partners because we know there's both genetic effects and environmental effects," says Timothy Spector of King's College London. "In non-twin populations, you'd have to do studies that were perhaps 10 to 20 times as large to find the same results."

TwinsUK, Spector's research group at King's College, is teaming up with BGI to study the epigenetics of common diseases in about 3,000 monozygotic twins and 2,000 dizygotic twins using methylated DNA immunoprecipitation coupled with next-gen sequencing, or MeDIP-seq. This approach gives about 25 million CpG sites, Spector says.

For this project, the team is focusing on age-related diseases like type 2 diabetes, depression, and heart disease, among other common public health issues, and is drawing on DNA and phenotype data collected during the past 20 years by TwinsUK. Spector and his team took a broad approach to their collections over the years. "Anything that's common, we collect — everything from dietary information to personality, behavioral questions to range of diseases, drugs, medications," he says. "We are trying to pick things that are related to generally complex, common age-related traits."

Spector presented the results of the group's pilot project on pain, which was funded by Pfizer, at the International Congress of Human Genetics/American Society of Human Genetics meeting in Montreal, Quebec, in October. "The main finding [was] replicating differentially methylated regions for experimental pain, and some of them are novel regions," he says. "We've identified as proof of concept that three of these regions contain major known pain candidate genes. So we are confident that we are going to find physiologically relevant signals."

The researchers are about halfway through the sequencing phase of the project, and are gearing up for the analysis stage. "Potentially, we have the ability to do a thousand individual studies of each disease or trait. We are prioritizing it depending on where our funding is coming from, or public health interest, or commercial interest," Spector says.

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