Seattle scientists have identified three new genes linked to obesity, using a novel research technique that could be widely applied to other genetic analysis.

Two of the genes, discovered in mice, someday could be targets for human obesity-prevention drugs, said Eric Schadt of Rosetta Inpharmatics, a Seattle biotechnology company where the research was centered.

"It will stimulate a lot of activity in exploring the genes and how they work," said Schadt, senior scientific director for Rosetta, owned by Merck.

The new findings are reported in this month's edition of the journal Nature Genetics.

Further research could lead to important new ways to treat one of the most difficult medical problems around. Being overweight or obese can increase the risk of a variety of diseases and conditions, including diabetes, coronary artery disease, respiratory problems and certain cancers.

Almost all the genes that so far have been linked to human obesity, including 20 to 30 that have been explored as drug targets, were discovered in rodents, Schadt said. At least two drugs already are on the market.

About 56 genes have been linked to obesity in lab animals, but only about 10 are accepted widely as having any influence in humans. Those most explored are concerned with the hormones ghrelin, which stimulates appetite, and leptin, which helps regulate how much fat is stored in the body.

Finding genes that can be influenced with drugs to prevent obesity is complex because many different genes, as well as environmental and behavioral factors, may contribute to each individual's obesity.

The genes discovered by Schadt and his colleagues already are known for their involvement in other functions: inflammation, tumor growth and cell replication. But the scientists don't know yet why they were connected to obesity in the laboratory mice. Once they learn that, they will work toward developing a drug, Schadt said.

The researchers also confirmed that another gene, discovered two years ago by Harvard scientists, is indeed linked to obesity in lab mice.

The research used a new system for analyzing genetic activity. Called DNA microarray analysis, it uses computers to observe thousands of genes at once. That way, researchers can determine which genes are "expressing," or producing new proteins.

Rosetta scientists also used a technique they developed to determine how DNA differences in the same gene cause differences in the way the genes express in different individuals.

"It will make an association between the gene and disease much faster," said Schadt.

Dr. Malcolm Low, an obesity researcher at Oregon Health & Science University, praised the methods used by the Rosetta scientists. By looking at a huge array of genes at once, the researchers had no preconceptions about which genes might be involved in obesity.

"I think that is really the way to find something new," Low said.

The Rosetta researchers analyzed the genes of 111 mice. Some were the offspring of obese mice, some of lean. The newly found genes were more active in the obese mice.

Schadt said the scientists next will try to learn how the genes influence obesity. That could lead to discoveries of other genes that work in the same way. The process could take up to two years before efforts to design a drug to impact the genes could begin.

Two obesity drugs already on the market work in different ways. One blocks fat absorption; the other works on the brain's appetite-control centers. Another, still under development, also operates as an appetite suppressor.

The market for a new drug, of course, would be huge. About 30 percent of U.S. adults — more than 60 million people — are considered obese by the federal Centers for Disease Control and Prevention. And more than 9 million youths are considered overweight.

Collaborating with Rosetta in the new findings were scientists at Oklahoma State University, UCLA, Merck Research Laboratories in New Jersey and Deltagen of San Carlos, Calif.

Warren King: 206-464-2247 or wking@seattletimes.com