A massive genetic study carried out in the United Kingdom has pinpointed 24 genetic markers that increase risk for illnesses such as diabetes, arthritis, and Crohn’s disease, a form of inflammatory bowel disease. The findings illustrate the success of a new approach to gene hunting known as genome-wide association, made possible by recent advances in gene-sequencing technologies. The results were published in this week’s issue of Nature.

“This is a powerful way of identifying genes for common diseases,” says Anne Bowcock, a geneticist at Washington University Medical School, in Saint Louis. “These genes will point to altered pathways that will then point to novel therapies.”

Scientists analyzed 500,000 genetic markers in each of 17,000 people, making it the largest such study to date. By comparing the DNA of 2,000 patients with one of seven different diseases–Crohn’s disease, type 1 and 2 diabetes, cardiovascular disease, hypertension, rheumatoid arthritis, and bipolar disorder–with 3,000 healthy controls, researchers identified 24 genetic regions strongly linked to specific diseases: one in bipolar disorder, one in coronary-artery disease, nine in Crohn’s disease, three in rheumatoid arthritis, seven in type 1 diabetes, and three in type 2 diabetes. Known as the Wellcome Trust Case Control Consortium, the project is a collaboration among 50 different research groups.

Unlike diseases such as Huntington’s, in which a single genetic marker guarantees that the carrier will develop the disease, common diseases are triggered by a complex array of factors, including multiple genes each exerting a modest effect. Unlocking their genetic secrets has been a challenge, but recent advances in gene-sequencing technology have allowed scientists to take a new approach to gene hunting. Rather than searching through the DNA of specific target genes or afflicted families–approaches that have had little success for common diseases–scientists are scouring the entire genomes of large numbers of people.

By examining the entire genome, scientists find genes they never expected would be involved in a particular disease. And the massive size of such studies–the Wellcome study, for example, included almost 10 billion pieces of DNA–gives the statistical power needed for researchers to find genetic variations that raise the risk of disease by a modest amount.

In this case, scientists used a gene chip developed by Affymetrix, a genetic technology company based in Santa Clara, CA. The gene chip assesses 500,000 genetic markers in a single experiment. By comparing genetic variations in healthy people with those of people with the disease of interest, scientists can pinpoint genes that boost a person’s risk of the disease by as little as 20 percent.

One of the earliest success stories to arise from genome-wide association has involved Crohn’s disease, a painful intestinal disorder. Crohn’s has a strong genetic component–someone with a sibling with the disease has a 30 percent increased risk of developing it. Several risk genes have already been uncovered, including a gene involved in inflammation.

The Wellcome study identified additional Crohn’s genes, two of which were quite a surprise to scientists. They code for proteins involved in autophagy, a process by which a cell clears bacteria and other waste. “We had no reason to suspect autophagy to play a role [in Crohn’s] before these results came out,” says Miles Parkes, a gastroenterologist at the University of Cambridge, who confirmed the findings in a companion paper published today in Nature Genetics. “Now we know this pathway is very important to disease–it’s another triumph for the hypothesis-free approach.”

In another unexpected finding, scientists identified a gene that increases risk for type 1 diabetes and Crohn’s disease, which are both autoimmune diseases. Scientists hope the newly discovered link between the two diseases will speed development of new treatments. “The pathways that lead to Crohn’s disease are increasingly well understood and we hope that progress in treating Crohn’s disease may give us clues on how to treat type 1 diabetes in the future,” said John Todd, a researcher at the University of Cambridge, in a statement released by the Wellcome Trust. Todd led a companion study confirming the diabetes results published today in Nature Genetics.

Results from the Wellcome Trust follow those from several other studies released over the past few months, identifying genes linked to Crohn’s, diabetes, and cancer. Additional studies involving large-scale genome tests are under way in the United States. They will likely identify new genetic variants and confirm those that have already been discovered.

In fact, according to the Wellcome study, even larger numbers of participants may be needed to identify genetic markers for diseases linked to a greater number of genes, each exerting a small effect, such as bipolar disorder, or disorders that do not seem to arise from a small number of genetic factors, such as hypertension.