Predicting the Risk for Five Deadly Diseases

New Algorithm Surveys Alterations in DNA and Millions of Points in the Human Genome

Scientists have created a powerful new tool to calculate a person’s inherited risks for heart disease, breast cancer, type 2 diabetes, chronic inflammatory bowel disease, and atrial fibrillation.

By surveying changes in DNA at 6.6 million places in the human genome, investigators at the Broad Institute and Harvard University were able to identify many more people at risk than do the usual genetic tests, which take into account very few genes. Of 100 heart attack patients, for example, the standard methods will identify two who have a single genetic mutation that places them at increased risk. But the new tool will find 20 of them, the scientists reported in Nature Genetics.

The researchers are now building a website that will allow anyone to upload genetic data from a company like 23andMe or Users will receive risk scores for the five aforementioned diseases. A risk score, including obtaining the genetic data, should cost less than $100, according to Dr. Daniel Rader, a professor of molecular medicine at the University of Pennsylvania. Dr. Sekar Kathiresan, senior author of the new paper and director of the Center for Genomic Medicine at Massachusetts General Hospital, said his team had validated the heart risk calculation in multiple populations.

The new tool also can find people at the low end of the risk range for the five diseases. This should prove useful to certain patients: for example, a woman who is trying to decide when she should start having regular mammograms, or a 40-year-old man with a slightly high cholesterol level who wants to know if he should take a statin.

The study began because there was general agreement among researchers that many common diseases are linked not to one mutation, but rather to thousands or millions of mutations, said the first author of the new paper, Dr. Amit V. Khera, a cardiologist at Massachusetts General Hospital and a researcher at the Broad Institute.

In recent years, scientists have cataloged more than 6 million tiny changes in DNA that slightly affect the chances that people will get various diseases. Each of those genetic alterations has such a small effect—approximately a 1 percent increase or decrease in a person’s odds of getting a disease — that it would not be helpful to test for each one in isolation. But it should be possible, scientists felt, to combine data on all of the small DNA changes to construct an individual risk score. To do that, the researchers needed a new algorithm that would weigh the significance of the variations in the genes.

Then they had to test the risk scores they obtained. Dr. Khera and his colleagues turned to the U.K. Biobank, which holds genetic and disease information on half a million people. The investigators found that their algorithm did predict the odds of being diagnosed with one of the five diseases. But because the U.K. Biobank consists mostly of white Europeans, the investigators also tested and validated their method in populations of East Asians, South Asians, African Americans and Hispanics. The researchers also tried their algorithm on 20,000 patients  at Brigham and Women’s Hospital and Massachusetts General Hospital. They found that those who had a high-risk score for a heart attack were indeed four times more likely to have had a heart attack than other patients.

At the University of Pennsylvania, doctors will incorporate risk scores on heart attacks into advice to patients on preventive care.

Source: The New York Times, August 13, 2018