Whole Genome Testing Not Always Good At Predicting Diseases
April 4, 2012

Whole Genome Testing Not Always Good At Predicting Diseases

Researchers at John Hopkins University found that whole genome sequencing may not help most people find out whether their at risk for common diseases or not.

The team reported online in the journal Science Translational Medicine that they doubt whole genome sequencing can reliably predict the majority of future medical problems that may occur in a person's life.

During the research, the John Hopkins team used data from thousands of identical twins.

On average, any two individuals' genomes differ in 4.5 million positions scattered throughout their genomes.  Whole genome sequencing identifies those differences, and links them to known or suspected contributions to an individual's risk of certain diseases.

Identical twins share the same genome, and if the genome were a determining factor for common diseases, then the prevalence of a specific disease in an individual whose twin has that disease can be used to help determine how well whole genome sequence can predict diseases.

The researchers collected information on the incidence of 24 diseases among the twin-pair groups, including cancer, autoimmune, cardiovascular, genitourinary, neurological and obesity-associated diseases.

They used mathematical models developed by researchers at the university to help predict the disease risk.

The math models were used to calculate the capacity of whole genome sequencing to predict the risk of each disease based on typical thresholds used by doctors to initiate preventative or therapeutic measures.

They found that whole genome sequencing could alert most individuals to an increased risk of at least one disease, but most people would get negative test results for the majority of diseases studied.

Kenneth Kinzler, Ph.D., co-director of the Ludwig Center at Johns Hopkins and professor of oncology, reports that as many as two percent of women undergoing whole genome sequencing could receive a positive test result warning them of ovarian cancer.  This result, he said, alerts them that they have at least a one-in-ten chance of developing that cancer over their lifetime.

The other 98 percent of women who receive a negative test for ovarian cancer still have a risk the same as the general population, Kinzler said.

"So, a negative test is not a 'free pass' to discount the chance of acquiring any particular disease," he said in a press release.

The team said their analysis specifically shows that whole-genome-based tests are not highly informative for predicting cancer.  However, they did find that genetic test could identify more than three-quarters of patients who may develop coronary heart disease, thyroid autoimmunity, type 1 diabetes and Alzheimer's disease.

"In families with strong histories of cancer, whole genome sequencing can still be very informative for identifying inherited genes that increase cancer risk," Victor Velculescu, M.D., Ph.D., who worked on the study, said in a press release.

"But hereditary cancers are rare. Most cancers arise from mutations acquired through environmental exposures, lifestyle choices and random mistakes in genes that occur when cells divide."