Sharon Begley in StatNews:
For all the promises of genomics ushering in a new era in medicine, with scientists regularly urging people1 to get their DNA sequenced, it appears that the revolution will be postponed: A first-of-its-kind study2 published Monday found that most of the adults who underwent genome sequencing and were told they had a disease-causing DNA variant did not in fact have that disease. And few of them got information that improved their health. The pilot study, in the Annals of Internal Medicine, found that 11 out of 50 volunteers (aged 41 to 68) who had their genome sequenced were told they had a mutation that definitely or possibly causes a particular disease, ranging from pituitary thyroid insufficiency to the rare cardiovascular disorder Romano-Ward syndrome. Yet only 2 of the 11 actually had the disease, which in every case should have appeared by adulthood. “We were surprised” by the high incidence of disease-causing mutations, said Dr. Jason Vassy, of Brigham and Women’s Hospital in Boston, the study’s lead author. “But we were surprised even more” by how few people with “disease-causing mutations” had the disease.
Whole genome sequencing3 reads the nearly 3 billion chemical “letters” — the A’s, T’s, C’s, and Gs — that constitute an individual’s DNA. Some geneticists envision genome sequencing as a way to identify everything from what drugs an individual should avoid (if he has the DNA variant that makes statins dangerous to him) to what diseases her doctor should screen for and possibly treat early. The MedSeq study put that hope to the test in the first-ever randomized trial of whole genome sequencing in adults. Volunteers were assigned, essentially by the flip of a coin, to either have their genome sequenced (and analyzed for the presence of DNA variants in 4,631 genes) or to have their family medical history analyzed. The 4,631 genes the researchers analyzed were those that, if mutated, are supposedly sufficient to cause a usually rare disease, such as ankyrin-B-related cardiac arrhythmia (caused by mutations in the gene ANK2). Such single-gene disorders are called Mendelian. The study did not include the thousands of genes that merely raise the chance of developing a disease to which many other genes contribute, such as the vast majority of cancers, heart disease, and psychiatric disorders. That should have stacked the odds so that an unearthed mutation really did cause disease.
The key finding — that few people with “disease-causing” mutations actually had a genetic disease — therefore raises questions about whether genome sequencing in generally healthy adults can be medically justified.