Genome’s capacity to predict is limited

“The punch line is that this sort of personalised medicine will not in any way be the most important determinant of patient care,” said Dr Bert Vogelstein of Johns Hopkins,who,with his colleagues and his son Joshua,analysed the power of sequencing all of a person’s DNA to determine an individual’s risk of disease.

The study,published online Monday in the journal Science Translational Medicine,involved data from 53,666 identical twins in registries from the United States,Sweden,Finland,Denmark and Norway. The registries included data on 24 diseases,telling how often one twin,both or neither got a disease. Since identical twins share all of their genes,the investigators could ask to what extent genes predict an increased chance of getting a disease. Using a mathematical model,they reached an answer: not much. Since identical twins share all of their genes,the investigators could ask to what extent genes predict an increased chance of getting a disease. Using a mathematical model,they reached an answer: not much. Most people will be at average risk for most of the 24 diseases.

They asked: Would those who ultimately got one of the 24 diseases have been forewarned by DNA sequencing? “Unfortunately,it tells them they are at roughly the same risk as the general population,” Vogelstein said.

The researchers also asked whether healthy people would learn by DNA sequencing that they were at low risk for a disease. Again,the results were disappointing. For example,more than 93 per cent of women would learn they were at low risk for breast cancer and more than 97 per cent of men and women would learn their risk for lung cancer was low. “But these negative tests do not mean they are at no risk for these cancers,” Vogelstein said. Their risk is more like that of the general population.

And,Vogelstein said,even knowing you are at high risk for a disease may be less useful than it sounds. A woman who is at high risk for ovarian cancer might have a 10 per cent risk,many times higher than average. That,Vogelstein said,“is unlikely to be the main determinant of her health.”

But there was one positive finding—as many as 90 per cent of people would learn that they are at high risk of getting at least one disease. And gene sequencing could,in theory at least,identify as many as 75 per cent of those who will develop Alzheimer’s disease,autoimmune thyroid disease,Type 1 diabetes and,for men,heart disease.

However,with the exception of heart disease,there is as yet no way to prevent these diseases or slow their progress. And since high risk of an infrequent disease,like ovarian cancer,is far from a prediction that the disease is in the person’s future,the information might be valuable but would not

necessarily make much difference in the end.

“The general point is absolutely correct,” said Dr David Altshuler,professor of genetics and medicine at Harvard Medical School,who was not involved with the research. “Even if you know everything about genetics,prediction will remain probabilistic and not deterministic.”

Other experts pointed out different aspects of DNA sequencing that can improve health and medical care. Sequencing can,in some cases,aid in determining a patient’s prognosis. It can find the causes of mystery ailments in individuals,and it can find mutations that appear to be driving the growth of cancers in individual patients. Sequencing also is starting to help doctors decide who should take drugs to prevent diseases,as is happening with heart disease.

In heart disease,one pressing problem is how to decide which young and middle-aged adults would benefit from cholesterol-lowering statins to reduce the risk of a first heart attack,said Dr Sekar Kathiresan,a genetics researcher who is director of preventive cardiology at Massachusetts General Hospital. The drugs reduce the risk by 20 per cent,but if your risk is low to start with,a 20 per cent reduction does not mean much.

Now,Kathiresan said,by analysing data from studies that sequenced entire genomes,researchers have found 30 gene variants that,taken together,can identify healthy people who have twice the average risk of heart disease. “There is a great attraction to using genetics in this way,” he said. Robert Cook-Deegan,professor of law,ethics and policy at Duke,notes that every person whose DNA is sequenced will get information about whether he or she will respond to certain drugs and whether certain side effects will result from taking certain drugs. Vanderbilt University is doing genetic analyses of patients to help in prescribing a short list of drugs,said Dr William Schaffner,chairman of the department of preventive medicine at its medical school.

But the real benefit of studying the human genome,Altshuler said,is not to predict people’s medical futures but instead to understand how diseases occur and to use that knowledge to develop better therapies. Already this sort of work has succeeded with an entirely new type of drug to lower levels of LDL,or “bad” cholesterol,he said.