"It's certainly been interesting," said Quake of the findings. "I was curious to see what would show up. But it's important to recognize that not everyone will want to know the intimate details of their genome, and it's entirely possible that this group will be the majority. There are many ethical, educational and policy questions that need to be addressed going forward."

Of course, a person's environment ” in the form of choices he or she makes about diet, exercise and habits like smoking and drinking ” can also powerfully affect disease risk. But if clinicians know that a patient has a higher-than-normal risk for a certain disease, they may recommend certain lifestyle changes more strongly.

"This opens the door to targeted environmental interventions based on a patient's genomics," said Butte. "People who may want more control over their destiny could choose to exercise more, or eat better, or even avoid pesticides more conscientiously."

There's hope, too, in the promise of more effectively using available drugs to combat or prevent disease. Russ Altman, MD, PhD, is the principal investigator of the Stanford-managed Pharmacogenetics and Pharmacogenomics Knowledge Base, or PharmGKB ” a curated, international data repository to help researchers understand how genetic variation among individuals contributes to differences in reactions to common medications. Quake's genome gave his group some new opportunities.

"With Steve, we thought, 'Let's apply everything we know about the effect of human genetic variation on drug response to his entire genome,'" said Altman, who together with Quake chairs Stanford's bioengineering department. "And we came up with a table of drugs that are likely to work well for him, like statins, and others that he might need lower doses of, like warfarin."

The researchers also found five to 10 previously unknown SNPs in genes involved in drug response. "This is really exciting because we never would have found these if we'd just relied on our usual panel of suspects," said Altman. "What's more, with whole-genome sequencing, you only ever have to do it once. Our understanding of the information will keep evolving, but the core data set doesn't change."

That evolving knowledge base will present a particular challenge, the researchers believe. Keeping people up-to-date on new findings involving genetic variants that they carry will be a tricky business. Clinicians of the future will walk a tightrope of informing people who've opted to have their genome sequenced of ongoing discoveries while also presenting the information as uncertain and likely to change. Furthermore, how shall we deal with the fact that a patient's genome by definition harbors information about that person's parents, children and other relatives who may not want to peek into their shared genomic crystal ball? Clearly we have much with which to grapple.

"The world of medicine is going to change beyond belief," said Ashley. "We are all going to have to learn how to deal with questions like these."

But what of Quake?

A complete physical pronounced him free of any sign of cardiomyopathy. But it also turned up somewhat elevated lipoprotein levels. Normally, given Quake's health and age, most physicians would take a watch-and-wait approach before recommending medication. However, in the face of this new information about Quake's lifetime genetic risk, and the likelihood, based on the pharmacogenetic data, that he would respond positively to statins, Ashley suggested he consider taking the cholesterol-lowering drugs. It's the first time anyone's ever made clinical recommendations based on a cumulative assessment of a patient's entire genome.

And so it begins.

SOURCE Stanford University School of Medicine