Neil Osterweil

October 23, 2017

ORLANDO — A person's "omes" — the genome, microbiome, transcriptome, metabolome, proteome — and minute-by-minute variations in physiologic measurements can be used to create a personal health profile, which can help predict risk for illness and even identify undiagnosed disease, new research shows.

"We're trying to do data-driven health, meaning that we're collecting a lot of data about people while they're healthy and trying to understand and ideally predict what they're at risk for," said Michael Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford University in Palo Alto, California.

Dr Snyder — a journal-thumping evangelist for the power of individual data gathered from real-time monitoring — practices what he preaches.

"I have three smart watches, I have this ring that measures sleep and activity, a Moves app on my phone, two continuous glucose monitors, and a radiation monitor. All but one send information to my smartphone," Dr Snyder reported. He enthusiastically displayed some of his monitoring hardware to a group of journalists here at the American Society of Human Genetics 2017 Annual Meeting.

But he isn't just a gearhead. Dr Snyder and his colleagues are working to demonstrate that omic measurements and minute-by-minute variations in heart rate, blood pressure, glucose levels, and other physiologic factors can be used to generate "a detailed portrait of a person's healthy state and understand what changes when he or she transitions to a disease state."

Personal Omics

The investigators — using an approach they call "personal omics" — sequenced the genomes of 98 people with prediabetes, two with diabetes mellitus, and seven healthy control subjects, and collected longitudinal omes data. Activity levels and skin temperatures of the participants were monitored with wearable devices.

When a participant developed a respiratory viral infection, the investigators were able to monitor the dynamic changes that occurred as the patient got sick.

"We now think we can tell that people are getting sick before they know it, because their heart rates are elevated before they are symptomatic," Dr Snyder reported.

The investigators assessed the interplay between each individual's omic profile and his or her environmental stressors to see whether differences in the various subgroups could be identified.

"What we've found is that people who are insulin-resistant or diabetic don't respond to infections the same as people who are insulin-sensitive — the so-called healthy," Dr Snyder explained.

Immune and biochemical responses in insulin-resistant participants were measurably different than responses in insulin-sensitive control subjects. But whether such differences are related to outcomes is still unknown, he noted.

Detecting Undiagnosed Disease

In one case, a patient who had been clinically diagnosed with type 2 diabetes because of his insulin resistance actually had maturity-onset diabetes of the young, a genetic condition that affects an estimated 2% to 4% of people diagnosed with type 1 or type 2 diabetes. The condition is typically managed with diet and oral antidiabetic agents, and generally does not respond to exogenous insulin.

Two participants were found to have cardiovascular problems. In one patient, wearable monitors detected an arrhythmia and sleep apnea; in the other, risk alleles and a stress echocardiogram revealed dilated cardiomyopathy.

In addition, omic profiles were used to identify undiagnosed early-stage non-Hodgkin's lymphoma in one participant, and monoclonal gammopathy of uncertain significance, which is a precursor of multiple myeloma and some forms of leukemia, in another.

The investigators plan to continue tracking the current participants and to recruit new ones for a larger and more comprehensive cohort.

They also plan to evaluate the effect environmental and lifestyle factors have on a person's omic profile, and hope to develop predictive models that could be used to customize prevention and treatment plans.

A Costly Proposition

This work is currently for research purposes only. It would be far too costly — at more than $100,000 per patient — to implement the approach on a wide scale, Dr Snyder acknowledged. But he said that in the not-too-distant future, he envisions a "personal omics lite" version that costs significantly less — from several hundred to perhaps a few thousand dollars per person.

The most sophisticated test to measure insulin resistance "takes about 6 hours and costs thousands of dollars," he told Medscape Medical News. "We now have a molecular profile that could probably do it for about $50, because we know which compounds to look for to detect insulin resistance quite accurately."

For things to translate into medical care, somebody has to pay for them.

The underlying goal of this work is laudable, although it is not likely to show up in clinics any time soon, said Gail Jarvik, MD, head of the division of medical genetics at the University of Washington in Seattle.

An ounce of prevention is still worth a pound of cure. "Ben Franklin was exactly right, maybe now more than ever," she told Medscape Medical News. But it is unclear whether anyone will be willing to foot the bill for this prevention.

"Will we move to a technology where we can detect things using broad omics and prevent ill health? Absolutely," said Dr Jarvik. But "will it become cost-effective? I don't know."

"I think we're at a point right now where we're asking that question just of the genome, which has gotten to a reasonable price point." she added.

Insurers will usually not reimburse for genetic studies in patients with actionable mutations, or for diagnostic purposes when a genetic disorder is suspected, she explained.

"For things to translate into medical care, somebody has to pay for them. That's my concern," Dr Jarvik said.

This study was supported by grants from the National Institutes of Health and the Pew Charitable Trusts. Dr Snyder is a founder of and consultant for Personalis, a member of the scientific advisory board of GenapSys, and a consultant for Illumina. Dr Jarvik has disclosed no relevant financial relationships.

American Society of Human Genetics (ASHG) 2017 Annual Meeting: Abstract 278. Presented October 20, 2017.

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