Scientists are turning to genomic research to uncover the roots of major diseases like cancer but they’re doing it in a surprising manner: By focusing on the possible genotypes associated with these major diseases, even among patients that currently exhibit no disease symptoms. This basically entails using genome sequencing to look for markers in one’s genome to see if they are predisposed for a disease and take measure before it develops.
Genomic disease research is a radical departure from the standard approach to understanding and treating disease, its proponents say. Normally, doctors start with people that have received a disease diagnosis: A patient with a malignant tumor, for example, is diagnosed with cancer. Doctors attempt to identify the cancerous cells and eliminate them with radiation and chemotherapy.
The problem? This “reactive” approach to disease – especially cancer – may come far too late in its development for a medical treatment to reverse its course.
What do genomic researchers suggest instead? Study healthy asymptomatic patients to identify genomic patterns associated with major diseases, and then eliminate or alter those genetic patterns to pre-empt the disease before it actually develops.
It sounds a bit like finding a needle in the proverbial haystack. But 13 peer-reviewed studies have adopted this “preventative” approach to disease that focuses on the genetic structure of ostensibly “healthy” individuals. The results of those 13 studies, summarized in an article published in the American Journal of Human Genetics, suggest that genomic researchers may be on to something.
One study found that the traditional approach to studying disease tended to miss some of its important underlying genetic traits, largely because doctors, operating with their own preconceived notions of the disease, were focused only on its most obvious clinical symptoms.
For example, one NIH study found that having more than two copies of the TPSAB1 gene was associated with symptoms related to the gastrointestinal tract, connective tissues, and the nervous system.
In another study, researchers identified a person with a genomic variant associated with a known metabolic disorder. Additional testing revealed the presence of high levels of certain chemicals in the patient’s body that were closely associated with the disorder even though the patient exhibited only minor symptoms. Doctors might decide to treat patients with those high chemical levels, thereby pre-empting the possible development of a metabolic disorder, the study argued.
Genomic scientists aren’t necessarily suggesting adoption of this approach indiscriminately to all diseases, or without some additional evidence of an incipient disease condition. But with the addition of genomic research, a much larger pool of prospective disease candidates can be identified and a wider range of early treatment options discussed to potentially stave off the development of a major disease.
“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” says Caralynn Wilczewski, Ph.D., a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core who co-authored one of the 13 studies.
Wilczewsi’s study – like other 12 reviewed – drew upon genomic data stored at NHGRI’s Reverse Phenotyping Core in the Center for Precision Health Research. To date, more than 16,000 research participants have undergone genome or exome sequencing making which means an unusually robust pool of candidates is available for future testing – and validation – of the “genotype-first” approach to disease study.