SAN DIEGO (GenomeWeb News) – While genome-wide association studies have long been considered an avenue for improving diagnostics, prognostics, and treatment, their most immediate application appears to be for improving drug safety and decreasing adverse events, according to Lon Cardon, senior vice president of GlaxoSmithKline's genetics program.
Speaking at the American Association for the Advancement of Science annual meeting held here, Cardon described how an improved appreciation of human genetic variation is being applied to drug safety problems.
Despite a slow start in identifying disease-associated genes, Cardon explained, the advent of new genomic technology coupled with research in different human populations has yielded hundreds of published, validated genome-wide associations — and a better appreciation for the magnitude of variation in the human genome.
"The field didn't just incrementally change, it transformed itself," Cardon said during a session this past weekend.
Even so, he noted, most variants detected in GWAS don't have a large enough effect to be considered clinically actionable since most have individually small effects.
For instance, even for type 2 diabetes — which Cardon calls a "stunning success area for genome-wide association studies" — the biggest risk variants found to date don't raise diabetes risk enough to catch epidemiologists' attention, he said.
Indeed, recent studies in the British Medical Journal and the Journal of the American Medical Association, respectively, reported that traditional clinical information is still more clinically useful for predicting type 2 diabetes or heart disease risk than models based on the genetic variants identified to date.
In contrast, Cardon argued, researchers have had far more success in translating GWAS success into clinical applications when it comes to understanding drug safety issues — particularly predicting adverse events and improving treatment efficacy.
Using the genetics of abacavir hypersensitivity as one of several examples, he explained that genetic variants linked to adverse drug events have already helped to change treatments and decrease negative outcomes.
While he didn't rule out the possibility that GWAS data will have a range of other clinical applications related to disease diagnoses and prognoses, Cardon argued that the promise of this sort of data for improving drug safety is already being realized.
And with more and more pharmacogenomics studies underway, genetics may play an even greater role in drug prescribing down the road. In particular, Cardon pointed to the creation of the Severe Adverse Events Consortium, or SAEC, a non-profit group consisting of academic researchers, regulators, and representatives from the pharmaceutical industry that was established several years ago to explore the genetics of drug response.
SAEC released its initial findings on the genetics of Stevens-Johnson syndrome early last year. The group has since participated in studies identifying variants linked to drug-induced liver injury related to the use of the antibiotic flucloxacillin.
More recently, SAEC announced collaborations with the HMO Research Network to explore the possibility of using HMORN's clinical data to study drug-related serious adverse drug effects. They are also partnering with researchers at Duke University to look for rare variants corresponding to adverse reactions to the antipsychotic drug clozapine, according to GenomeWeb Daily News sister publication Pharmacogenomics Reporter.