Drug Adherence Tied to Genetic Influences, Not Side Effects

By Megan Brooks

September 03, 2021

NEW YORK (Reuters Health) - A study looking at genetic and environmental determinants of drug adherence may help in identifying patients at high risk of non-adherence to prescribed therapy.

The results suggest that adherence pertains more to an individual's genetic predisposition to particular behaviors than to underlying biological factors such as the adverse effects of a specific drug, the researchers conclude.

"The findings will allow for better identification of patients at higher risk of low adherent drug-taking behavior," Mattia Cordioli, a PhD student at FIMM, the Institute for Molecular Medicine Finland, in Helsinki, told Reuters Health by email.

The study was presented at the European Society of Human Genetics (ESHG) annual meeting.

How well people stick to a prescribed drug treatment is clearly a key factor in efficacy of a drug regimen. Behavioral and socioeconomic factors are known to affect adherence, but less is known about the role played by genetics.

To investigate, Cordioli and colleagues leveraged genetic data from the FinnGen study with more than 260,000 participants, as well as data from Finnish national health registries and the drug purchase registry.

For each individual drug-trajectory, the researchers used information on the date that the individual purchase was made, and the quantity purchased, to define adherence by dividing the initial quantity by the number of days, with reference to the prescribed daily dose.

For each medication, they then ran a genome-wide association study (GWAS) to see if genetic variants might help explain variations in adherence.

Overall, the results suggest that drug adherence was related to genetically influenced behavioral traits.

"We found that a positive genetic correlation between adherence and other traits, for example, educational achievement, meant that individuals with a genetic predisposition for higher educational achievement tended to be more adherent. On the other hand, those with a genetic predisposition for risk-taking were less adherent to the medication schedule," Cordioli said in a news release.

In addition, while a genetic predisposition for higher systolic blood pressure correlated with increased adherence to blood pressure medication, there was no such association in patients with a predisposition for higher LDL cholesterol and statin adherence.

"The fact that, for example, statins adherence shows more correlations with behavioral and psychological traits is not surprising per se. The results were surprising in the sense that, for example, we could have expected genetic variants that play a role in reducing statins response or increasing the risk of side effects to also affect adherence, but it does not seem to be the case," Cordioli told Reuters Health.

Drug adherence was also positively correlated with a genetic predisposition for type-2 diabetes and higher BMI, suggesting that patients in higher risk categories tend to be more adherent.

Demographic and socioeconomic factors are important in drug adherence but studying individual genetics may help reveal possible biological mechanisms affecting adherence, the researchers say.

"Our research has shown that adherence pertains more to an individual's predisposition to a particular behavior rather than to underlying biological factors such as the adverse effects of a particular drug. We are hopeful that the identification of those patients who are less likely to adhere to drug therapy may encourage and facilitate the design of effective information campaigns directed at them," Cordioli said in the news release.

"Along with the advances in genetic testing that can show how an individual responds to drugs and therefore allow the prescription of tailored treatment, we believe that further biological investigations into individual adherence may make a valuable contribution to the design of new standard clinical practice in the future," he added.

In the news release, ESHG conference chair Dr. Alexandre Reymond, director of the Center for Integrative Genomics at the University of Lausanne, Switzerland, said, "Adherence to a prescribed treatment has not previously been looked at from a genetic point of view and finding that this is potentially more linked to behavior than to adverse effects gives us clues on where the health system should put its efforts to gets the best results."

The study had no specific funding and the authors have no relevant disclosures.

SOURCE: https://2021.eshg.org/ European Society of Human Genetics annual meeting, presented August 30, 2021.