Article Impact Level: HIGH Data Quality: STRONG Summary of European Heart Journal, ehac322. https://doi.org/10.1093/eurheartj/ehac322 Dr. Jonas Ghouse et al
Points
- The study identified seven (7) loci associated with ACEi discontinuation; of these, six (6) were new
- Five (5) lead variants were found to be associated with ACEI-associated cough; meanwhile, none were found for ACEI-associated angiodema
- ACEi discontinuation PRS is associated with ACEI-associated cough in a dose-response manner
- Identifying people at risk of eventually developing an ACEI-associated cough is possible through ACEi discontinuation polygenic risk prediction
Summary
This study aimed to address the concerns surrounding the genetic sequence variants of angiotensin-converting enzyme inhibitor (ACEi) discontinuation and its association with ACEI-associated adverse drug reactions (ADRs). Here, researchers studied 33,959 ACEi-discontinuers and 44,041 controls in a genome-wide association study (GWAS). Cases in the study were defined as those who switched to an angiotensin receptor blocker from an ACEi treatment; similarly, controls were defined as patients who continued ACEi treatment for at least a year. Results for this study were computed for ACEi discontinuation risk using mixed model regression analysis, while summary statistics were meta-analyzed for individual cohorts. ACEi discontinuation variants considered with genome-wide significance (p < 5×10-8) were tested for association with ACEI-associated cough and angiodema to assess association with ACEi-associated ADRs. An overall polygenetic risk score (PRS) was computed and tested for associated with ACEi-associated cough and angiodema in samples based on two populations; meanwhile, the overall score was based on ACEI discontinuation GWAS data.
Seven (7) genome-wide loci were identified as associated with ACEi discontinuation; six (6) of these were previously unreported. Of these, the strongest in association was at 20q13.3 (NTSR1; OR, 1.21; 95% CI, 1.17-1.24; p = 2.1×10-34). Five (5) of the seven lead variants were found to be associated with ACEi-associated cough, while none were found for ACEi-associated angiodema. ACEi discontinuation PRS was found to be associated with ACEi-associated cough in a dose-response manner; however, this was not seen in ACEI-associated angiodema. Overall, ACEi discontinuation was found to be correlated genetically with cough causes, which include gastro-esophageal reflux disease, allergic rhinitis, and asthma among others; all these indicate partly shared genetic underpinning between these traits.
Overall, the study reports a strong association between ADR phenotype and ACEi-associated cough.
Link to the article: https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehac322/6617745
References Ghouse, J., Tragante, V., Muhammad, A., Ahlberg, G., Skov, M. W., Roden, D. M., Jonsdottir, I., Andreasen, L., Lundegaard, P. R., Trudsø, L. C., Banasik, K., Brunak, S., Ostrowski, S. R., eMERGE consortium, Torp-Pedersen, C., Pedersen, O. V., Sørensen, E., Køber, L., Iversen, K., … Olesen, M. S. (2022). Polygenic risk score for ACE-inhibitor-associated cough based on the discovery of new genetic loci. European Heart Journal, ehac322. https://doi.org/10.1093/eurheartj/ehac322
