RESUMO
Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.
RESUMO
BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.
