Integrating CRISPR functional genomics with admixture-aware psychotropic pharmacogenetics in Brazil

Area of Science:

• Psychiatry
• Genomics
• Pharmacology

Background:

• Clinical response to psychotropic medications varies significantly, impacting psychiatric care effectiveness.
• Pharmacogenetics offers personalized therapy but faces challenges in genetically diverse populations like Brazil due to extensive admixture.
• Existing international pharmacogenetic guidelines have limited applicability in Brazil's heterogeneous genomic landscape.

Purpose of the Study:

• To review ancestry-dependent allele frequencies and genetic gradients in Brazil.
• To discuss the clinical implications of genetic diversity for psychotropic prescribing.
• To explore integrating CRISPR functional genomics with admixture-aware psychiatry for personalized medicine.

Main Methods:

• Synthesizing evidence on allele frequencies and genetic gradients in Brazil.
• Reviewing the clinical implications for psychotropic drug prescribing.
• Discussing the integration of CRISPR functional genomics and admixture-aware psychiatry.

Main Results:

• Brazil's genetic heterogeneity, resulting from European, African, and Indigenous admixture, complicates direct application of global pharmacogenetic guidelines.
• Population-specific variants can be validated, metabolizer phenotypes refined, and ancestry-informed guidelines developed using integrated approaches.
• Combining genome editing, pharmacogenomic profiling, and admixture data can enhance dose prediction and minimize adverse drug reactions.

Conclusions:

• An integrative approach combining pharmacogenetics, functional genomics, and precision medicine is crucial for equitable psychopharmacology.
• This strategy can improve psychotropic drug efficacy, reduce adverse events, and promote health equity in Brazil.
• Brazil can serve as a global model for developing ancestry-aware psychopharmacology practices.