Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study

Consortia like the Clinical Pharmacogenetic Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG) provide clinical guidelines but pharmacogenomics implementation depends on population prevalence of actionable genetic variants and response phenotypes. We analyzed the dis...

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Main Authors: Dinesh Velayutham, Kholoud Bastaki, Areeba Irfan, Mohammed Abuhaliqa, Aisha AlMulla, the Qatar Genome Program Research Consortium, Suhaila Ghuloum, Muhammad Waqar Azeem, Munir Pirmohamed, Puthen Veettil Jithesh
Format: Article
Language:English
Published: Cambridge University Press 2025-01-01
Series:Cambridge Prisms: Precision Medicine
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Online Access:https://www.cambridge.org/core/product/identifier/S275261432500002X/type/journal_article
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author Dinesh Velayutham
Kholoud Bastaki
Areeba Irfan
Mohammed Abuhaliqa
Aisha AlMulla
the Qatar Genome Program Research Consortium
Suhaila Ghuloum
Muhammad Waqar Azeem
Munir Pirmohamed
Puthen Veettil Jithesh
author_facet Dinesh Velayutham
Kholoud Bastaki
Areeba Irfan
Mohammed Abuhaliqa
Aisha AlMulla
the Qatar Genome Program Research Consortium
Suhaila Ghuloum
Muhammad Waqar Azeem
Munir Pirmohamed
Puthen Veettil Jithesh
author_sort Dinesh Velayutham
collection DOAJ
description Consortia like the Clinical Pharmacogenetic Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG) provide clinical guidelines but pharmacogenomics implementation depends on population prevalence of actionable genetic variants and response phenotypes. We analyzed the distribution of actionable genetic variants and clinical recommendations in 14,354 adult Qataris, focusing only genes with guidelines (CYP2C19, CYP2D6, CYP2B6 and CYP3A4). Haplotypes and diplotypes were generated from 490 alleles using whole genome data and metabolizer phenotypes were predicted based on current knowledge. Qatari population predicted to have actionable metabolizer phenotypes of CYP2C19, CYP2B6 and CYP2D6 impacting response to antidepressants were in the range of 1%–58% and for antipsychotics 0.1%–33% based on CYP3A4 and CYP2D6. Fine-grained analysis based on clinical guidelines also revealed that while the Qataris may need prescription of an alternate antidepressant not metabolized by CYP2C19, patients from other populations may just need altering the dosage of tricyclic antidepressants like amitriptyline. Further studies incorporating other factors such as diet, environment and cultural habits alongwith population-specific variants will help in the pharmacogenomics implementation in the Qatari population.
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series Cambridge Prisms: Precision Medicine
spelling doaj-art-9df48d5c1b2b41daa7e6fc1886ef835b2025-08-20T03:27:21ZengCambridge University PressCambridge Prisms: Precision Medicine2752-61432025-01-01310.1017/pcm.2025.2Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort studyDinesh Velayutham0Kholoud Bastaki1Areeba Irfan2Mohammed Abuhaliqa3Aisha AlMulla4the Qatar Genome Program Research ConsortiumSuhaila Ghuloum5Muhammad Waqar Azeem6Munir Pirmohamed7Puthen Veettil Jithesh8https://orcid.org/0000-0001-7747-0930College of Health & Life Sciences, Hamad Bin Khalifa University, Doha, QatarCollege of Pharmacy, QU Health, Qatar University, Doha, QatarCollege of Health & Life Sciences, Hamad Bin Khalifa University, Doha, QatarResearch Department, Sidra Medicine, Doha, QatarCollege of Health & Life Sciences, Hamad Bin Khalifa University, Doha, QatarDepartment of Psychiatry, Hamad Medical Corporation, Doha, QatarDepartment of Psychiatry, Sidra Medicine, Doha, QatarPharmacology & Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UKCollege of Health & Life Sciences, Hamad Bin Khalifa University, Doha, Qatar Pharmacology & Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UKConsortia like the Clinical Pharmacogenetic Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG) provide clinical guidelines but pharmacogenomics implementation depends on population prevalence of actionable genetic variants and response phenotypes. We analyzed the distribution of actionable genetic variants and clinical recommendations in 14,354 adult Qataris, focusing only genes with guidelines (CYP2C19, CYP2D6, CYP2B6 and CYP3A4). Haplotypes and diplotypes were generated from 490 alleles using whole genome data and metabolizer phenotypes were predicted based on current knowledge. Qatari population predicted to have actionable metabolizer phenotypes of CYP2C19, CYP2B6 and CYP2D6 impacting response to antidepressants were in the range of 1%–58% and for antipsychotics 0.1%–33% based on CYP3A4 and CYP2D6. Fine-grained analysis based on clinical guidelines also revealed that while the Qataris may need prescription of an alternate antidepressant not metabolized by CYP2C19, patients from other populations may just need altering the dosage of tricyclic antidepressants like amitriptyline. Further studies incorporating other factors such as diet, environment and cultural habits alongwith population-specific variants will help in the pharmacogenomics implementation in the Qatari population.https://www.cambridge.org/core/product/identifier/S275261432500002X/type/journal_articlePrecision medicinePharmacogenomicsPsychotropicsWhole genome sequencingClinical implementation
spellingShingle Dinesh Velayutham
Kholoud Bastaki
Areeba Irfan
Mohammed Abuhaliqa
Aisha AlMulla
the Qatar Genome Program Research Consortium
Suhaila Ghuloum
Muhammad Waqar Azeem
Munir Pirmohamed
Puthen Veettil Jithesh
Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
Cambridge Prisms: Precision Medicine
Precision medicine
Pharmacogenomics
Psychotropics
Whole genome sequencing
Clinical implementation
title Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
title_full Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
title_fullStr Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
title_full_unstemmed Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
title_short Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
title_sort clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in qatar a population based cohort study
topic Precision medicine
Pharmacogenomics
Psychotropics
Whole genome sequencing
Clinical implementation
url https://www.cambridge.org/core/product/identifier/S275261432500002X/type/journal_article
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