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

<p dir="ltr">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 ph...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Dinesh Velayutham (5444072) (author)
مؤلفون آخرون: Kholoud Bastaki (18434094) (author), Areeba Irfan (19255795) (author), Mohammed Abuhaliqa (18434091) (author), Aisha AlMulla (22466677) (author), the Qatar Genome Program Research Consortium (22466680) (author), Suhaila Ghuloum (796180) (author), Muhammad Waqar Azeem (11909633) (author), Munir Pirmohamed (40546) (author), Puthen Veettil Jithesh (12040358) (author)
منشور في: 2025
الموضوعات:
الوسوم: إضافة وسم
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author Dinesh Velayutham (5444072)
author2 Kholoud Bastaki (18434094)
Areeba Irfan (19255795)
Mohammed Abuhaliqa (18434091)
Aisha AlMulla (22466677)
the Qatar Genome Program Research Consortium (22466680)
Suhaila Ghuloum (796180)
Muhammad Waqar Azeem (11909633)
Munir Pirmohamed (40546)
Puthen Veettil Jithesh (12040358)
author2_role author
author
author
author
author
author
author
author
author
author_facet Dinesh Velayutham (5444072)
Kholoud Bastaki (18434094)
Areeba Irfan (19255795)
Mohammed Abuhaliqa (18434091)
Aisha AlMulla (22466677)
the Qatar Genome Program Research Consortium (22466680)
Suhaila Ghuloum (796180)
Muhammad Waqar Azeem (11909633)
Munir Pirmohamed (40546)
Puthen Veettil Jithesh (12040358)
author_role author
dc.creator.none.fl_str_mv Dinesh Velayutham (5444072)
Kholoud Bastaki (18434094)
Areeba Irfan (19255795)
Mohammed Abuhaliqa (18434091)
Aisha AlMulla (22466677)
the Qatar Genome Program Research Consortium (22466680)
Suhaila Ghuloum (796180)
Muhammad Waqar Azeem (11909633)
Munir Pirmohamed (40546)
Puthen Veettil Jithesh (12040358)
dc.date.none.fl_str_mv 2025-04-01T00:00:00Z
dc.identifier.none.fl_str_mv 10.1017/pcm.2025.2
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Clinically_actionable_pharmacogenomic_landscape_of_antidepressants_and_antipsychotics_in_Qatar_a_population-based_cohort_study/30405586
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
Precision medicine
Pharmacogenomics
Psychotropics
Whole genome sequencing
Clinical implementation
dc.title.none.fl_str_mv Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">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 (<i>CYP2C19, CYP2D6, CYP2B6 </i>and<i> CYP3A4</i>). 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 <i>CYP3A4 </i>and<i> CYP2D6</i>. 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 along with population-specific variants will help in the pharmacogenomics implementation in the Qatari population.</p><h2>Other Information</h2><p dir="ltr">Published in: Cambridge Prisms: Precision Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1017/pcm.2025.2" target="_blank">https://dx.doi.org/10.1017/pcm.2025.2</a></p>
eu_rights_str_mv openAccess
id Manara2_9731c336e5f1f6b1b5ff0083416c90d7
identifier_str_mv 10.1017/pcm.2025.2
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/30405586
publishDate 2025
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spelling Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort studyDinesh Velayutham (5444072)Kholoud Bastaki (18434094)Areeba Irfan (19255795)Mohammed Abuhaliqa (18434091)Aisha AlMulla (22466677)the Qatar Genome Program Research Consortium (22466680)Suhaila Ghuloum (796180)Muhammad Waqar Azeem (11909633)Munir Pirmohamed (40546)Puthen Veettil Jithesh (12040358)Biological sciencesGeneticsBiomedical and clinical sciencesPharmacology and pharmaceutical sciencesPrecision medicinePharmacogenomicsPsychotropicsWhole genome sequencingClinical implementation<p dir="ltr">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 (<i>CYP2C19, CYP2D6, CYP2B6 </i>and<i> CYP3A4</i>). 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 <i>CYP3A4 </i>and<i> CYP2D6</i>. 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 along with population-specific variants will help in the pharmacogenomics implementation in the Qatari population.</p><h2>Other Information</h2><p dir="ltr">Published in: Cambridge Prisms: Precision Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1017/pcm.2025.2" target="_blank">https://dx.doi.org/10.1017/pcm.2025.2</a></p>2025-04-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1017/pcm.2025.2https://figshare.com/articles/journal_contribution/Clinically_actionable_pharmacogenomic_landscape_of_antidepressants_and_antipsychotics_in_Qatar_a_population-based_cohort_study/30405586CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/304055862025-04-01T00:00:00Z
spellingShingle Clinically actionable pharmacogenomic landscape of antidepressants and antipsychotics in Qatar: a population-based cohort study
Dinesh Velayutham (5444072)
Biological sciences
Genetics
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
Precision medicine
Pharmacogenomics
Psychotropics
Whole genome sequencing
Clinical implementation
status_str publishedVersion
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 Biological sciences
Genetics
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
Precision medicine
Pharmacogenomics
Psychotropics
Whole genome sequencing
Clinical implementation