Annual Scientific Meeting of the Pharmacogenomics Global Research Network (PGRN) June 12-13, 2023 Memphis, TN, USA

The 2023 Pharmacogenomics Global Research Network (PGRN) Annual Scientific Meeting took place June 12-13 at St. Jude Children’s Research Hospital in Memphis, Tennessee. The theme of the meeting, “Pushing Boundaries in Pharmacogenomics Discovery and Implementation”, captured the essence of the organization’s mission to “catalyze and lead research in precision medicine for the discovery and translation of genomic variation influencing therapeutic and adverse drug effects.” With a focus on both research and implementation in the global pharmacogenomics (PGx) community, the PGRN is at the forefront of the field. The 2023 Annual Scientific Meeting showcased the efforts of its members and collaborators which include researchers, clinicians and trainees from diverse scientific and clinical disciplines across the globe. Day 1 of the meeting consisted of scientific talks on both discovery science and clinical implementation and was divided into four sessions: Session 1, “Revolutionizing Precision Medicine with Advanced Genomic Analysis and Data Science,” explored the transformative potential of sophisticated genomic analysis techniques, unveiling new avenues for precision medicine advancements. In Session 2, “Innovative Technologies for Functional Genomics and Single-Cell Sequencing,” delved into the forefront of genomic research, evaluating cellular and genetic interactions through state-of-the-art single-cell sequencing technologies. Session 3, “Transformative New Models for Understanding the Interplay of Genetics and Drug Response,” brought to light groundbreaking models that offer novel insights into the intricate relationship between genetics and drug responses, fueling advancements in personalized medicine. Lastly, Session 4, “Overcoming Barriers to Pharmacogenomic and Genomic Medicine Implementation,” addressed the critical challenges hindering the integration of pharmacogenomic discoveries into clinical practice, catalyzing progress towards widespread implementation. After these sessions, the scientific discourse continued during a poster session, fostering dynamic discussions and collaborations among attendees. The meeting wrapped up with a half-day of workshops on the All of Us Research Program Researcher Workbench, PharmVar (http://www.pharmvar.org), PharmGKB (http://www.pharmgkb.org) and PharmCAT (http://pharmcat.org). Additionally, there were Special Interest Group (SIG) meetings for Oncology and Psychiatry. Together, these provided a unique opportunity for participants to learn how to leverage these critical platforms toward their pharmacogenomics research. In addition to the scientific programming, the 2023 PGRN Annual Scientific Meeting provided the PGx community an excellent opportunity to gather in person, cultivating lasting professional relationships and stimulating critical discussions to advance the field. As the PGx field continues to strengthen and expand, we envision the PGRN continuing to represent and promote the field around the globe, with the Annual Scientific Meeting as a connection point. Michelle Whirl-Carrillo, Akinyemi Oni-Orisan, Kristine R. Crews, Folefac Amienking – PGRN Publications Committee Marisa Medina and Erica Woodahl – PGRN Scientific Committee Jun Yang PGRN – PGRN President 1744-6872 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.DOI: 10.1097/FPC.0000000000000507 Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants Chad A. Bousman1,2,3*, James M. Stevenson4*, Laura B. Ramsey5,6, Katrin Sangkuhl7, J. Kevin Hicks8, Jeffrey R. Strawn9,10, Ajeet B. Singh11, Gualberto Ruaño12,13, Daniel J. Mueller14,15, Evangelia Eirini Tsermpini16, Jacob T. Brown17, Gillian C. Bell18, J. Steven Leeder19,20, Andrea Gaedigk19,20, Stuart A. Scott21,22, Teri E. Klein7, Kelly E. Caudle23, Jeffrey R. Bishop24,25 *Shared first author 1Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, and Community Health Sciences, University of Calgary, Alberta, Canada 2Alberta Children’s Hospital Research Institute, University of Calgary, Alberta, Canada 3Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada 4Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA 5Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA 6Divisions of Clinical Pharmacology and Research in Patient Services, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA 7Department of Biomedical Data Science, Stanford University, Stanford, CA, USA 8Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA 9Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA10Divisions of Child & Adolescent Psychiatry and Clinical Pharmacology Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA11School of Medicine, IMPACT Institute, Deakin University, Australia 12Institute of Living at Hartford Hospital, Hartford, CT, USA13Department of Psychiatry, University of Connecticut School of Medicine, Hartford, CT, USA 14Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada 15Department of Psychiatry, University of Toronto, Ontario, Canada 16Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia 17Department of Pharmacy Practice & Pharmaceutical Sciences, University of Minnesota College of Pharmacy, Duluth, MN, USA 18Genome Medical, South San Francisco, CA, USA 19Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Research Institute (CMRI), Kansas City, MO, USA 20School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA 21Department of Pathology, Stanford University, Palo Alto, CA, USA 22Stanford Medicine Clinical Genomics Program, Stanford Medicine, Stanford, CA, USA 23Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA24Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN, USA 25Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA Background: Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (SNRIs; i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI-like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Unfortunately, less than 40% of patients achieve remission from first line therapies and it is common for patients to experience side effects and lack of response that result in many trials of different medications and doses to achieve an acceptable therapeutic outcome. Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin-2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. Methods: This guideline updates and expands the 2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. A structured literature review identified 1,379 articles that were reviewed with 318 meeting inclusion criteria. Quality assessment of individual studies and strength of evidence for major finding statements were determined by the guideline committee group. Major finding statements were translated into dosing recommendations stratified by gene-drug pairs with a corresponding classification of recommendation assigned for each (i.e., no recommendations for CYP2D6 to dosing of fluvoxamine, paroxetine, and for the of CYP2C19 genotypes are provided for citalopram, escitalopram, and for the of CYP2B6 and in with CYP2C19 are provided for A classification was assigned to fluoxetine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and vilazodone to recommendations are provided for serotonin reuptake inhibitor on HTR2A and SLC6A4 genotypes the evidence an is to clinical and at and of in antidepressant response is a The literature clinical of pharmacogenomic is which may lead to in how from clinical are to This guideline recommendations and the strength of evidence the of genetic to the dosing of serotonin reuptake inhibitor antidepressants, as as evaluating pairs that are at Pharmacogenomic with and J. T. B. M. R. M. T. E. A. USA South San Francisco, USA University, Stanford, USA Genomics Laboratory, Stanford Medicine, Palo Alto, USA Background: In to pharmacogenomic (PGx) for precision PGx and include of and that are in many PGx for PGx include and their include towards and result in that are to potentially and clinical sequencing for and for and is With sequencing is and for to precision medicine research Methods: an PGx for sequencing that genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) as as PGx genes and genes of to the PGx research The was by and were and for genes on the have to and is for of the of the we Genetic at a of on a the an of with a of was across with of and PharmCAT and were to with and of a and how and with may affect with from Data from are the a and for and of PGx for both research and implementation the impact of on for precision medicine of and Therapeutic Sciences, University of San Francisco, San Francisco, CA, USA of and Health, Biomedical Data Science, and Genetics, Stanford University, Stanford, CA, USA Institute, University of San Francisco, USA 1 is and in the to in the and response to drugs. in affect the and efficacy of and how we a to the impact of of on its and been for the effects of many on and is the first of to in a Methods: to a of and in a the impact of on and we to we a is with by of a the of in from and the impact of these on from in the and and excellent with of and was the primary of a impact on that of the and on the of common that in are with of and in from a identified a with and in for and for in on Cancer and R. of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minneapolis, MN, USA Background: The of been in and for the of the been in its potential to with and impact and we in the and how and drug the with different between and in different in The Cancer the that are unique and by different and the of The between and was The impact of on was in of and are to have the of and are to have the of than identified that are by is in in different of the are of clinical analysis that is in in in line with the finding that are to in than of the are to drug is to in in and the been to in including that is different between and in The identified in analysis may to the in and drug of for with B. Jude Children’s Research Hospital, of Memphis, TN, USA of Health Center, of Health and Memphis, TN, Jude Children’s Research Hospital, of Pathology, Memphis, TN, USA Jude Children’s Research Hospital, of Memphis, TN, USA Background: With including clinical and new are to these and of which profiles with clinical to a of genes on the of the each a of the and to analysis a of is of of profiles and to with a a with Methods: the of to analysis including the global the evidence and through global and to a with and genomic on patients from the Children’s Oncology Group clinical were with and In to the of with and to analysis In the identified genes as of these genes are with in the and of these genes were by that and may to patients at of finding was which was among the genes identified by been in is its in A in was with and of was with genes these with of is a and to genes for in clinical research. This was by St. Jude Children’s Research Hospital, and and of genetic variation on and side effects among with Chad A. of Medical Genetics, University of Calgary, Calgary, Canada Centre for Mental Health Research & Education, Hotchkiss Brain Institute, School of Medicine, University of Calgary, Calgary, of Psychiatry, University of Calgary, Calgary, Canada of Physiology & Pharmacology, University of Calgary, Calgary, Canada 5Department of Community Health Sciences, University of Calgary, Calgary, Canada Children’s Hospital Research Institute, University of Calgary, Calgary, Canada 7Department of Sciences, University of Calgary, Calgary, Canada Background: is a selective serotonin reuptake inhibitor that for the of major depressive and in and clinical trials have is to and it is as a in clinical up to of to and up to experience side in efficacy and in a result of in metabolism is and with CYP2D6 a major and its are inhibitors of This and lack of clinical of for a As we examined of were with and side effects among with in an of implementation in the and with a major depressive and a of were All participants provided a of and a The review drug and as as (i.e., to side effects and is for was from the and for CYP2D6, CYP2C19, and the and CYP2D6 variation models were to the impact of on and side CYP2D6 was with of – and side effects – for and of the with side effects were for the that as the CYP2D6 the of and side effects among and with these a in the for CYP2D6 may to side CYP2D6 may from an SSRI by CYP2D6 Global analysis of the A. of Biomedical for Medicine, University of Medical USA of Pharmacogenetics (PGx) how individual genetic impact drug and the potential to and there have been in of PGx and PGx variation is which studies have on of and to implementation of PGx it is to the inclusion of The of was to and for the 1000 global sequencing and genes that have a in drug and from sequencing by and With sequencing in drug have been to and in to among genes and a with the to including and that many of and were with the was to that at a This that may have these and identified novel that are in PGx in we identified and with of these have been identified as a that to clinical across diverse and Andrea of Molecular and Genetics, University of of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Research Institute (CMRI), Kansas City, USA Background: is to drug to individual are research and clinical implementation. The Consortium for which is across research and clinical implementation. The and genes which a of and been across and that genetic a for adverse drug is in the and Drug of pharmacogenomic Drug for and have for dosing on the Clinical Pharmacogenetics Implementation Consortium and for a Methods: are on the as it is by the University of in to it to been to and to the for The to the of the for the of the genomic of to with PharmVar and and of evidence In addition, a literature review and 1000 are to and captured by PharmVar as a new the from the to to a include and as their to unique of the to new to with PharmVar Lastly, at new were in the 1000 The of to PharmVar is for efforts for The of to PharmVar is a for the of of the PharmVar with PharmGKB and for clinical guideline as as a to research at In addition, the and platforms and to and genotypes from which is for clinical and A in the for with and J. of Pharmacology & University of Toronto, Toronto, Canada Family Mental Health Research Institute, Toronto, Canada of Psychiatry, University of Toronto, Toronto, Canada Cancer Center, University of USA Institute, University Medical School, Background: is an in and the metabolism of in the and the for a genetic which and clinical This to between variation and in the Methods: The was genotypes from the for each of the in the a in The consisted of & as between the and were in models for the and an clinical were to the effects of variation on the models and were to as at of between and The identified between and the and as the with with by a of of in to to The were the and we as in the and and in were among a between and the in that metabolism was with at of for the among This evidence that metabolism is with an of and among that metabolism to an the of genetic and in and Pharmacogenomic in the of the Minnesota of Pharmacogenomic Jeffrey R. of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minneapolis, USA of and Medicine, Hospital, University, of of Pharmacy, St. USA of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minneapolis, USA 5Department of Pharmaceutical and Health College of Pharmacy, University of Minneapolis, USA of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minneapolis, of Psychiatry, University of Minnesota Medical School, Minneapolis, USA Background: The Minnesota of Pharmacogenomic was by as the first to pharmacogenomic (PGx) in clinical and research four primary PGx and identified as for to As of an to the and of the we translated and the into which is by of the global the of the and it to PGx in a of Methods: The was by from to translation the and PGx among the an was that and the All of Health and the a of the to of were to that the and of the were of through a of and through platforms from to The of the on the were determined by and to individual and were examined in with participants and After assessment of from were in the All were in with identified as The were in and were in to the of the with the with were and in the of participants on the was by a and of of PGx in PGx on the was with and of PGx was by of of medications in the PGx was with and experience with genetic The was a of and The properties with the and and that it to a to PGx in clinical pharmacogenomic sequencing Jeffrey R. of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minneapolis, MN, USA of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minneapolis, MN, of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA of Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA Background: Pharmacogenomic (PGx) and clinical is into clinical and by Clinical PGx sequencing for an individual a of genes of potential clinical and clinical sequencing include PGx and PGx been in the of to a to PGx as of the clinical and how impact clinical Methods: The for PGx at Health was PGx and to in the CYP2D6 and for the analysis of (i.e., CYP2B6, CYP2C19, and to translation in the Clinical Pharmacogenetics Implementation Consortium (CPIC) was on the of with diverse from the Genetic Program were by of the as as from the of sequencing translated to across genes for and therapeutic recommendations for medications on the by was on genes and on genes CYP2B6, and on The of CYP2D6 by was as to the The of unique from to participants than of with translated across with to the of the of medications was from to for antidepressants, to for for and for and PGx was to PGx from clinical of an diverse The and include PGx from at the clinical impact of PGx on the medications of each the was and of the implementation of clinical for patients and of to a Pharmacogenomics to in A. M. M. Health, University Medical Center, USA Background: Clinical a for trials for Clinical trials are and in PGx studies focus on participants with genetic The was to the and of to a among patients with in the Methods: participants to a with with were from primary The to by a the were A was for for PGx were no Data for and efforts were of primary to in the the patients were for and efforts to a to to patients 1, 1, were to and in of and by were to in the for patients with in patients in and to patients with and that were and patients patients potentially progress to were The common for were lack of a from a and The patients was were for each and to potential for patients and efforts were to for a to clinical of is of the effects of are is with Clinical in B. of and Research and for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of FL, USA of Sciences, College of Medicine, University of FL, of Jude Children’s Research Hospital, Memphis, TN, USA of Health Center, TN, of Jude Children’s Research Hospital, Memphis, TN, USA Background: and as the for the of new drugs. many patients in it is to the Methods: In we a to response modulators and with and clinical in with The was into and the was with of for four at After the of was with to for the of is as genes and as genes with in at of was for with clinical including and 1 in clinical with for for and for All and were with and and and are identified as genes and are genes to genes are for studies between and clinical 1 is a the genes with of the and clinical in with for the of potential drug and are identified as genes for and in in with The for that the of and inhibitor been for the of the potential for inhibitor to drug in is a that the between and and it was to in in with a potential drug in with to drug as research on the of these genes and the of on the of and are novel genes with a in patients have been with Precision through an Pharmacogenomics Program Jacob T. Jeffrey R. & of USA of USA Background: A of evidence that pharmacogenomic (PGx) in as and PGx have of patients have a PGx of and of were a with PGx Additionally, 40% of with interactions in were in the the for an PGx in Methods: analysis on of pharmacogenomic and implementation of an is and The was by the Children’s Minnesota include a review of the to the on and an PGx of and in at Children’s Minnesota review of PGx the of and the of clinical and their The was an and with from an and including and The patients with PGx and a PGx on medications and are as on an a of which are to the The on from the and and from the four of the include a to the four and an assessment of of and and of PGx and of PGx in the are during and of PGx implementation of a A of participants to the with a response of these inclusion of in the The of the were and the common were and critical by of were with PGx and were in their to PGx that PGx are with as A in to Michelle Folefac of University Cancer Institute of Medicine, School of Medicine, University of Institute of University of of Medical Cancer Medical School, University of of Pharmacy, University Hospital of Medicine, University Medicine University Health 8Department of Medicine, Hospital Program, and and University of and Research Center, University of and Institute of for Science, and Research School of Medicine, University of Molecular and of and Research of and Molecular Cancer Centre and Medical School, Cancer Centre of Education, Medical School, of University Medicine University Health of Biomedical School of Medicine, University of of Pharmacology, School of Medicine, University of of School of Medicine, University of to are of Background: is an with properties that been as a in the of a of including and Unfortunately, its as in of patients and is in are no treatments for as an in it is a first line for of the the of genetic and in patients and novel genetic In addition, we the of Methods: patients from the University Cancer Institute, was and by were Global was for of patients was different between and clinical were the of and novel and The was to the of and of of to with at the line the a in to with a effect in the of the that and were up in to the were with we that is in a with a for the of at the to C. The was to the of genes with effects on the and The that was at the the of was the with both and a This inhibitor drug the of by is in an and the cellular response to of a and the of the by and This insights into and potential new for to the that the of and in the Clinical to of of Pharmacology and University of Toronto, Toronto, Canada Family Mental Health Research Institute, Centre for Addiction and Mental Health Toronto, of Psychiatry, University of Toronto, Toronto, Toronto, Canada Centre Canada 5Department of Psychiatry and Faculty of Medicine, Centre on Canada 7Department of Family Faculty of Medicine, University of of Medicine, Faculty of Medicine, University of Canada School of Health, University of Toronto, Toronto, Canada Addiction Research Laboratory, Campbell Family Mental Health Research Institute, for Addiction and Mental Health Toronto, Canada of Family and Community Medicine, Toronto, Ontario, Canada Centre for Addiction and Mental Health, Toronto, Ontario, Canada Research Institute, Centre for Mental Health Ontario, Canada Background: is a major in Canada and the and are therapies for genetic are to to individual in studies have variation to clinical in patients and Understanding influences on genes to the and of and may of

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