Evaluation of population‐level pharmacogenetic actionability in Alabama

Abstract The evolution of evidence and availability of Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines have enabled assessment of pharmacogenetic (PGx) actionability and clinical implementation. However, population‐level actionability is not well‐characterized. We leveraged the...

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Autores principales:	Brittney H. Davis, Kelly Williams, Devin Absher, Bruce Korf, Nita A. Limdi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/d2f206528b0f46e5aa0f3e0e2001aa3f
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spelling	oai:doaj.org-article:d2f206528b0f46e5aa0f3e0e2001aa3f2021-11-19T17:51:35ZEvaluation of population‐level pharmacogenetic actionability in Alabama1752-80621752-805410.1111/cts.13097https://doaj.org/article/d2f206528b0f46e5aa0f3e0e2001aa3f2021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13097https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract The evolution of evidence and availability of Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines have enabled assessment of pharmacogenetic (PGx) actionability and clinical implementation. However, population‐level actionability is not well‐characterized. We leveraged the Alabama Genomic Health Initiative (AGHI) to evaluate population‐level PGx actionability. Participants (>18 years), representing all 67 Alabama counties, were genotyped using the Illumina Global Screening array. Using CPIC guidelines, actionability was evaluated using (1) genotype data and genetic ancestry, (2) prescribing data, and (3) combined genotype and medication data. Of 6,331 participants, 4230 had genotype data and 3386 had genotype and prescription data (76% women; 76% White/18% Black [self‐reported]). Genetic ancestry was concordant with self‐reported race. For CPIC level A genes, 98.6% had an actionable genotype (99.4% Blacks/African; 98.5% White/European). With the exception of DPYD and CYP2C19, the prevalence of actionable genotypes by gene differed significantly by race. Based on prescribing, actionability was highest for CYP2D6 (70.9%), G6PD (54.1%), CYP2C19 (53.5%), and CYP2C9 (47.5%). Among participants prescribed atenolol, carvedilol, or metoprolol, ~ 50% had an actionable ADRB1 genotype, associated with decreased therapeutic response, with higher actionability among Blacks compared to Whites (62.5% vs. 47.4%; p < 0.0001). Based on both genotype and prescribing frequencies, no significant differences in actionability were observed between men and women. This statewide effort highlights PGx population‐level impact to help optimize pharmacotherapy. Almost all Alabamians harbor an actionable genotype, and a significant proportion are prescribed affected medications. Statewide efforts, such as AGHI, lay the foundation for translational research and evaluate “real‐world” outcomes of PGx.Brittney H. DavisKelly WilliamsDevin AbsherBruce KorfNita A. LimdiWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2327-2338 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Brittney H. Davis Kelly Williams Devin Absher Bruce Korf Nita A. Limdi Evaluation of population‐level pharmacogenetic actionability in Alabama
description	Abstract The evolution of evidence and availability of Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines have enabled assessment of pharmacogenetic (PGx) actionability and clinical implementation. However, population‐level actionability is not well‐characterized. We leveraged the Alabama Genomic Health Initiative (AGHI) to evaluate population‐level PGx actionability. Participants (>18 years), representing all 67 Alabama counties, were genotyped using the Illumina Global Screening array. Using CPIC guidelines, actionability was evaluated using (1) genotype data and genetic ancestry, (2) prescribing data, and (3) combined genotype and medication data. Of 6,331 participants, 4230 had genotype data and 3386 had genotype and prescription data (76% women; 76% White/18% Black [self‐reported]). Genetic ancestry was concordant with self‐reported race. For CPIC level A genes, 98.6% had an actionable genotype (99.4% Blacks/African; 98.5% White/European). With the exception of DPYD and CYP2C19, the prevalence of actionable genotypes by gene differed significantly by race. Based on prescribing, actionability was highest for CYP2D6 (70.9%), G6PD (54.1%), CYP2C19 (53.5%), and CYP2C9 (47.5%). Among participants prescribed atenolol, carvedilol, or metoprolol, ~ 50% had an actionable ADRB1 genotype, associated with decreased therapeutic response, with higher actionability among Blacks compared to Whites (62.5% vs. 47.4%; p < 0.0001). Based on both genotype and prescribing frequencies, no significant differences in actionability were observed between men and women. This statewide effort highlights PGx population‐level impact to help optimize pharmacotherapy. Almost all Alabamians harbor an actionable genotype, and a significant proportion are prescribed affected medications. Statewide efforts, such as AGHI, lay the foundation for translational research and evaluate “real‐world” outcomes of PGx.
format	article
author	Brittney H. Davis Kelly Williams Devin Absher Bruce Korf Nita A. Limdi
author_facet	Brittney H. Davis Kelly Williams Devin Absher Bruce Korf Nita A. Limdi
author_sort	Brittney H. Davis
title	Evaluation of population‐level pharmacogenetic actionability in Alabama
title_short	Evaluation of population‐level pharmacogenetic actionability in Alabama
title_full	Evaluation of population‐level pharmacogenetic actionability in Alabama
title_fullStr	Evaluation of population‐level pharmacogenetic actionability in Alabama
title_full_unstemmed	Evaluation of population‐level pharmacogenetic actionability in Alabama
title_sort	evaluation of population‐level pharmacogenetic actionability in alabama
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/d2f206528b0f46e5aa0f3e0e2001aa3f
work_keys_str_mv	AT brittneyhdavis evaluationofpopulationlevelpharmacogeneticactionabilityinalabama AT kellywilliams evaluationofpopulationlevelpharmacogeneticactionabilityinalabama AT devinabsher evaluationofpopulationlevelpharmacogeneticactionabilityinalabama AT brucekorf evaluationofpopulationlevelpharmacogeneticactionabilityinalabama AT nitaalimdi evaluationofpopulationlevelpharmacogeneticactionabilityinalabama
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Evaluation of population‐level pharmacogenetic actionability in Alabama

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