Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample
Abstract Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could improve our current understanding of pharmacogenetics from selected study populations. We provide real-world pharmacogeneti...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-05-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-021-01417-4 |
| _version_ | 1819101222057017344 |
|---|---|
| author | Carin A. T. C. Lunenburg Janne P. Thirstrup Jonas Bybjerg-Grauholm Marie Bækvad-Hansen David M. Hougaard Merete Nordentoft Thomas Werge Anders D. Børglum Ole Mors Preben B. Mortensen Christiane Gasse |
| author_facet | Carin A. T. C. Lunenburg Janne P. Thirstrup Jonas Bybjerg-Grauholm Marie Bækvad-Hansen David M. Hougaard Merete Nordentoft Thomas Werge Anders D. Børglum Ole Mors Preben B. Mortensen Christiane Gasse |
| author_sort | Carin A. T. C. Lunenburg |
| collection | DOAJ |
| description | Abstract Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could improve our current understanding of pharmacogenetics from selected study populations. We provide real-world pharmacogenetic frequencies of genotypes and (combined) phenotypes of a large Danish population-based case-cohort sample (iPSYCH2012; data of the Integrative Psychiatric Research consortium). The genotyped sample consists of 77,684 individuals, of which 51,464 individuals had diagnoses of severe mental disorders (SMD case-cohort) and 26,220 were individuals randomly selected from the Danish population (population cohort). Array-based genotype data imputed to 8.4 million genetic variants was searched for a selected pharmacogenetic panel of 42 clinically relevant variants and a CYP2D6 gene deletion and duplication. We identified 19 of 42 variants. Minor allele frequencies (MAFs) were consistent with previously reported MAFs, and did not differ between SMD cases and population cohorts. Almost all individuals carried at least one genetic variant (> 99.9%) and 87% carried three or more genetic variants. When genotypes were translated into phenotypes, also > 99.9% of individuals had at least one divergent phenotype (i.e. divergent from the common phenotypes considered normal, e.g. extensive metabolizer). The high number of identified individuals with at least one pharmacogenetic variant or divergent phenotype indicates the importance of pharmacogenetic panel-based genotyping. Combined CYP2C19-CYP2D6 phenotypes revealed that 72.7% of individuals had divergent phenotypes for one or both enzymes. As CYP2D6 and CYP2C19 have an important role in the metabolism of psychotropic drugs, this indicates the relevance of pharmacogenetic testing specifically in individuals using psychotropic drugs. |
| first_indexed | 2024-12-22T01:15:14Z |
| format | Article |
| id | doaj.art-01cd6bfe787a44a2b90f0fa9e1272506 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-22T01:15:14Z |
| publishDate | 2021-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-01cd6bfe787a44a2b90f0fa9e12725062022-12-21T18:43:53ZengNature Publishing GroupTranslational Psychiatry2158-31882021-05-011111910.1038/s41398-021-01417-4Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sampleCarin A. T. C. Lunenburg0Janne P. Thirstrup1Jonas Bybjerg-Grauholm2Marie Bækvad-Hansen3David M. Hougaard4Merete Nordentoft5Thomas Werge6Anders D. Børglum7Ole Mors8Preben B. Mortensen9Christiane Gasse10Department of Affective Disorders, Aarhus University Hospital PsychiatryDepartment of Biomedicine, Faculty of Health, Aarhus UniversityThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHDanish Center for Neonatal Screening, Statens Serum InstitutThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHDepartment of Biomedicine, Faculty of Health, Aarhus UniversityThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCHDepartment of Affective Disorders, Aarhus University Hospital PsychiatryAbstract Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could improve our current understanding of pharmacogenetics from selected study populations. We provide real-world pharmacogenetic frequencies of genotypes and (combined) phenotypes of a large Danish population-based case-cohort sample (iPSYCH2012; data of the Integrative Psychiatric Research consortium). The genotyped sample consists of 77,684 individuals, of which 51,464 individuals had diagnoses of severe mental disorders (SMD case-cohort) and 26,220 were individuals randomly selected from the Danish population (population cohort). Array-based genotype data imputed to 8.4 million genetic variants was searched for a selected pharmacogenetic panel of 42 clinically relevant variants and a CYP2D6 gene deletion and duplication. We identified 19 of 42 variants. Minor allele frequencies (MAFs) were consistent with previously reported MAFs, and did not differ between SMD cases and population cohorts. Almost all individuals carried at least one genetic variant (> 99.9%) and 87% carried three or more genetic variants. When genotypes were translated into phenotypes, also > 99.9% of individuals had at least one divergent phenotype (i.e. divergent from the common phenotypes considered normal, e.g. extensive metabolizer). The high number of identified individuals with at least one pharmacogenetic variant or divergent phenotype indicates the importance of pharmacogenetic panel-based genotyping. Combined CYP2C19-CYP2D6 phenotypes revealed that 72.7% of individuals had divergent phenotypes for one or both enzymes. As CYP2D6 and CYP2C19 have an important role in the metabolism of psychotropic drugs, this indicates the relevance of pharmacogenetic testing specifically in individuals using psychotropic drugs.https://doi.org/10.1038/s41398-021-01417-4 |
| spellingShingle | Carin A. T. C. Lunenburg Janne P. Thirstrup Jonas Bybjerg-Grauholm Marie Bækvad-Hansen David M. Hougaard Merete Nordentoft Thomas Werge Anders D. Børglum Ole Mors Preben B. Mortensen Christiane Gasse Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample Translational Psychiatry |
| title | Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample |
| title_full | Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample |
| title_fullStr | Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample |
| title_full_unstemmed | Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample |
| title_short | Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample |
| title_sort | pharmacogenetic genotype and phenotype frequencies in a large danish population based case cohort sample |
| url | https://doi.org/10.1038/s41398-021-01417-4 |
| work_keys_str_mv | AT carinatclunenburg pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT jannepthirstrup pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT jonasbybjerggrauholm pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT mariebækvadhansen pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT davidmhougaard pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT meretenordentoft pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT thomaswerge pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT andersdbørglum pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT olemors pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT prebenbmortensen pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample AT christianegasse pharmacogeneticgenotypeandphenotypefrequenciesinalargedanishpopulationbasedcasecohortsample |