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Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder |
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| Author: | Häkkinen, Katja1,2; Kiiski, Johanna I.3,4; Lähteenvuo, Markku1,2; |
| Organizations: |
1Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, FI-70240, Kuopio, Finland 2Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland 3Department of Clinical Pharmacology, University of Helsinki, FI-00014, Helsinki, Finland
4Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland View author publications
5Department of Psychiatry, University of Oulu, FI-90014, Oulu, Finland 6Tampere University, FI-33014, Tampere, Finland 7Social Services and Health Care Sector, City of Helsinki, FI-00099, Helsinki, Finland 8University of Helsinki, Helsinki University Hospital, Psychiatry, FI-00029, Helsinki, Finland 9Mental Health Unit, Finnish Institute for Health and Welfare, Helsinki, FI-00271, Finland 10Department of Psychiatry, University of Turku and Turku University Hospital, FI-20521, Turku, Finland 11Mehiläinen, FI-00260, Helsinki, Finland 12Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland 13Department of Psychiatry, Pirkanmaa Hospital District, FI-33521, Tampere, Finland 14Department of Psychiatry, Oulu University Hospital, FI-90220, Oulu, Finland 15Department of Psychiatry, University of Helsinki, FI-00014, Helsinki, Finland 16Pain Clinic, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, FI-00290, Helsinki, Finland 17Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland 18Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, FI-00029, Helsinki, Finland 19Department of Clinical Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden 20Center for Psychiatry Research, Stockholm City Council, SE-11364, Stockholm, Sweden 21Stanley Center for Psychiatric Research, The Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, MA-02142, Cambridge, MA, USA 22Analytical and Translational Genetics Unit, Massachusetts General Hospital, MA-02114, Boston, MA, USA |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 0.8 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2022102162729 |
| Language: | English |
| Published: |
Springer Nature,
2022
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| Publish Date: | 2022-10-21 |
| Description: |
AbstractWe demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data. see all
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| Series: |
Pharmacogenomics journal |
| ISSN: | 1470-269X |
| ISSN-E: | 1473-1150 |
| ISSN-L: | 1470-269X |
| Volume: | 22 |
| Issue: | 3 |
| Pages: | 166 - 172 |
| DOI: | 10.1038/s41397-022-00270-y |
| OADOI: | https://oadoi.org/10.1038/s41397-022-00270-y |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3111 Biomedicine 3124 Neurology and psychiatry |
| Subjects: | |
| Funding: |
The SUPER-Finland sample collection was funded by The Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, Boston, USA. KH has received funding from The Ministry of Social Affairs and Health Finland, through the developmental fund for Niuvanniemi Hospital, Kuopio, Finland, The Finnish Cultural Foundation, Helsinki, Finland, The Finnish Foundation for Psychiatric Research, Helsinki, Finland, The Social Insurance Institution of Finland, Helsinki, Finland and The Emil Aaltonen Foundation, Tampere, Finland. ML has received funding from The Finnish Medical Foundation, Helsinki, Finland and Emil Aaltonen Foundation, Tampere, Finland. KS has received funding from The Jalmari and Rauha Ahokas Foundation, Helsinki, Finland and The Finnish Foundation for Psychiatric Research, Helsinki, Finland. MN has received funding from Sigrid Jusélius Foundation, Helsinki, Finland. AVA has received funding from The Orion Research Foundation, Espoo, Finland, The Juho Vainio Foundation, Helsinki, Finland and The Finnish Post Doc Pool. Open access funding was provided by University of Eastern Finland (UEF) including Kuopio University Hospital. |
| Dataset Reference: |
The online version contains supplementary material available at https://doi.org/10.1038/s41397-022-00270-y. |
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https://doi.org/10.1038/s41397-022-00270-y |
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| Copyright information: |
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
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https://creativecommons.org/licenses/by/4.0/ |