Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder

Katja Häkkinen^{1

2}, Johanna I Kiiski^{3

4}, Markku Lähteenvuo^{5

6}, Tuomas Jukuri^{6

7}, Kimmo Suokas^{6

8}, Jussi Niemi-Pynttäri^{6

9}, Tuula Kieseppä^{6

10

11}, Teemu Männynsalo^{6

9}, Asko Wegelius^{6

10

11}, Willehard Haaki^{6

12}, Kaisla Lahdensuo^{6

13}, Risto Kajanne⁶, Mari A Kaunisto⁶, Annamari Tuulio-Henriksson¹⁴, Olli Kampman^{8

15}, Jarmo Hietala¹², Juha Veijola^{7

16}, Jouko Lönnqvist^{11

17}, Erkki Isometsä¹⁰, Tiina Paunio^{10

11

17}, Jaana Suvisaari¹¹, Eija Kalso¹⁸, Mikko Niemi^{3

4

19}, Jari Tiihonen^{5

20

21}, Mark Daly^{6

22

23}, Aarno Palotie^{6

22

23}, Ari V Ahola-Olli^{6

22

23}

Affiliations

¹ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, FI-70240, Kuopio, Finland. katja.hakkinen@niuva.fi.
² Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland. katja.hakkinen@niuva.fi.
³ Department of Clinical Pharmacology, University of Helsinki, FI-00014, Helsinki, Finland.
⁴ Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland.
⁵ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, FI-70240, Kuopio, Finland.
⁶ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland.
⁷ Department of Psychiatry, University of Oulu, FI-90014, Oulu, Finland.
⁸ Tampere University, FI-33014, Tampere, Finland.
⁹ Social Services and Health Care Sector, City of Helsinki, FI-00099, Helsinki, Finland.
¹⁰ University of Helsinki, Helsinki University Hospital, Psychiatry, FI-00029, Helsinki, Finland.
¹¹ Mental Health Unit, Finnish Institute for Health and Welfare, Helsinki, FI-00271, Finland.
¹² Department of Psychiatry, University of Turku and Turku University Hospital, FI-20521, Turku, Finland.
¹³ Mehiläinen, FI-00260, Helsinki, Finland.
¹⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland.
¹⁵ Department of Psychiatry, Pirkanmaa Hospital District, FI-33521, Tampere, Finland.
¹⁶ Department of Psychiatry, Oulu University Hospital, FI-90220, Oulu, Finland.
¹⁷ Department of Psychiatry, University of Helsinki, FI-00014, Helsinki, Finland.
¹⁸ Pain Clinic, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, FI-00290, Helsinki, Finland.
¹⁹ Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, FI-00029, Helsinki, Finland.
²⁰ Department of Clinical Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden.
²¹ Center for Psychiatry Research, Stockholm City Council, SE-11364, Stockholm, Sweden.
²² Stanley Center for Psychiatric Research, The Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, MA-02142, Cambridge, MA, USA.
²³ Analytical and Translational Genetics Unit, Massachusetts General Hospital, MA-02114, Boston, MA, USA.

PMID: 35197553
PMCID: PMC9151384
DOI: 10.1038/s41397-022-00270-y

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder

Katja Häkkinen et al. Pharmacogenomics J. 2022 May.

. 2022 May;22(3):166-172.

doi: 10.1038/s41397-022-00270-y. Epub 2022 Feb 23.

Authors

Affiliations

¹ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, FI-70240, Kuopio, Finland. katja.hakkinen@niuva.fi.
² Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland. katja.hakkinen@niuva.fi.
³ Department of Clinical Pharmacology, University of Helsinki, FI-00014, Helsinki, Finland.
⁴ Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland.
⁵ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, FI-70240, Kuopio, Finland.
⁶ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, FI-00014, Helsinki, Finland.
⁷ Department of Psychiatry, University of Oulu, FI-90014, Oulu, Finland.
⁸ Tampere University, FI-33014, Tampere, Finland.
⁹ Social Services and Health Care Sector, City of Helsinki, FI-00099, Helsinki, Finland.
¹⁰ University of Helsinki, Helsinki University Hospital, Psychiatry, FI-00029, Helsinki, Finland.
¹¹ Mental Health Unit, Finnish Institute for Health and Welfare, Helsinki, FI-00271, Finland.
¹² Department of Psychiatry, University of Turku and Turku University Hospital, FI-20521, Turku, Finland.
¹³ Mehiläinen, FI-00260, Helsinki, Finland.
¹⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, FI-00014, Helsinki, Finland.
¹⁵ Department of Psychiatry, Pirkanmaa Hospital District, FI-33521, Tampere, Finland.
¹⁶ Department of Psychiatry, Oulu University Hospital, FI-90220, Oulu, Finland.
¹⁷ Department of Psychiatry, University of Helsinki, FI-00014, Helsinki, Finland.
¹⁸ Pain Clinic, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, FI-00290, Helsinki, Finland.
¹⁹ Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, FI-00029, Helsinki, Finland.
²⁰ Department of Clinical Neuroscience, Karolinska Institutet, SE-17177, Stockholm, Sweden.
²¹ Center for Psychiatry Research, Stockholm City Council, SE-11364, Stockholm, Sweden.
²² Stanley Center for Psychiatric Research, The Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, MA-02142, Cambridge, MA, USA.
²³ Analytical and Translational Genetics Unit, Massachusetts General Hospital, MA-02114, Boston, MA, USA.

PMID: 35197553
PMCID: PMC9151384
DOI: 10.1038/s41397-022-00270-y

Abstract

We 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.

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Conflict of interest statement

ML is a board member of Genomi Solutions ltd. and Nursie Health ltd., has received honoraria from Sunovion ltd., Orion Pharma ltd., Otsuka ltd. and Janssen-Cilag. Part of MK’s and RK’s salaries are covered by a large Finnish biobank study FinnGen, funded by twelve international pharmaceutical companies (Abbvie, AstraZeneca, Biogen, Celgene, Genentech, GSK, Janssen, Maze Therapeutics, Merck/MSD, Novartis, Pfizer and Sanofi) and Business Finland. JT has participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to his employing institution, has received honoraria from Eli Lilly, Janssen-Cilag, Lundbeck and Otsuka, and is a member of advisory board for Lundbeck. AVA is an employee and shareholder of Abomics, a company providing pharmacogenetic consultation services. The other authors declare no conflict of interest.

Figures

**Fig. 1**
A flow chart of study protocol.

See this image and copyright information in PMC

References

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Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder

Affiliations

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Medical