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Genetic variants associated with cardiometabolic abnormalities during treatment with selective serotonin reuptake inhibitors: a genome-wide association study

The Pharmacogenomics Journal volume 21, pages 574–585 (2021)Cite this article

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Abstract

Selective serotonin reuptake inhibitors (SSRIs) are prescribed both to patients with schizophrenia and bipolar disorder. Previous studies have shown associations between SSRI treatment and cardiometabolic alterations. The aim of the present study was to investigate genetic variants associated with cardiometabolic adverse effects in patients treated with SSRIs in a naturalistic setting, using a genome-wide cross-sectional approach in a genetically homogeneous sample. We included and genotyped 1981 individuals with schizophrenia or bipolar disorder, of whom 1180 had information available on the outcomes low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, and body mass index (BMI) and investigated interactions between SNPs and SSRI use (N = 246) by conducting a genome-wide GxE analysis. We report 13 genome-wide significant interaction effects of SNPs and SSRI serum concentrations on LDL-cholesterol, HDL-cholesterol, and BMI, located in four distinct genomic loci. This study provides new insight into the pharmacogenetics of SSRI but warrants replication in independent populations.

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Fig. 1: GWAS results for the gene variant—SSRI serum concentration interaction associated with the five cardiometabolic outcomes; body mass index (BMI), triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol.
Fig. 2: Regional plots for loci where significant interaction effects were revealed.
Fig. 3: Differentially expressed gene sets across 30 general tissue types and 53 specific tissue types for body mass index.

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Acknowledgements

The authors would like to thank Department of Medical Biochemistry at Oslo University Hospital Ullevaal, Norway for their analyzes of blood samples.

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  1. These authors contributed equally: Katrine K. Fjukstad, Lavinia Athanasiu

Authors and Affiliations

  1. Clinic for Mental Health and Substance Abuse, Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger, Norway

    Katrine K. Fjukstad

  2. Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway

    Katrine K. Fjukstad

  3. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Lavinia Athanasiu, Shahram Bahrami, Kevin S. O’Connell, Dennis van der Meer, Francesco Bettella, Ingrid Dieset, Nils Eiel Steen & Ole A. Andreassen

  4. Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

    Srdjan Djurovic

  5. NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway

    Srdjan Djurovic

  6. Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway

    Olav Spigset

  7. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    Olav Spigset

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Correspondence to Katrine K. Fjukstad.

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Fjukstad, K.K., Athanasiu, L., Bahrami, S. et al. Genetic variants associated with cardiometabolic abnormalities during treatment with selective serotonin reuptake inhibitors: a genome-wide association study. Pharmacogenomics J 21, 574–585 (2021). https://doi.org/10.1038/s41397-021-00234-8

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