SWEDEGENE\u2014a Swedish nation-wide DNA sample collection for pharmacogenomic studies of serious adverse drug reactions

Mia Wadelius,Erik Eliasson,Qun-Ying Yue,Pär Hallberg,Håkan Melhus,Joel Ås

doi:10.1038/s41397-020-0148-3

Abstract

SWEDEGENE is a Swedish nation-wide sample collection established to facilitate studies of clinical and genetic risk factors for adverse drug reactions (ADRs). Most cases are recruited among patients reported to the ADR registry at the Swedish Medical Products Agency by health-care professionals. Clinical data are collected both from medical and laboratory records and through interviews using standardized questionnaires. Genome-wide scans and whole-genome sequencing are done, and association studies are conducted using mainly controls from the Swedish TwinGene biobank with data on diagnoses and prescribed drugs. SWEDEGENE was established in 2008 and currently contains DNA and information from about 2550 adults who have experienced specific ADRs, and from 580 drug exposed controls. Results from genome-wide association studies have now been published, and data from whole-genome sequencing are being analyzed. SWEDEGENE has the potential to offer a new means of developing individualized and safe drug therapy through patient pre-treatment screening.

Highlights

Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, leading to individual treatment failures and to substantially increased healthcare costs
About 10% of the Swedish healthcare budget has been attributed to ADRs [6]
Pharmacology, Karolinska University Hospital, Stockholm, Sweden the dose-dependent bone-marrow suppression that develops in patients with defective detoxification of thiopurines related to genetic variants of the key enzyme thiopurine methyltransferase [8]

Summary

Introduction

Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, leading to individual treatment failures and to substantially increased healthcare costs. ADRs have been estimated to cause or contribute to at least 5–7% of hospital admissions [1,2,3,4], and to about 3% of all fatalities [5]. Dose-dependent ADRs are known to be caused by mutations in genes involved in the metabolism of the drug or in the drug target. An example is Pharmacology, Karolinska University Hospital, Stockholm, Sweden the dose-dependent bone-marrow suppression that develops in patients with defective detoxification of thiopurines related to genetic variants of the key enzyme thiopurine methyltransferase [8]

Objectives

Methods

Results