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Genetic variation i...
Genetic variation in the Estonian population : pharmacogenomics study of adverse drug effects using electronic health records
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- Tasa, Tonis (author)
- Univ Tartu, Inst Comp Sci, EE-50409 Tartu, Estonia;Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Krebs, Kristi (author)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Kals, Mart (author)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Mägi, Reedik (author)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Lauschke, Volker M. (author)
- Karolinska Institutet
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- Haller, Toomas (author)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Puurand, Tarmo (author)
- Univ Tartu, Inst Mol & Cell Biol, Dept Bioinformat, EE-51010 Tartu, Estonia
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- Remm, Maido (author)
- Univ Tartu, Inst Mol & Cell Biol, Dept Bioinformat, EE-51010 Tartu, Estonia
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- Esko, Tonu (author)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Metspalu, Andres (author)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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- Vilo, Jaak (author)
- Univ Tartu, Inst Comp Sci, EE-50409 Tartu, Estonia
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- Milani, Lili, 1981- (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia
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(creator_code:org_t)
- 2018-11-12
- 2019
- English.
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In: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 27:3, s. 442-454
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Abstract
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- Pharmacogenomics aims to tailor pharmacological treatment to each individual by considering associations between genetic polymorphisms and adverse drug effects (ADEs). With technological advances, pharmacogenomic research has evolved from candidate gene analyses to genome-wide association studies. Here, we integrate deep whole-genome sequencing (WGS) information with drug prescription and ADE data from Estonian electronic health record (EHR) databases to evaluate genome- and pharmacome-wide associations on an unprecedented scale. We leveraged WGS data of 2240 Estonian Biobank participants and imputed all single-nucleotide variants (SNVs) with allele counts over 2 for 13,986 genotyped participants. Overall, we identified 41 (10 novel) loss-of-function and 567 (134 novel) missense variants in 64 very important pharmacogenes. The majority of the detected variants were very rare with frequencies below 0.05%, and 6 of the novel lossof-function and 99 of the missense variants were only detected as single alleles (allele count = 1). We also validated documented pharmacogenetic associations and detected new independent variants in known gene-drug pairs. Specifically, we found that CTNNA3 was associated with myositis and myopathies among individuals taking nonsteroidal anti-inflammatory oxicams and replicated this finding in an extended cohort of 706 individuals. These findings illustrate that population-based WGS-coupled EHRs are a useful tool for biomarker discovery.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Tasa, Tonis
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Krebs, Kristi
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Kals, Mart
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Mägi, Reedik
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Lauschke, Volker ...
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Haller, Toomas
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Puurand, Tarmo
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Remm, Maido
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Esko, Tonu
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Metspalu, Andres
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Vilo, Jaak
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Milani, Lili, 19 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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European Journal ...
- By the university
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Uppsala University
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Karolinska Institutet