Abstract
The Estonian Biobank, governed by the Institute of Genomics at the University of Tartu (Biobank), has stored genetic material/DNA and continuously collected data since 2002 on a total of 52,274 individuals representing ~5% of the Estonian adult population and is increasing. To explore the utility of data available in the Biobank, we conducted a phenome-wide association study (PheWAS) in two areas of interest to healthcare researchers; asthma and liver disease. We used 11 asthma and 13 liver disease-associated single nucleotide polymorphisms (SNPs), identified from published genome-wide association studies, to test our ability to detect established associations. We confirmed 2 asthma and 5 liver disease associated variants at nominal significance and directionally consistent with published results. We found 2 associations that were opposite to what was published before (rs4374383:AA increases risk of NASH/NAFLD, rs11597086 increases ALT level). Three SNP-diagnosis pairs passed the phenome-wide significance threshold: rs9273349 and E06 (thyroiditis, p = 5.50x10-8); rs9273349 and E10 (type-1 diabetes, p = 2.60x10-7); and rs2281135 and K76 (non-alcoholic liver diseases, including NAFLD, p = 4.10x10-7). We have validated our approach and confirmed the quality of the data for these conditions. Importantly, we demonstrate that the extensive amount of genetic and medical information from the Estonian Biobank can be successfully utilized for scientific research.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Asthma / complications
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Asthma / epidemiology
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Asthma / genetics*
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Biological Specimen Banks / statistics & numerical data*
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Electronic Health Records / statistics & numerical data*
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Estonia / epidemiology
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Female
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Genetic Predisposition to Disease
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Genome-Wide Association Study
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Genotype
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Humans
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Liver Diseases / complications
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Liver Diseases / epidemiology
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Liver Diseases / genetics*
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Male
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Phenomics / methods*
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Phenotype
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Polymorphism, Single Nucleotide*
Grants and funding
These analyses were supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. This research has also been supported by European Regional Development Fund under the grant no EU48684. AstraZeneca provided support in the form of salaries for author GJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. STACC and Quretec provided support in the form of salaries for authors SR and JV, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. GlaxoSmithKline provided support in the form of salaries for authors NG, DW and MA, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Pfizer provided support in the form of salaries for author AKL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Regional Development Funds for the Center of Excellence of Estonian ICT research EXCITE and Estonian Research Council grant IUT34-4: These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders provided support in the form of salaries for authors JV, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.