An exploratory phenome wide association study linking asthma and liver disease genetic variants to electronic health records from the Estonian Biobank

<div><p>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.</p></div

Nucleus formation and the kinetics of thermal decomposition of nickel formate

The kinetics of thermal decomposition of nickel formate are significantly influenced by the disposition of crystallites of the reactant. Both the induction periods and the rates of subse- quent product evolution during the main reaction were different for samples of powder (i) tightly packed, (ii) loosely aggregated or (iii) dispersed on glass wool, when heated under otherwise identical conditions. Electron microscopic exami- ion of surfaces of partially decomposed material showed that the onset of reaction was markedly inhomogeneous. Within a single sample some crystallites had undergone extenive surface nucleation and reaction while others were unaltered. The effect of various additives was also investigated.It is concluded that the kinetic characteristics were control- led by the rate of formation of product metallic nuclei (nickel), a process which strongly inhibited by traces of water of crystallization retained after dehydration or readily adsorbed ar sites of potential initiation of decomposition. Nucleation was followed by relatively rapid two-dimensional growth across surfaces with later advance of the reaction interface into the crystallite bulk