Lifestyle index for mortality prediction using multiple ageing cohorts in the USA, UK and Europe

Current mortality prediction indexes are mainly based on functional morbidity and comorbidity, with limited information for risk prevention. This study aimed to develop and validate a modifiable lifestyle-based mortality predication index for older adults. Data from 51,688 participants (56% women) aged ≥50 years in 2002 Health and Retirement Study, 2002 English Longitudinal Study of Ageing and 2004 Survey of Health Ageing and Retirement in Europe were used to estimate coefficients of the index with cohort-stratified Cox regression. Models were validated across studies and compared to the Lee index (having comorbid and morbidity predictors). Over an average of 11-year follow-up, 10,240 participants died. The lifestyle index includes smoking, drinking, exercising, sleep quality, BMI, sex and age; showing adequate model performance in internal validation (C-statistic 0.79; D-statistic 1.94; calibration slope 1.13) and in all combinations of internal-external cross-validation. It outperformed Lee index (e.g. differences in C-statistic = 0.01, D-statistic = 0.17, P < 0.001) consistently across health status. The lifestyle index stratified participants into varying mortality risk groups, with those in the top quintile having 13.5% excess absolute mortality risk over 10 years than those in the bottom 50th centile. Our lifestyle index with easy-assessable behavioural factors and improved generalizability may maximize its usability for personalized risk management

Threshold Haemoglobin Levels and the Prognosis of Stable Coronary Disease: Two New Cohorts and a Systematic Review and Meta-Analysis

Background: Low haemoglobin concentration has been associated with adverse prognosis in patients with angina and myocardial infarction (MI), but the strength and shape of the association and the presence of any threshold has not been precisely evaluated.Methods and findings: A retrospective cohort study was carried out using the UK General Practice Research Database. 20,131 people with a new diagnosis of stable angina and no previous acute coronary syndrome, and 14,171 people with first MI who survived for at least 7 days were followed up for a mean of 3.2 years. Using semi-parametric Cox regression and multiple adjustment, there was evidence of threshold haemoglobin values below which mortality increased in a graded continuous fashion. For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2-13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76-2.29) compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e. g, for MI 12.8 g/dl; 95% CI 12.1-13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI. We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk.Conclusions: There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here. Intervention trials would clarify whether increasing the haemoglobin concentration reduces mortality

Genetic analysis identifies molecular systems and biological pathways associated with household income

Abstract Socio-economic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. Previous genome-wide association studies (GWAS) using household income as a marker of SEP have shown that common genetic variants account for 11% of its variation. Here, in a sample of 286,301 participants from UK Biobank, we identified 30 independent genome-wide significant loci, 29 novel, that are associated with household income. Using a recently-developed method to meta-analyze data that leverages power from genetically-correlated traits, we identified an additional 120 income-associated loci. These loci showed clear evidence of functional enrichment, with transcriptional differences identified across multiple cortical tissues, in addition to links with GABAergic and serotonergic neurotransmission. We identified neurogenesis and the components of the synapse as candidate biological systems that are linked with income. By combining our GWAS on income with data from eQTL studies and chromatin interactions, 24 genes were prioritized for follow up, 18 of which were previously associated with cognitive ability. Using Mendelian Randomization, we identified cognitive ability as one of the causal, partly-heritable phenotypes that bridges the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. Significant differences between genetic correlations indicated that, the genetic variants associated with income are related to better mental health than those linked to educational attainment (another commonly-used marker of SEP). Finally, we were able to predict 2.5% of income differences using genetic data alone in an independent sample. These results are important for understanding the observed socioeconomic inequalities in Great Britain today

A plan on creating a video game store in Kokkola

The main aim for this thesis was to investigate the situation in Kokkola regarding the establishment of a new video game store. The bottom line was to study whether it would be a profitable idea to carry out a plan to create such a store, by determining is there a market for a store selling specifically video games. Also, the reactions of the general public were highly valued to adjust the actions and services of the said video game store. In theory, the contents cover data from different resources such as news articles and published writings. The matter was approached by gathering information on the prevalent situation and pondering various scenarios from the surrounding world affecting the stores operations. In addition, the effects of the video game store were brought up and evaluated. Since the field of video game industry is vast, a large amount of background information was covered in the document to give the reader a deeper understanding on the matters studied. The writer's own thoughts and existing knowledge is added in throughout the document. The competitive situation, as well as the development of the city of Kokkola was taken into account and studied by the author. A qualitative study among the general public was conducted in October of 2017 to obtain their insights on the matter. When combined with the data gathered from the source material and the writer's notions, the people's answers proved to be a significant part of the process. The conclusions were reached by analyzing the data from different viewpoints. The end result formed and changed through the process. Mostly, the situation at hand was the heaviest factor in evaluating the final decisions. A business needs its customers to keep on operating. However, the world of today offers the consumers various solutions when it comes to purchasing products. Still, the future is not set in stone and predicting the turns of events is not always accurate

Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19

Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 × 10-6; IFNAR2, P = 9.8 × 10-11 and IL-10RB, P = 2.3 × 10-14) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19

Association analyses based on false discovery rate implicate new loci for coronary artery disease

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10 '8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n cases = 10,801) as well as a stricter definition without angina (HARD; n cases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation