PhenoExplorer: An Interactive Web-based Platform for Exploring (Epi)Genome-Wide Associations Using a Swiss Population-based Study

The recent advent of high-throughput sequencing technologies has allowed exploring the contribution of thousands of genomic, epigenomic, transcriptomic, or proteomic variants to complex phenotypic traits. Here, we sought to conduct large-scale (Epi)Genome-Wide Association Studies (GWAS/EWAS) to investigate the associations between genomic (Single Nucleotide Polymorphism; SNP) and epigenomic (Cytosine-Phospho-Guanine; CpG) markers, with multiple phenotypic traits in a population-based context. We used data from SKIPOGH, a family- and population-based cohort conducted in the cities of Lausanne, Geneva, and Bern (N=1100). We used 7,577,572 SNPs, 420,444 CpGs, and 825 phenotypes, including anthropometric, clinical, blood, urine, metabolite, and metal measures. GWAS analyses assessed the associations between SNPs and metabolites and metals (N=279), using regression models adjusted for age, sex, recruitment center, and familial structure, whereas EWAS analyses explored the relations between CpGs and 825 phenotypes, additionally adjusting for the seasonality of blood sampling and technical nuisance. Following the implementation of GWAS and EWAS analyses, we developed a web-based platform, PhenoExplorer, aimed at providing an open access to the obtained results. Of the 279 phenotypes included in GWAS, 103 displayed significant associations with 2804 SNPs (2091 unique SNPs) at Bonferroni threshold, whereas 109 of the 825 phenotypes included in EWAS analyses were associated with 4893 CpGs (2578 unique CpGs). All of the obtained GWAS and EWAS results were eventually made available using the in-house built web-based PhenoExplorer platform, with the purpose of providing an open-access to the tested associations. In conclusion, we provide a comprehensive outline of GWAS and EWAS associations performed in a Swiss population-based study. Further, we set up a web-based PhenoExplorer platform with the purpose of contributing to the overall understanding of the role of molecular variants in regulating complex phenotypes

Towards a Swiss health study with human biomonitoring: Learnings from the pilot phase about participation and design.

BACKGROUND A large-scale national cohort aiming at investigating the health status and determinants in the general population is essential for high-quality public health research and regulatory decision-making. We present the protocol and first results of the pilot phase to a Swiss national cohort aiming at establishing the study procedures, evaluating feasibility, and assessing participation and willingness to participate. METHODS The pilot phase 2020/21 included 3 components recruited via different channels: a population-based cross-sectional study targeting the adult population (20-69 years) of the Vaud and Bern cantons via personal invitation, a sub-study on selenium in a convenience sample of vegans and vegetarians via non-personal invitation in vegan/vegetarian networks, and a self-selected sample via news promotion (restricted protocol). Along with a participatory approach and participation, we tested the study procedures including online questionnaires, onsite health examination, food intake, physical activity assessments and biosample collection following high-quality standards. RESULTS The population-based study and the selenium sub-study had 638 (participation rate: 14%) and 109 participants, respectively, both with an over-representation of women. Of altogether 1349 recruited participants over 90% expressed interest in participating to a national health study, over 75% to contribute to medicine progress and help improving others' health, whereas about one third expressed concerns over data protection and data misuse. CONCLUSIONS Publicly accessible high-quality public health data and human biomonitoring samples were collected. There is high interest of the general population in taking part in a national cohort on health. Challenges reside in achieving a higher participation rate and external validity. For project management clear governance is key

Interplay of digital proximity app use and SARS-CoV-2 vaccine uptake in Switzerland : analysis of two population-based cohort studies

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic. Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes. Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40–1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62–1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38–0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27–0.78 [CSM]) compared to participants who did not get vaccinated. Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions

Interplay of Digital Proximity App Use and SARS-CoV-2 Vaccine Uptake in Switzerland: Analysis of Two Population-Based Cohort Studies

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic.Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes.Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40–1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62–1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38–0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27–0.78 [CSM]) compared to participants who did not get vaccinated.Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions

Investigating the association of measures of epigenetic age with COVID-19 severity: evidence from secondary analyses of open access data

BACKGROUND: Epigenetic modifications may contribute to inter-individual variation that is unexplainable by presently known risk factors for COVID-19 severity (e.g., age, excess weight, or other health conditions). Estimates of youth capital (YC) reflect the difference between an individual’s epigenetic – or biological – age and chronological age, and may quantify abnormal aging due to lifestyle or other environmental exposures, providing insights that could inform risk-stratification for severe COVID-19 outcomes. This study aims to thereby a) assess the association between YC and epigenetic signatures of lifestyle exposures with COVID-19 severity, and b) to assess whether the inclusion of these signatures in addition to a signature of COVID-19 severity (EPICOVID) improved the prediction of COVID-19 severity. METHODS: This study uses data from two publicly-available studies accessed via the Gene Expression Omnibus (GEO) platform (accession references: GSE168739 and GSE174818). The GSE168739 is a retrospective, cross-sectional study of 407 individuals with confirmed COVID-19 across 14 hospitals in Spain, while the GSE174818 sample is a single-center observational study of individuals admitted to the hospital for COVID-19 symptoms (n = 102). YC was estimated using the (a) Gonseth-Nusslé, (b) Horvath, (c) Hannum, and (d) PhenoAge estimates of epigenetic age. Study-specific definitions of COVID-19 severity were used, including hospitalization status (yes/no) (GSE168739) or vital status at the end of follow-up (alive/dead) (GSE174818). Logistic regression models were used to assess the association between YC, lifestyle exposures, and COVID-19 severity. RESULTS: Higher YC as estimated using the Gonseth-Nusslé, Hannum and PhenoAge measures was associated with reduced odds of severe symptoms (OR = 0.95, 95% CI = 0.91–1.00; OR = 0.81, 95% CI = 0.75 - 0.86; and OR = 0.85, 95% CI = 0.81–0.88, respectively) (adjusting for chronological age and sex). In contrast, a one-unit increase in the epigenetic signature for alcohol consumption was associated with 13% increased odds of severe symptoms (OR = 1.13, 95% CI = 1.05–1.23). Compared to the model including only age, sex and the EPICOVID signature, the additional inclusion of PhenoAge and the epigenetic signature for alcohol consumption improved the prediction of COVID-19 severity (AUC = 0.94, 95% CI = 0.91–0.96 versus AUC = 0.95, 95% CI = 0.93–0.97; p = 0.01). In the GSE174818 sample, only PhenoAge was associated with COVID-related mortality (OR = 0.93, 95% CI = 0.87–1.00) (adjusting for age, sex, BMI and Charlson comorbidity index). CONCLUSIONS: Epigenetic age is a potentially useful tool in primary prevention, particularly as an incentive towards lifestyle changes that target reducing the risk of severe COVID-19 symptoms. However, additional research is needed to establish potential causal pathways and the directionality of this effect

Prevalence of SARS-CoV-2 infection and associated risk factors among asylum seekers living in asylum centres: A cross-sectional serologic study in Canton of Vaud, Switzerland

Background: Understanding the factors influencing SARS-CoV-2 transmission in asylum seekers and refugees living in centres is crucial to determine targeted public health policies protecting these populations fairly and efficiently. In response, this study was designed to explore the pandemic's spread into asylum centres during the first wave of the pandemic in Switzerland. Specifically, it aimed to identify the risk factors associated with a positive anti-SARS-CoV-2 seroprevalence test after the first semi-confinement period (16 March to 27 April 2020) amongst asylum seekers and refugees living in centres. Methods: This research is part of SérocoVID, a seroepidemiologic study of SARS-CoV-2 infection conducted in the canton of Vaud, Switzerland. Migrants living in two asylum centres, one known to have had an epidemic outbreak, were invited to participate in this study. Anti-SARS-CoV-2 IgG and IgA antibodies targeting the spike viral protein were measured in all participants using a Luminex immunoassay. Each participant also completed a questionnaire measuring socio-demographic characteristics, medical history (comorbidities, smoking status, BMI, flu-like symptoms), health literacy, public health recommendations (wearing a masque in a public area, social distancing and hands cleaning), behaviours and exposures (daily life activities, number of contacts weekly). The association of these independent variables with the serologic test result were estimated using a multivariable logistic regression model. Findings: A total of 124 participants from the two asylum centres took part in the study (Centre 1, n = 82; Centre 2, n = 42). The mean participation rate was 36.7%. The seroprevalence in Centres 1 and 2 were 13% [95% CI 0.03, 0.14] and 50% [0.34, 0.65], respectively. Next, 40.63% of SARS-CoV-2 positive people never developed symptoms (asymptomatic cases), and no one had severe forms of the Covid-19 disease requiring hospitalisation. Participants report high compliance with public health measures, especially hygiene rules (96.3% of positive answers) and social distancing (88.7%). However, only 11.3% said they always wore a masque in public. After adjusting for individual characteristics, infection risk was lower amongst people with high health literacy (aOR 0.16, p = 0.007 [0.04, 0.60]) and smokers (aOR 0.20, p = 0.013 [0.06, 0.69]). Conclusion: Despite the lack of severe complications of Covid-19 disease in this study, findings suggest that developing targeted public health measures, especially for the low health literacy population, would be necessary to limit the risk of outbreaks in asylum centres and improve this population's safety. Further investigations and qualitative approach are required to understand more finely how living conditions, risks and behaviours such as tobacco consumption, and the adoption of protective measures impact SARS-CoV-2 infection

Maintaining brain health across the lifespan

Across the lifespan, the human body and brain endure the impact of a plethora of exogenous and endogenous factors that modulate individuals’ health outcome in old age. The overwhelming inter-individual variance spans between increased frailties with loss of autonomy to largely preserved physical, cognitive, and social functions. Understanding the mechanisms underlying the diverse aging trajectories can inform future strategies to maintain a healthy body and brain. Here we provide a comprehensive overview on the lifetime factors governing brain health. We summarise the evidence that unhealthy alimentary regime, sedentary behaviour, sleep pathologies, cardio-vascular risk factors, and chronic inflammation exert their harmful effects in a cumulative and gradual manner, and that timely and efficient intervention promotes successful aging. We discuss the main effects and interactions between these risk factors and the resulting brain health outcomes to follow with a description of current strategies aiming to eliminate, treat, or counteract the risk factors. We conclude that detailed insight about the modifiable risk factors should guide personalized approaches to maintain our brains healthy

Blood DNA methylation signatures of lifestyle exposures:Tobacco and alcohol consumption

BACKGROUND: Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic changes incurred with differing levels of lifestyle exposures. This study describes and validates two novel epigenetic signatures of tobacco (EpiTob) and alcohol (EpiAlc) consumption and investigates their association with disease outcomes. METHODS: The epigenetic signatures, EpiTob and EpiAlc, were developed using data from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) (N = 689). Epigenetic and phenotypic data available from the 1921 (N = 550) and 1936 (N = 1091) Lothian Birth Cohort (LBC) studies, and two publicly available datasets on GEO Accession (GSE50660, N = 464; and GSE110043, N = 94) were used to validate the signatures. A multivariable logistic regression model, adjusting for age and sex, was used to assess the association between self-reported tobacco or alcohol consumption and the respective epigenetic signature, as well as to estimate the association between CVD and epigenetic signatures. A Cox proportional hazard model was used to estimate the risk of mortality in association with the EpiTob and EpiAlc signatures. RESULTS: The EpiTob signature was positively associated with self-reported tobacco consumption for current or never smokers with explained variance ranging from 0.49 (LBC1921) to 0.72 (LBC1936) (pseudo-R(2)). In the SKIPOGH, LBC1921 and LBC1936 cohorts, the epigenetic signature for alcohol consumption explained limited variance in association with self-reported alcohol status [i.e., non-drinker, moderate drinker, and heavy drinker] (pseudo-R(2) = 0.05, 0.03 and 0.03, respectively), although this improved considerably when measuring self-reported alcohol consumption with standardized units consumed per week (SKIPOGH R(2) = 0.21; LBC1921 R(2) = 0.31; LBC1936 R(2) = 0.41). Both signatures were associated with history of CVD in SKIPOGH and LBC1936, but not in LBC1921. The EpiTob signature was associated with increased risk of all-cause and lung-cancer specific mortality in the 1936 and 1921 LBC cohorts. CONCLUSIONS: This study found the EpiTob and EpiAlc signatures to be well-correlated with self-reported exposure status and associated with long-term health outcomes. Epigenetic signatures of lifestyle exposures may reduce measurement issues and biases and could aid in risk stratification for informing early-stage targeted interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01376-7