CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.

Unlabelled: Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis.

Meta-GWAS on PCSK9 concentrations reveals associations of novel loci outside the PCSK9 locus in White populations.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of lipid homeostasis. A few earlier genome-wide association studies (GWAS) investigated genetic variants associated with circulating PCSK9 concentrations. However, uncertainty remains about some of the genetic loci discovered beyond the PCSK9 locus.

Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials.

Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making.

Gender-linked determinants for utilization of long-term care in community-dwelling adults 65+ in Germany: Results from the population-based KORA-Age study.

Background: The number of people using long-term care (LTC) is increasing steadily, hence, demand for adequate services is rising. The purpose of this exploratory study was to identify relevant gender-linked determinants for utilization of LTC in community-dwelling older adults.

Methods: We examined 4077 females (52.

Prediction of type 2 diabetes mellitus based on nutrition data.

Numerous predictive models for the risk of type 2 diabetes mellitus (T2DM) exist, but a minority of them has implemented nutrition data so far, even though the significant effect of nutrition on the pathogenesis, prevention and management of T2DM has been established. Thus, in the present study, we aimed to build a predictive model for the risk of T2DM that incorporates nutrition data and calculates its predictive performance. We analysed cross-sectional data from 1591 individuals from the population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013-14) and used a bootstrap enhanced elastic net penalised multivariate regression method in order to build our predictive model and select among 193 food intake variables.

Cis-epistasis at the LPA locus and risk of cardiovascular diseases.

Aims: Coronary artery disease (CAD) has a strong genetic predisposition. However, despite substantial discoveries made by genome-wide association studies (GWAS), a large proportion of heritability awaits identification. Non-additive genetic effects might be responsible for part of the unaccounted genetic variance.

Combined effect of work stress and impaired sleep on coronary and cardiovascular mortality in hypertensive workers: The MONICA/KORA cohort study.

Background: Although work stress and impaired sleep are established risk factors for cardiovascular disease (CVD) among healthy individuals, their impact on hypertensive workers is largely unknown.

Design: Prospective cohort study design.

Methods: Hypertensive workers (N = 1959), derived from the population-based MONICA/KORA study in Southern Germany, who were free of any cardiovascular disease and diabetes were interviewed at baseline for work stress (high demand plus low control) and impaired sleep (difficulties falling asleep and/or maintaining sleep).

Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases.

Background: DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases.

Serum neurofilament light and tau as prognostic markers for all-cause mortality in the elderly general population-an analysis from the MEMO study.

Background: Neurofilament light chain (NfL) is a cytoskeletal protein component whose release into blood is indicative of neuronal damage. Tau is a microtubule-associated protein in neurons and strongly associated with overall brain degeneration. NfL and tau levels are associated with mortality in different neurological diseases, but studies in the general population are missing.

Spatiotemporal Characteristics and Driving Factors of Black Carbon in Augsburg, Germany: Combination of Mobile Monitoring and Street View Images.

The study investigates the spatial pattern of black carbon (BC) at a high spatial resolution in Augsburg, Germany. Sixty two walks were performed to assess the concentrations of equivalent black carbon (eBC), ultraviolet particulate matter (UVPM), and equivalent brown carbon (eBrC) in different seasons and at different times of the day with a mobile platform (i.e.

Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.

Replication of 15 loci involved in human plasma protein N-glycosylation in 4802 samples from four cohorts.

Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications.

Protein-altering germline mutations implicate novel genes related to lung cancer development.

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.

Walkability and its association with walking/cycling and body mass index among adults in different regions of Germany: a cross-sectional analysis of pooled data from five German cohorts.

Objectives: To examine three walkability measures (points of interest (POI), transit stations and impedance (restrictions to walking) within 640 m of participant's addresses) in different regions in Germany and assess the relationships between walkability, walking/cycling and body mass index (BMI) using generalised additive models.

Setting: Five different regions and cities of Germany using data from five cohort studies.

Participants: For analysing walking/cycling behaviour, there were 6269 participants of a pooled sample from three cohorts with a mean age of 59.

A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter.

Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, the LPA gene. Many aspects of the transcriptional regulation of LPA are poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n = 2208).

Long-term trends in PM mass and particle number concentrations in urban air: The impacts of mitigation measures and extreme events due to changing climates.

Urbanisation and industrialisation led to the increase of ambient particulate matter (PM) concentration. While subsequent regulations may have resulted in the decrease of some PM matrices, the simultaneous changes in climate affecting local meteorological conditions could also have played a role. To gain an insight into this complex matter, this study investigated the long-term trends of two important matrices, the particle mass (PM) and particle number concentrations (PNC), and the factors that influenced the trends.