Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Mortality and risk of diabetes, liver disease, and heart disease in individuals with haemochromatosis C282Y homozygosity and normal concentrations of iron, transferrin saturation, or ferritin: prospective cohort study.

Objectives: To test whether haemochromatosis C282Y homozygotes have increased risk of diabetes, liver disease, and heart disease even when they have normal plasma iron, transferrin saturation, or ferritin concentrations and to test whether C282Y homozygotes with diabetes, liver disease, or heart disease have increased mortality compared with non-carriers with these diseases.

Design: Prospective cohort study.

Setting: Three Danish general population cohorts: the Copenhagen City Heart Study, the Copenhagen General Population Study, and the Danish General Suburban Population Study.

Attitudes towards risk-stratified breast cancer screening in Denmark - a qualitative study.

Background: Today the prerequisites exist to initiate risk-stratified screening according to a woman's individual risk of breast cancer as opposed to existing one-size-fits-all age-based programmes. This presupposes that the women accept having their personal risk score estimated and their screening intervals changed accordingly. Risk-stratified screening has not yet been implemented in any country, but in the future many European countries will very likely move towards more personalized screening.

Aryl hydrocarbon receptor repressor ( AHRR ) methylation predicts risk of vascular disease: A cohort study of the general population.

Aims: Smoking is a risk factor for cardiovascular disease, but there is currently no clinically established biomarker for its cardiovascular damage. We aimed to investigate the hypothesis that aryl hydrocarbon receptor repressor ( AHRR ) methylation at CpG site cg05575921, a biomarker of smoking behavior, is associated with the risk of peripheral artery disease (PAD) and aortic aneurysm (AA) in the general population.

Methods And Results: In this prospective cohort study of the general population, we measured AHRR methylation in individuals from three visits to the Copenhagen City Heart Study.

Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals.

It is unclear whether risk of infection is increased in individuals with hereditary hemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through HFE genotypes. We studied 142 188 Danish general population individuals.

Adherence to general national dietary guidelines and risk of psoriasis: results from a general population study of 105 332 individuals.

Background: It is unknown if an unhealthy diet can affect the risk of developing psoriasis.

Objectives: To test the hypothesis that individuals with an unhealthy diet have an increased risk of prevalent and incident psoriasis.

Methods: We included 105 332 adults from the Copenhagen General Population Study, who were invited to participate between 2003 and 2015.

Attitudes towards risk-stratified breast cancer screening: a population-based survey among 5,001 Danish women.

Background: The individual woman's risk of being diagnosed with breast cancer can now be estimated more precisely, and screening can be stratified accordingly. The risk assessment requires that women are willing to provide a blood test, additional personal information, to know their risk, and alter screening intervals. This study aimed to investigate Danish women's attitudes towards risk-stratified breast cancer screening.

Elevated plasma triglycerides increase the risk of psoriasis: a cohort and Mendelian randomization study.

Background: It is increasingly clear that triglyceride-rich lipoproteins are proinflammatory and cause low-grade systemic inflammation. However, it is currently unknown whether elevated plasma triglycerides are causally related to the development of psoriasis, a skin disorder driven by chronic inflammation.

Objectives: To determine if elevated plasma triglycerides are associated with increased risk of psoriasis in observational and Mendelian randomization analysis.

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.

The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.

Self-Reported Health as Predictor of Allostatic Load and All-Cause Mortality: Findings From the Lolland-Falster Health Study.

The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality. Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016-2020 ( = 14,104). Median follow-up time for death was 4.

Prognostic Value of Pretreatment Plasma C-Reactive Protein in Patients with Early-Stage Breast Cancer.

Background: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results.

Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities.

Objectives: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark.

Design: Register-based study.

Setting: Data derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification.

Background: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.

Methods: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

Background: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

Methods: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants.

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.

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.

Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established.