Evaluation of Bayesian Linear Regression models for gene set prioritization in complex diseases.

Genome-wide association studies (GWAS) provide valuable insights into the genetic architecture of complex traits, yet interpreting their results remains challenging due to the polygenic nature of most traits. Gene set analysis offers a solution by aggregating genetic variants into biologically relevant pathways, enhancing the detection of coordinated effects across multiple genes. In this study, we present and evaluate a gene set prioritization approach utilizing Bayesian Linear Regression (BLR) models to uncover shared genetic components among different phenotypes and facilitate biological interpretation.

Bugs on Drugs: Paracetamol Exposure Reveals Genotype-Specific Generational Effects on Life History Traits in .

Few investigations have been made to determine whether pharmaceutical drugs cause any generational effects. These effects can be divided into intergenerational and transgenerational effects. In insects, the F1 offspring of exposed individuals are considered to show intergenerational effects (as they have been exposed as germ cells or early embryos), while the F2 generation is fully non-exposed and considered to show transgenerational effects.

Selection for stress tolerance and longevity in Drosophila melanogaster have strong impacts on microbiome profiles.

There is experimental evidence that microbiomes have a strong influence on a range of host traits. Understanding the basis and importance of symbiosis between host and associated microorganisms is a rapidly developing research field, and we still lack a mechanistic understanding of ecological and genetic pressures affecting host-microbiome associations. Here Drosophila melanogaster lines from a large-scale artificial selection experiment were used to investigate whether the microbiota differ in lines selected for different stress resistance traits and longevity.

Feeding Drosophila gut microbiomes from young and old flies modifies the microbiome.

It is becoming increasingly evident that the myriad of microbes in the gut, within cells and attached to body parts (or roots of plants), play crucial roles for the host. Although this has been known for decades, recent developments in molecular biology allow for expanded insight into the abundance and function of these microbes. Here we used the vinegar fly, Drosophila melanogaster, to investigate fitness measures across the lifetime of flies fed a suspension of gut microbes harvested from young or old flies, respectively.

A Genetic Analysis of Current Medication Use in the UK Biobank.

Genomics has been forecasted to revolutionise human health by improving medical treatment through a better understanding of the molecular mechanisms of human diseases. Despite great successes of the last decade's genome-wide association studies (GWAS), the results have been translated to genomic medicine to a limited extent. One route to get closer to improved medical treatment could be by understanding the genetics of medication use.

Predicting the presence of coronary plaques featuring high-risk characteristics using polygenic risk scores and targeted proteomics in patients with suspected coronary artery disease.

Background: The presence of coronary plaques with high-risk characteristics is strongly associated with adverse cardiac events beyond the identification of coronary stenosis. Testing by coronary computed tomography angiography (CCTA) enables the identification of high-risk plaques (HRP). Referral for CCTA is presently based on pre-test probability estimates including clinical risk factors (CRFs); however, proteomics and/or genetic information could potentially improve patient selection for CCTA and, hence, identification of HRP.

The soil microbiome of Lolium perenne L. depends on host genotype, is modified by nitrogen level and varies across season.

Genotype by environment interactions (G × E) are frequently observed in herbage production. Understanding the underlying biological mechanisms is important for achieving stable and predictive outputs across production environments. The microbiome is gaining increasing attention as a significant contributing factor to G × E.

Diurnal variation in genetic parameters for locomotor activity in Drosophila melanogaster assessed under natural thermal conditions.

In nature, organisms are exposed to variable and occasionally stressful environmental conditions. Responses to diurnal and seasonal fluctuations, such as temperature and food accessibility, involve adaptive behavioural and physiological changes. While much work has been done on understanding the genetic architecture and evolutionary potential of stress tolerance traits under constant thermal conditions, there has been less focus on the quantitative genetic background in variable environments.

Strong Sex-Dependent Effects of Malnutrition on Life- and Healthspan in .

Insufficient intake of essential nutrients, malnutrition is a major issue for millions of people and has a strong impact on the distribution and abundance of species in nature. In this study, we investigated the effect of malnutrition on several fitness components in the vinegar fly . Four diets with different nutritional values, including three diluted diets of an optimal nutritional balanced diet, were used as feed sources.

A genome-wide association study of social trust in 33,882 Danish blood donors.

Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.

Expanded utility of the R package, qgg, with applications within genomic medicine.

Summary: Here, we present an expanded utility of the R package qgg for genetic analyses of complex traits and diseases. One of the major updates of the package is, that it now includes Bayesian linear regression modeling procedures, which provide a unified framework for mapping of genetic variants, estimation of heritability and genomic prediction from either individual level data or from genome-wide association study summary data. With this release, the qgg package now provides a wealth of the commonly used methods in analysis of complex traits and diseases, without the need to switch between software and data formats.

Combining Polygenic and Proteomic Risk Scores With Clinical Risk Factors to Improve Performance for Diagnosing Absence of Coronary Artery Disease in Patients With de novo Chest Pain.

Background: Patients with de novo chest pain, referred for evaluation of possible coronary artery disease (CAD), frequently have an absence of CAD resulting in millions of tests not having any clinical impact. The objective of this study was to investigate whether polygenic risk scores and targeted proteomics improve the prediction of absence of CAD in patients with suspected CAD, when added to the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS).

Methods: Genotyping and targeted plasma proteomics (N=368 proteins) were performed in 1440 patients with symptoms suspected to be caused by CAD undergoing coronary computed tomography angiography.

Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage.

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, , , and / at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR).

Danish study of Non-Invasive Testing in Coronary Artery Disease 3 (Dan-NICAD 3): study design of a controlled study on optimal diagnostic strategy.

Introduction: Current guideline recommend functional imaging for myocardial ischaemia if coronary CT angiography (CTA) has shown coronary artery disease (CAD) of uncertain functional significance. However, diagnostic accuracy of selective myocardial perfusion imaging after coronary CTA is currently unclear. The Danish study of Non-Invasive testing in Coronary Artery Disease 3 trial is designed to evaluate head to head the diagnostic accuracy of myocardial perfusion imaging with positron emission tomography (PET) using the tracers Rubidium (Rb-PET) compared with oxygen-15 labelled water PET (O-water-PET) in patients with symptoms of obstructive CAD and a coronary CT scan with suspected obstructive CAD.

Polygenic Risk Score Prediction for Endometriosis.

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment.

Migraine-Associated Mutation in the Na,K-ATPase Leads to Disturbances in Cardiac Metabolism and Reduced Cardiac Function.

Background Mutations in gene encoding the Na,K-ATPase α isoform are associated with familial hemiplegic migraine type 2. Migraine with aura is a known risk factor for heart disease. The Na,K-ATPase is important for cardiac function, but its role for heart disease remains unknown.

Multi-Trait Genomic Risk Stratification for Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is continuously rising with more disease cases every year. T2DM is a chronic disease with many severe comorbidities and therefore remains a burden for the patient and the society. Disease prevention, early diagnosis, and stratified treatment are important elements in slowing down the increase in diabetes prevalence.

Genotype and Trait Specific Responses to Rapamycin Intake in .

Rapamycin is a powerful inhibitor of the TOR (Target of Rapamycin) pathway, which is an evolutionarily conserved protein kinase, that plays a central role in plants and animals. Rapamycin is used globally as an immunosuppressant and as an anti-aging medicine. Despite widespread use, treatment efficiency varies considerably across patients, and little is known about potential side effects.

Prediction of complex phenotypes using the Drosophila melanogaster metabolome.

Understanding the genotype-phenotype map and how variation at different levels of biological organization is associated are central topics in modern biology. Fast developments in sequencing technologies and other molecular omic tools enable researchers to obtain detailed information on variation at DNA level and on intermediate endophenotypes, such as RNA, proteins and metabolites. This can facilitate our understanding of the link between genotypes and molecular and functional organismal phenotypes.

qgg: an R package for large-scale quantitative genetic analyses.

Summary: Here, we present the R package qgg, which provides an environment for large-scale genetic analyses of quantitative traits and diseases. The qgg package provides an infrastructure for efficient processing of large-scale genetic data and functions for estimating genetic parameters, and performing single and multiple marker association analyses and genomic-based predictions of phenotypes.

Availability And Implementation: The qgg package is freely available.