Palle Duun Rohde

Aalborg University · Department of Health Science and Technology

Calmodulin acts as a vital calcium sensor in cells, crucial for relaying calcium signals to different protein partners. While rare missense variants in calmodulin are linked to cardiac arrhythmia, particularly long QT syndrome (LQTS), their role in schizophrenia remains unexplored. We investigated missense variants in the calmodulin-encoding genes...

Background Gene set tests can pinpoint genes and biological pathways that exert small to moderate effects on complex diseases like Type 2 Diabetes (T2D). By aggregating genetic markers based on biological information, these tests can enhance the statistical power needed to detect genetic associations. Results Our goal was to develop a gene set tes...

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 v...

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 e...

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...

Genome-wide association studies (GWASs) may help inform treatments for infertility, whose causes remain unknown in many cases. Here we present GWAS meta-analyses across six cohorts for male and female infertility in up to 41,200 cases and 687,005 controls. We identified 21 genetic risk loci for infertility ( P ≤5E-08), of which 12 have not been rep...

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. Here, we focused on the...

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 coordinat...

Gene set tests can pinpoint genes and biological pathways that exert small to moderate effects on complex diseases like Type 2 Diabetes (T2D). By aggregating genetic markers based on biological information, these tests can enhance the statistical power needed to detect genetic associations. Our goal was to develop a gene set test utilizing Bayesian...

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 behavioral and physiological changes. While much work has been done on understanding the genetic architecture and evolutionary potential of stre...

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 nucleoti...

Importance Recurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology a...

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 Drosophila melanogaster. Four diets with different nutritional val...

Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-ass...

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 (BLR) modeling procedures, which provide a unified framework for mapping of genetic variants, estimation of heritability and genomic prediction from...

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 nucleotid...

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 CA...

Bayesian linear regression (BLR) models consider the underlying genetic architecture of complex phenotypes by specifying different prior distributions for SNP effects allowing heterogenous distribution of the true genetic signals. Our goal is to evaluate BLR models with BayesC and BayesR prior distributions for fine mapping on simulated and real bi...

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-a...

Unlabelled: The role of integrating genomic scores (GSs) needs to be assessed. Adding a GS to recommended stratification tools does not improve the prediction of very low bone mineral density. However, we noticed that the GS performed equally or above individual risk factors in discrimination. Purpose: We aimed to investigate whether adding a ge...

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 i...

Objectives Allele counts of sequence variants obtained by whole genome sequencing (WGS) often play a central role in interpreting the results of genetic and genomic research. However, such variant counts are not readily available for individuals in the Danish population. Here, we present a dataset with allele counts for sequence variants (single nu...

In humans, mutations in calmodulin cause cardiac arrhythmia. These mutations disrupt the ability of calmodulin to sense calcium concentrations and correctly regulate two central calcium channels, together obstructing heart rhythm. This correlation is well established, but also surprising since calmodulin is expressed in all tissues and interacts wi...

Parkinson’s disease (PD) is a heterogeneous and complex neurodegenerative disorder and large-scale genetic studies have identified >130 genes associated with PD. Although genomic studies have been decisive for our understanding of the genetic contributions underlying PD, these associations remain as statistical associations. Lack of functional vali...

Digital tools and platforms offer new solutions to design and conduct university teaching. This case illustrates how such digital solutions may be utilized in problem-based learning programmes within life science educations. Specifically, the case evaluated the use of live-streamed and recorded lectures, the incorporation of digital formative asses...

Here, we present an expanded utility of the R package qgg for quantitative genetic and genomic analyses of complex traits and diseases. One of the major updates of the package is, that it now includes five different Bayesian Linear Regression (BLR) models, which provide a unified framework for mapping of genetic variants, estimation of heritability...

Background Mutations in ATP1A2 gene encoding the Na,K‐ATPase α 2 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. We hypothesized that ATP1A2 is a susceptibility gene for hea...

In the spring of 2020, the outbreak of COVID-19 forced universities worldwide to close campuses and transition to online teaching. The numerous challenges associated with moving traditional in-person lectures to an online forum also provided an opportunity to revisit technological and pedagogical approaches for improving lecture quality. In traditi...

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 u...

PurposeTo evaluate whether young women with idiopathic early ovarian aging, as defined by producing fewer oocytes than expected for a given age over multiple in vitro fertilization (IVF) cycles, have changes in telomere length and epigenetic age indicating accelerated biological aging (i.e., increased risk of morbidity and mortality).MethodsA prosp...

Recently it has been proposed, that the holobiont, i.e., the host and its associated microbiome, constitute a distinct biological entity, on which selection operates. This is a fascinating idea that so far has limited empirical justification. Here Drosophila melanogaster lines from a large-scale artificial selection experiment, where we selected fo...

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....

Study question Do young women with idiopathic early ovarian ageing have changes in telomere length and epigenetic age indicating accelerated biological aging? Summary answer The telomere length and epigenetic age were comparable to those in young women with normal ovarian ageing. What is known already Increased risk of several health events usual...

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 litt...

Genetic variants in the genomic region containing SORT1 (encoding the protein sortilin) are strongly associated with cholesterol levels and the risk of coronary artery disease (CAD). Circulating sortilin has therefore been proposed as a potential biomarker for cardiovascular disease. Multiple studies have reported association between plasma sortili...

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...

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 to a limited extent been translated to genomic medicine. We propose, that one ro...

Acid-base conditions modify artery tone and tissue perfusion but the involved vascular sensing mechanisms and disease consequences remain unclear. We experimentally investigated transgenic mice and performed genetic studies in a UK-based human cohort. We show that endothelial cells express the putative HCO3--sensor receptor-type tyrosine-protein ph...

Understanding the genotype - phenotype map and how variation at different levels of biological organization are 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, s...

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 ge...

Knowledge of the genetic basis underlying variation in response to environmental exposures or treatment is important in many research areas. For example, knowing the set of causal genetic variants for drug response could revolutionize personalized medicine. We used Drosophila melanogaster to investigate the genetic signature underlying behavioral v...

Studies of complex traits and diseases are strongly dependent on the availability of user-friendly software designed to handle large-scale genetic and phenotypic data. Here, we present the R package qgg, which provides an environment for large-scale genetic analyses of quantitative traits and disease phenotypes. The qgg package provides an infrastr...

Most organisms experience variable and sometimes suboptimal environments in their lifetime. While stressful environmental conditions are normally viewed as a strong selective force, they can also impact directly on the genetic basis of traits such as through environment-dependent gene action. Here, we used the Drosophila melanogaster Genetic Refere...

Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait variability to pinpoint loci that contribute to the qu...

Trait variation is normally separated into genetic and environmental components, yet genetic factors also control the expression of environmental variation, encompassing plasticity across environmental gradients and within-environment responses. We defined four components of environmental variation: plasticity across environments, variability in pl...

Human psychiatric disorders such as schizophrenia, bipolar disorder and attention-deficit/hyper-activity disorder often include adverse behaviors including increased aggressiveness. Individuals with psychiatric disorders often exhibit social withdrawal, which can further increase the probability of conducting a violent act. Here, we used the inbred...

The genomic best linear unbiased prediction (GBLUP) model has proven to be useful for prediction of complex traits as well as estimation of population genetic parameters. Improved inference and prediction accuracy of GBLUP may be achieved by identifying genomic regions enriched for causal genetic variants. We aimed at searching for patterns in GBLU...

The concept of developmental instability (DI) is a well-known indicator of environmental and genetic stress and is often investigated using various indices such as fluctuating asymmetry, directional asymmetry, antisymmetry and phenotypic variance. Investigations dealing with DI are using morphometric traits. The aim of this investigation is to pres...

Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single marker methods have limited power to detect genetic markers with small effects....

Fruit flies are important model organisms for functional testing of candidate genes in multiple disciplines, including the study of human diseases. Here we use a high-throughput locomotor activity assay to test the response on activity behavior of gene disruption in Drosophila melanogaster. The aim was to investigate the impact of disruption of 14...

The ability of natural populations to withstand environmental stresses relies partly on their adaptive ability. In this study, we used a subset of the Drosophila Genetic Reference Panel, a population of inbred, genome-sequenced lines derived from a natural population of Drosophila melanogaster, to investigate whether this population harbors genetic...

The supplementary material contain information of which DGRP lines assessed, additional experimental design informations (Table S1), and the phenotypic line means for the traits assayed (Table S2). The supplementary information also contains the likelihood ratio test for the fixed effects (Table S3), overview of GOs with a p<0.005 (Table S4) and GO...

Abstract Text: : Whole-genome sequences and multiple trait phenotypes from large numbers of individuals will soon be available. Well established statistical modeling approaches enable the genetic analyses of complex trait phenotypes while accounting for a variety of additive and non-additive genetic mechanisms. These modeling approaches have proven...

Identification of genes explaining variation in quantitative traits or genetic risk factors of human diseases requires both good phenotypic- and genotypic data, but also efficient statistical methods. Genome-wide association studies may reveal association between phenotypic variation and variation at nucleotide level, thus potentially identify gene...

Aggressive behavior in animals plays an important role in acquisition and defense of resources, and in establishing dominance hierarchies among social animals. In humans, elevated aggressive behavior is associated with some psychiatric- and neurodegenerative disorders, which have large social- and economic costs. Aggressive behavior is a typical qu...

Inbreeding increases homozygosity, which is known to affect the mean and variance of fitness components such as growth, fecundity and mortality rate. Across inbred lines inbreeding depression is typically observed and the variance between lines is increased in inbred compared to outbred lines. It has been suggested that damage incurred from increas...