Publications by authors named "Geus E"

Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.

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Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbial pathways using data generated by shotgun metagenomic sequencing (n = 683).

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Previous research has demonstrated that hearing impairment is associated with heightened subjective experiences of listening effort, fatigue, and stress, impacting daily functioning. This study aimed to evaluate whether hearing impairment alters physiological stress systems and whether different aspects of hearing impairment could vary in predicting dysregulation in these systems. Hallmark measures of parasympathetic and sympathetic nervous system activity were derived from electrocardiography, impedance cardiography, and electrodermal activity recordings taken from 133 individuals, aged 37 to 73, over two 24-hr periods, including sleep.

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Article Synopsis
  • * The study reveals that interferon-epsilon (IFNε), found in specific cells within the testes, plays a crucial role in fighting viral infections in both mice and humans.
  • * Mice without IFNε were more vulnerable to Zika virus damage, while adding IFNε to human testicular cells decreased viral presence and inflammation, indicating its importance in protecting male reproductive health.
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Introduction: Alzheimer's disease (AD) is a highly heritable disease (60%-80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers.

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Objective: Type D (Distressed) personality combines negative affectivity (NA) and social inhibition (SI) and is associated with an increased risk of cardiometabolic diseases. Here, we examined the association of Type D traits with 230 (predominantly) lipid metabolites and metabolite ratios.

Methods: Four Dutch cohorts were included, comprising 10,834 individuals.

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  • * A large study involving nearly 10,000 DCM cases and close to a million controls identified 70 significant genetic locations linked to the disease, revealing the importance of heart muscle cells in its development.
  • * The research also indicates that factors like higher body weight and blood pressure may contribute to DCM, and genetic risk scores can help predict the condition across different populations.
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Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by a high metastatic potential with an overall survival rate of ~5%. The transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed by >50% of tumors, including SCLC, but its role in SCLC development and metastasis is unclear. Here, we show that, while STAT3 deletion restricts primary tumor growth, it paradoxically enhances metastatic spread by promoting immune evasion.

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Using heart rate (HR) measurements to detect mental stress in naturalistic settings is hampered by the physiological impact of hemodynamic and metabolic demands. Correcting HR for these demands can help isolate fluctuations in HR associated with psychosocial stress responses, a concept termed additional heart rate (aHR). This study examined whether adding predictors for posture, activity type, and lagged movement intensity for the prolonged impact of physical activity (PA) improved aHR estimation across various manipulations of mental stress, posture, and PA in a controlled laboratory environment (n = 197).

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Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma.

Methods: The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families.

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Background: Obesity may affect an individual's immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection.

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  • This study aimed to assess the reliability of a short food frequency questionnaire designed to evaluate dietary patterns associated with type 2 diabetes risk and to create a Diabetes Dietary Quality Index.
  • Healthy participants completed the questionnaire, and the results indicated good reproducibility, showing consistent correlation in responses.
  • Findings revealed that a higher Diabetes Dietary Quality Index score was linked to improved metabolic health, including lower post-meal glucose and insulin levels, as well as better cholesterol profiles.
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  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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  • Genetic studies have highlighted the need for more diverse research on plasma fibrinogen levels, as previous studies largely focused on Europeans, leading to gaps in understanding and missing heritability.
  • By analyzing data from whole-genome sequencing and genotype data from large cohorts, researchers identified 18 genetic loci related to fibrinogen levels, some of which are more common in African populations and include variants that may impact protein function.
  • The study's findings indicate a connection between fibrinogen levels and various health conditions, emphasizing the importance of whole-genome sequencing in discovering genetic factors in diverse populations and enhancing knowledge about fibrinogen regulation.
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Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants.

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Interferon epsilon (IFNε) is a unique type I interferon (IFN) that shows distinct constitutive expression in reproductive tract epithelium. Understanding how IFNε expression is regulated is critical for the mechanism of action in protecting the mucosa from infection. Combined computational and experimental investigation of the promoter of IFNε predicted transcription factor binding sites for the ETS family of transcription factors.

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Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.

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Objectives: Listening effort involves the mental effort required to perceive an auditory stimulus, for example in noisy environments. Prolonged increased listening effort, for example due to impaired hearing ability, may increase risk of health complications. It is therefore important to identify valid and sensitive measures of listening effort.

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This Committee Report provides methodological, interpretive, and reporting guidance for researchers who use measures of heart rate (HR) and heart rate variability (HRV) in psychophysiological research. We provide brief summaries of best practices in measuring HR and HRV via electrocardiographic and photoplethysmographic signals in laboratory, field (ambulatory), and brain-imaging contexts to address research questions incorporating measures of HR and HRV. The Report emphasizes evidence for the strengths and weaknesses of different recording and derivation methods for measures of HR and HRV.

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During infection viruses hijack host cell metabolism to promote their replication. Here, analysis of metabolite alterations in macrophages exposed to poly I:C recognises that the antiviral effector Protein Kinase RNA-activated (PKR) suppresses glucose breakdown within the pentose phosphate pathway (PPP). This pathway runs parallel to central glycolysis and is critical to producing NADPH and pentose precursors for nucleotides.

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In recent studies, psychophysiological measures have been used as markers of listening effort, but there is limited research on the effect of hearing loss on such measures. The aim of the current study was to investigate the effect of hearing acuity on physiological responses and subjective measures acquired during different levels of listening demand, and to investigate the relationship between these measures. A total of 125 participants (37 males and 88 females, age range 37-72 years, pure-tone average hearing thresholds at the best ear between -5.

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