Integrating population-based metabolomics with computational microbiome modelling identifies methanol as a urinary biomarker for protective diet-microbiome-host interactions.

: Diet-microbiome interactions are core to human health, in particular through bacterial fibre degradation pathways. However, biomarkers reflective of these interactions are not well described. : Using the population-based SHIP-START-0 cohort ( = 4017), we combined metabolome-wide screenings with elastic net machine learning models on 33 food items captured using a food frequency questionnaire (FFQ) and 43 targeted urine nuclear magnetic resonance (NMR) metabolites, identifying methanol as a marker of plant-derived food items.

Association between polygenic risk for Major Depression and brain structure in a mega-analysis of 50,975 participants across 11 studies.

Major Depression (MD) is a prevalent, disabling and life-limiting condition. The neurobiological associations of genetic risk for MD remain under-explored in large samples, with no comprehensive mega-analysis conducted to date. Our study analysed data from 11 separate studies, encompassing 50,975 participants from the ENIGMA Major Depressive Disorder Working Group.

The P4D Dashboard: A Platform for Monitoring Clinical Studies.

The P4D (Personalized, Predictive, Precise & Preventive Medicine for Major Depression) dashboard (https://p4dashboard.vercel.app) is a web-based platform for monitoring and generating data-driven insights within a multi-site clinical depression study.

Lifestyle, Early-life, and Genetic Health Risk Factors Underlying the Brain Age Gap: A Mega-Analysis Across 3,934 Individuals from the ENIGMA MDD Consortium.

Background: Large-scale studies show that adults with major depressive disorder (MDD) generally have a higher imaging-predicted age relative to their chronological age (i.e., positive brain age gap) compared to controls, though considerable within-group variation exists.

Long-term alteration of heart rate variability following childhood maltreatment: Results of a general population study.

Background: Childhood maltreatment (CM) is a risk factor for mental and physical health problems in adulthood, potentially mediated by long-term autonomic nervous system (ANS) dysregulation. To explore this link, the association between CM and vagal-sensitive heart rate variability (HRV) metrics in adults was examined, accounting for biopsychosocial factors.

Methods: Data from 4,420 participants in the Study of Health in Pomerania were analyzed, with CM assessed using the Childhood Trauma Questionnaire.

Sleep architecture and dementia risk in adults: An analysis of 5 cohorts from the Sleep and Dementia Consortium.

Study Objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC).

The impact of childhood emotional abuse and depressive symptoms on sleep macro-architecture and cortical thickness.

Background: Adverse childhood events and especially emotional abuse (EA) is consistently associated with poor psychiatric outcomes in adulthood, with depressive symptoms being one of the most prevalent. Both EA and depression are frequently associated with poorer sleep quality and cortical structural abnormalities. Interestingly, some individuals who experienced early-life EA are resilient against the development of psychiatric illness in adulthood and are believed to possess distinct neurobiology that confer more effective coping mechanisms.

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium.

Study Objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep macro-architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC).

Association Between Sleep Position, Obesity, and Obstructive Sleep Apnea Severity.

Background: This study examines the relationship between obstructive sleep apnea severity, sleep position, and body weight, particularly focusing on the negative impact of sleeping in a supine position combined with being overweight in a population-based sample.

Methods: The Apnea-Hypopnea Index (AHI) was utilized as a marker of OSA severity and sleep position from a standardized overnight polysomnography. Participants were categorized by body mass index (BMI) (kg/m) into normal weight/underweight (<25) and overweight (≥25).

Childhood maltreatment and sleep apnea: Findings from a cross-sectional general population study.

Objective: Cumulative evidence indicates that childhood maltreatment (CM) is associated with sleep disturbances possibly suggesting sleep apnea. However, the relation between CM and objective measures of sleep apnea as determined by polysomnography (PSG) has not yet been assessed.

Methods: Using a cross-sectional design and based on PSG measurements from N = 962 subjects from the SHIP-Trend general population study, we used linear regression models to investigate the relationship between apnea-hypopnea (AHI) and oxygen desaturation index (ODI) and Epworth sleepiness scale (ESS) metrics and the Childhood Trauma Questionnaire (CTQ).

Associations between sleep health and grey matter volume in the UK Biobank cohort ( = 33 356).

As suggested by previous research, sleep health is assumed to be a key determinant of future morbidity and mortality. In line with this, recent studies have found that poor sleep is associated with impaired cognitive function. However, to date, little is known about brain structural abnormalities underlying this association.

Evaluating heart rate variability with 10 second multichannel electrocardiograms in a large population-based sample.

Introduction: Heart rate variability (HRV), defined as the variability of consecutive heart beats, is an important biomarker for dysregulations of the autonomic nervous system (ANS) and is associated with the development, course, and outcome of a variety of mental and physical health problems. While guidelines recommend using 5 min electrocardiograms (ECG), recent studies showed that 10 s might be sufficient for deriving vagal-mediated HRV. However, the validity and applicability of this approach for risk prediction in epidemiological studies is currently unclear to be used.

Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on .

Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation. We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage.

Gene Expression and Its Missense Variant rs3747742 Associate with White Matter Hyperintensity Volume and Alzheimer's Disease-Related Brain Atrophy in the General Population.

Although the common pathology of Alzheimer's disease (AD) and white matter hyperintensities (WMH) is disputed, the gene has been implicated in both conditions: its whole-blood gene expression was associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E () ε4 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany).

The relationship between Alzheimer's-related brain atrophy patterns and sleep macro-architecture.

Introduction: Sleep is increasingly recognized as a major risk factor for neurodegenerative disorders such as Alzheimer's disease (AD).

Methods: Using an magnetic resonance imaging (MRI)-based AD score based on clinical data from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) case-control cohort, we investigated the associations between polysomnography-based sleep macro-architecture and AD-related brain atrophy patterns in 712 pre-symptomatic, healthy subjects from the population-based Study of Health in Pomerania.

Results: We identified a robust inverse association between slow-wave sleep and the AD marker (estimate: -0.

Limited evidence for blood eQTLs in human sexual dimorphism.

Background: The genetic underpinning of sexual dimorphism is very poorly understood. The prevalence of many diseases differs between men and women, which could be in part caused by sex-specific genetic effects. Nevertheless, only a few published genome-wide association studies (GWAS) were performed separately in each sex.

Association Between Obstructive Sleep Apnea and Brain White Matter Hyperintensities in a Population-Based Cohort in Germany.

Importance: Underlying pathomechanisms of brain white matter hyperintensities (WMHs), commonly observed in older individuals and significantly associated with Alzheimer disease and brain aging, have not yet been fully elucidated. One potential contributing factor to WMH burden is chronic obstructive sleep apnea (OSA), a disorder highly prevalent in the general population with readily available treatment options.

Objective: To investigate potential associations between OSA and WMH burden.

Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome.

Comparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs.

Alexithymia is associated with reduced vitamin D levels, but not polymorphisms of the vitamin D binding-protein gene.

Objective: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions, which is associated with various psychiatric disorders, including depression and posttraumatic stress disorder (PTSD). Its pathogenesis is incompletely understood but previous studies suggested that genetic as well as metabolic factors, are involved. However, no results on the role of vitamin D and the polymorphisms rs4588 and rs7041 of the vitamin D binding protein (VDBP) have been published so far.

ENIGMA-Sleep: Challenges, opportunities, and the road map.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols.

Associations and interactions of the serotonin receptor genes 5-HT1A, 5-HT2A, and childhood trauma with alexithymia in two independent general-population samples.

Previous studies suggested that childhood trauma and a disturbed serotonergic neurotransmission are involved in the pathogenesis of alexithymia. Specifically, genetic polymorphisms of the serotonin receptors 5-HT1A and 5-HT2A were found to be associated with alexithymia. However, it is unclear whether these factors show main or interaction effects with childhood trauma on alexithymia.