DNA methylation-based predictors of metabolic traits in Scottish and Singaporean cohorts.

Exploring the molecular correlates of metabolic health measures may identify their shared and unique biological processes and pathways. Molecular proxies of these traits may also provide a more objective approach to their measurement. Here, DNA methylation (DNAm) data were used in epigenome-wide association studies (EWASs) and for training epigenetic scores (EpiScores) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio, and blood-based measures of glucose, high-density lipoprotein cholesterol, and total cholesterol in >17,000 volunteers from the Generation Scotland (GS) cohort.

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes.

Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.

Lifetime brain atrophy estimated from a single MRI: measurement characteristics and genome-wide correlates.

A measure of lifetime brain atrophy (LBA) obtained from a single magnetic resonance imaging (MRI) scan could be an attractive candidate to boost statistical power in uncovering novel genetic signals and mechanisms of neurodegeneration. We analysed data from five young and old adult cohorts (MRi-Share, Human Connectome Project, UK Biobank, Generation Scotland Subsample, and Lothian Birth Cohort 1936 [LBC1936]) to test the validity and utility of LBA inferred from cross-sectional MRI data, i.e.

Antibiotic prescribing intensity and community UTI resistance: a cross-sectional ecological study.

Background: Antibiotic overuse is associated with antimicrobial resistance (AMR). It is unclear whether community AMR is driven by overall antibiotic use or by high levels of repeated (intense) use by individual patients.

Aim: To determine the association between high antibiotic prescribing intensity (all antibiotic prescriptions; any indication), and rates of UTI resistance among patients within small communities.

The Relationship Between Anxiety, Depression and Cognitive Functioning in Older Adults: An Exploratory Cross-Sectional Analysis of Wave 1 Lothian Birth Cohort 1936 Data.

Objectives: To explore the strength of the association between cognitive functioning and depression and anxiety in older people without dementia.

Methods: An exploratory, cross-sectional analysis of Wave 1 (2004-2007) data from the Lothian Birth Cohort 1936 dataset. Three subgroups were based on Hospital Anxiety and Depression Scale (HADS) subscales: no probable anxiety or depression (N = 592), probable anxiety no depression (N = 122), probable depression with/without anxiety (depression) (N = 30).

Sex-Dependent Effects of Cardiometabolic Health and on Brain Age: A Longitudinal Cohort Study.

Background And Objectives: The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored.

Impact of the COVID-19 pandemic on electronic referrals to rapid access clinics for suspected breast, lung and prostate cancers in Ireland.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted cancer services worldwide. We examined the effect of the first three pandemic waves on the number of electronic (e)-referrals to rapid access clinics (RACs) for breast, lung and prostate cancer in Ireland.

Methods: This study used a retrospective, repeated cross-sectional design.

From lab to life: assessing the impact of real-world interactions on the operation of rapid serial visual presentation-based brain-computer interfaces.

Brain-computer interfaces (BCI) have been extensively researched in controlled lab settings where the P300 event-related potential (ERP), elicited in the rapid serial visual presentation (RSVP) paradigm, has shown promising potential. However, deploying BCIs outside of laboratory settings is challenging due to the presence of contaminating artifacts that often occur as a result of activities such as talking, head movements, and body movements. These artifacts can severely contaminate the measured EEG signals and consequently impede detection of the P300 ERP.

Co-designing a recruitment strategy for lung cancer screening in high-risk individuals: protocol for a mixed-methods study.

Background: Lung cancer is a significant cause of cancer-related mortality globally, with early detection through screening critical to improving patient outcomes. However, recruiting high-risk individuals, particularly in deprived populations, for screening remains a considerable challenge. This study aims to co-design a targeted recruitment strategy for lung cancer screening, tailored to the specific needs and experiences of high-risk individuals, in collaboration with a Patient and Public Involvement (PPI) panel and expert stakeholders in Ireland.

Methylome-wide studies of six metabolic traits.

Exploring the molecular correlates of metabolic health measures may identify the shared and unique biological processes and pathways that they track. Here, we performed epigenome-wide association studies (EWASs) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio (WHR), and blood-based measures of glucose, high-density lipoprotein (HDL) cholesterol, and total cholesterol. We considered blood-based DNA methylation (DNAm) from >750,000 CpG sites in over 17,000 volunteers from the Generation Scotland (GS) cohort.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Introduction: Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer susceptibility for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD susceptibility, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability.

Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health.

Background: Epigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum of DNA methylation (DNAm) levels at CpG sites are predictive of protein levels. Here, we examine 84 previously published protein EpiScores as possible biomarkers of cross-sectional and longitudinal measures of general cognitive function and brain health, and incident dementia across three independent cohorts.

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules.

Protocol for Establishing a Stakeholder Group for Primary Care Research into Cancer Using a Modified 7P Framework and an e-Delphi Process.

Introduction: Currently, no group specifically supports and coordinates primary care focused cancer research in Ireland. The aim of this project is to establish an inclusive stakeholder group for primary care focused cancer research in Ireland, to coordinate research efforts and build capacity in researchers and institutions.

Methods: We will convene a stakeholder group, recruiting individuals with personal and professional experience of cancer care in a community setting.

Genome-wide association study of preserved ratio impaired spirometry (PRISm).

Background: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV) <80% predicted and FEV/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer risk for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD risk, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability.

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.