Comprehensive evaluation of smoking exposures and their interactions on DNA methylation.

Background: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS).

Methods: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C).

Associations of childhood-to-adulthood body size trajectories and genetic susceptibility with the risks of osteoarthritis: a population-based cohort study of UK Biobank data.

Background: Large adulthood body size was associated with increased risk of osteoarthritis. We aimed to examine the association between body size trajectories from childhood to adulthood and potential interactions with genetic susceptibility on osteoarthritis risk.

Methods: We included participants from the UK Biobank aged 38-73 years in 2006-10.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Voluntary risk mitigation behaviour can reduce impact of SARS-CoV-2: a real-time modelling study of the January 2022 Omicron wave in England.

Background: Predicting the likely size of future SARS-CoV-2 waves is necessary for public health planning. In England, voluntary "plan B" mitigation measures were introduced in December 2021 including increased home working and face coverings in shops but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown.

Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2.

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269).

Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic.

Background: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK).

Methods: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20.

Epigenetic Regulation of Associates With Myocardial Infarction and Platelet Function.

Background: DNA hypomethylation at the (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease.

Youth use of e-liquid flavours-a systematic review exploring patterns of use of e-liquid flavours and associations with continued vaping, tobacco smoking uptake or cessation.

Background And Aims: There is concern that young people may be attracted to e-liquid flavours, prompting long-term vaping in naive users and potentially subsequent tobacco smoking. We aimed to review the use of e-liquid flavours by young people and describe associations with uptake or cessation of both regular vaping and tobacco smoking, adverse effects and subjective experiences.

Design: Systematic review, including interventional, observational and qualitative studies reporting on the use of e-cigarette flavours by young people (aged < 18 years).

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project.

Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data.

The genetic impact of an Ebola outbreak on a wild gorilla population.

Background: Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate.

Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study.

Background: The diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD).

Methods And Findings: Using data from The Health Improvement Network (THIN) in the United Kingdom (2000-2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490).

Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow waves and spindles in healthy young adults.

The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.

Variation of microRNA expression in the human placenta driven by population identity and sex of the newborn.

Background: Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts.

The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease.

Objective: This study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.

Methods: BMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI-driven cytokines on risk of obesity-related diseases.

DNA methylation signature of passive smoke exposure is less pronounced than active smoking: The Understanding Society study.

Introduction: The extent of the biological impact of passive smoke exposure is unclear. We sought to investigate the association between passive smoke exposure and DNA methylation, which could serve as a biomarker of health risk.

Materials And Methods: We derived passive smoke exposure from self-reported questionnaire data among smoking and non-smoking partners of participants enrolled in the UK Household Longitudinal Study 'Understanding Society' (n=769).

Genome-wide associations of human gut microbiome variation and implications for causal inference analyses.

Recent population-based and clinical studies have identified a range of factors associated with human gut microbiome variation. Murine quantitative trait loci, human twin studies and microbiome genome-wide association studies have provided evidence for genetic contributions to microbiome composition. Despite this, there is still poor overlap in genetic association across human studies.

An Independent Locus Upstream of Controls Variation in the Shade of the Bay Coat Colour in Horses.

Novel coat colour phenotypes often emerge during domestication, and there is strong evidence of genetic selection for the two main genes that control base coat colour in horses- and . These genes direct the type of pigment produced, red pheomelanin () or black eumelanin (), as well as the relative concentration and the temporal-spatial distribution of melanin pigment deposits in the skin and hair coat. Here, we describe a genome-wide association study (GWAS) to identify novel genic regions involved in the determination of the shade of bay.

Targeted conservation genetics of the endangered chimpanzee.

Populations of the common chimpanzee (Pan troglodytes) are in an impending risk of going extinct in the wild as a consequence of damaging anthropogenic impact on their natural habitat and illegal pet and bushmeat trade. Conservation management programmes for the chimpanzee have been established outside their natural range (ex situ), and chimpanzees from these programmes could potentially be used to supplement future conservation initiatives in the wild (in situ). However, these programmes have often suffered from inadequate information about the geographical origin and subspecies ancestry of the founders.

Common variation at 16p11.2 is associated with glycosuria in pregnancy: findings from a genome-wide association study in European women.

Glycosuria is a condition where glucose is detected in urine at higher concentrations than normal (i.e. not detectable).