Childhood allergy and anxiety/depression in early adulthood: A longitudinal study in the ALSPAC birth cohort.

Background: Allergic disease and common mental disorders frequently co-occur. However, little is known about the longitudinal impact of childhood allergy on the subsequent risk of developing anxiety or depression, and the possible biological mechanisms for this.

Methods: We performed longitudinal analyses of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.

Brain multi-omic Mendelian randomisation to identify novel drug targets for gliomagenesis.

Background: Genetic variants associated with molecular traits that are also associated with liability to glioma can provide causal evidence for the identification and prioritisation of drug targets.

Methods: We performed comprehensive two-sample Mendelian randomisation (Wald ratio and/or IVW) and colocalisation analyses of molecular traits on glioma. Instrumentable traits (QTLs P < 5 × 10-8) were identified amongst 11 985 gene expression measures, 13 285 splicing isoforms and 10 198 protein abundance measures, derived from 15 brain regions.

Imputation provides an opportunity to study filaggrin ( ) null mutations in large population cohorts that lack bespoke genotyping.

Background: Null mutations within the filaggrin ( ) gene are established genetic risk factors for atopic dermatitis. Studies of have typically used sequencing or bespoke genotyping. Large-scale population cohorts with genome-wide imputed data offer powerful genetic analysis opportunities, but bespoke genotyping is often not feasible in such studies.

Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank.

Background: Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

Methods: We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; n=51 929; n=39 980) and subsequent arterial ischemic stroke (AIS; n=45 120; n=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank.

Genetic landscape of atopic dermatitis.

Purpose Of Review: This review summarizes recent advances in identifying genetic risk factors for atopic dermatitis and how these genetic associations are being used to explore the causal relationships between atopic dermatitis and potential risk factors and downstream outcomes.

Recent Findings: A recent large-scale GWAS meta-analysis has identified 91 genetic loci associated with atopic dermatitis. Rare variant studies have also identified new gain-of-function or loss-of-function variants implicated in atopic dermatitis, particularly for FLG and STAT6/JAK1 .

From GWASs toward Mechanistic Understanding with Case Studies in Dermatogenetics.

Many human skin diseases result from the complex interplay of genetic and environmental mechanisms that are largely unknown. GWASs have yielded insight into the genetic aspect of complex disease by highlighting regions of the genome or specific genetic variants associated with disease. Leveraging this information to identify causal genes and cell types will provide insight into fundamental biology, inform diagnostics, and aid drug discovery.

Protein identification for stroke progression via Mendelian Randomization in Million Veteran Program and UK Biobank.

Background: Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

Methods: We performed genome-wide association studies (GWAS) for subsequent major adverse cardiovascular events (MACE) (N=51,929, N=39,980) and subsequent arterial ischemic stroke (AIS) N=45,120, N=46,789) after first incident stroke within the Million Veteran Program and UK Biobank.

Investigation of genetic determinants of cognitive change in later life.

Cognitive decline is a major health concern and identification of genes that may serve as drug targets to slow decline is important to adequately support an aging population. Whilst genetic studies of cross-sectional cognition have been carried out, cognitive change is less well-understood. Here, using data from the TOMMORROW trial, we investigate genetic associations with cognitive change in a cognitively normal older cohort.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).

Strategies to investigate and mitigate collider bias in genetic and Mendelian randomisation studies of disease progression.

Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors that influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as "index event") bias since the disease progression phenotype can only be observed for individuals who have the disease.

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.

Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index.

Objectives: Observational analyses suggest that high bone mineral density (BMD) is a risk factor for osteoarthritis (OA); it is unclear whether this represents a causal effect or shared aetiology and whether these relationships are body mass index (BMI)-independent. We performed bidirectional Mendelian randomization (MR) to uncover the causal pathways between BMD, BMI and OA.

Methods: One-sample (1S)MR estimates were generated by two-stage least-squares regression.

Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort.

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, , herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, , Theiler's virus, , and SAG1 protein domain, a surface antigen of measured for greater precision.

Investigating the causal relationship between allergic disease and mental health.

Background: Observational studies have reported an association between allergic disease and mental health, but a causal relationship has not been established. Here, we use Mendelian randomization (MR) to investigate a possible causal relationship between atopic disease and mental health phenotypes.

Methods: The observational relationship between allergic disease and mental health was investigated in UK Biobank.

Triangulating Molecular Evidence to Prioritize Candidate Causal Genes at Established Atopic Dermatitis Loci.

GWASs for atopic dermatitis have identified 25 reproducible loci. We attempt to prioritize the candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for atopic dermatitis etiology, including expression, protein, and DNA methylation quantitative trait loci datasets in the skin or immune-relevant tissues, which were tested for overlap with GWAS signals.

Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.

Background: Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis).

The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study.

Objective: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape.

Methods: Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.

Mendelian randomization provides evidence for a causal effect of higher serum IGF-1 concentration on risk of hip and knee osteoarthritis.

Objectives: How insulin-like growth factor-1 (IGF-1) is related to OA is not well understood. We determined relationships between IGF-1 and hospital-diagnosed hand, hip and knee OA in UK Biobank, using Mendelian randomization (MR) to determine causality.

Methods: Serum IGF-1 was assessed by chemiluminescent immunoassay.

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10) with left-handedness and 7 associated with ambidexterity.