Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder.

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree ( ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder.

Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults: Implications for Primary Prevention.

Background: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes.

Objectives: This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.

Coding variants in and increase risk of atrial fibrillation.

Most sequence variants identified hitherto in genome-wide association studies (GWAS) of atrial fibrillation are common, non-coding variants associated with risk through unknown mechanisms. We performed a meta-analysis of GWAS of atrial fibrillation among 29,502 cases and 767,760 controls from Iceland and the UK Biobank with follow-up in samples from Norway and the US, focusing on low-frequency coding and splice variants aiming to identify causal genes. We observe associations with one missense (OR = 1.

Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction.

Aims: To investigate whether improved survival from non-ST-elevation myocardial infarction (NSTEMI), according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge.

Methods And Results: National cohort study (n = 389 507 patients, n = 232 hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates.

Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.

Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy.

Background: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells.

Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: progress, pitfalls, and potential.

In the past few years, the use of specific cell types derived from induced pluripotent stem cells (iPSCs) has developed into a powerful approach to investigate the cellular pathophysiology of numerous diseases. Despite advances in therapy, heart disease continues to be one of the leading causes of death in the developed world. A major difficulty in unravelling the underlying cellular processes of heart disease is the extremely limited availability of viable human cardiac cells reflecting the pathological phenotype of the disease at various stages.

Machine learning models in electronic health records can outperform conventional survival models for predicting patient mortality in coronary artery disease.

Prognostic modelling is important in clinical practice and epidemiology for patient management and research. Electronic health records (EHR) provide large quantities of data for such models, but conventional epidemiological approaches require significant researcher time to implement. Expert selection of variables, fine-tuning of variable transformations and interactions, and imputing missing values are time-consuming and could bias subsequent analysis, particularly given that missingness in EHR is both high, and may carry meaning.

Cardio-oncology: an overview on outpatient management and future developments.

Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients.

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity.

Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.

Background: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.

Results: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts.

The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics.

Background: There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants.

Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants.

Background: UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.

Aims: An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.

Method: An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability.

Organic solvents and MS susceptibility: Interaction with MS risk HLA genes.

Objective: We hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes.

Methods: Using a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression.

Acute kidney injury in the UK: a replication cohort study of the variation across three regional populations.

Objectives: A rapid growth in the reported rates of acute kidney injury (AKI) has led to calls for greater attention and greater resources for improving care. However, the reported incidence of AKI also varies more than tenfold between previous studies. Some of this variation is likely to stem from methodological heterogeneity.

'Who does this patient belong to?' boundary work and the re/making of (NSTEMI) heart attack patients.

This ethnography within ten English and Welsh hospitals explores the significance of boundary work and the impacts of this work on the quality of care experienced by heart attack patients who have suspected non-ST segment elevation myocardial infarction (NSTEMI) /non-ST elevation acute coronary syndrome. Beginning with the initial identification and prioritisation of patients, boundary work informed negotiations over responsibility for patients, their transfer and admission to different wards, and their access to specific domains in order to receive diagnostic tests and treatment. In order to navigate boundaries successfully and for their clinical needs to be more easily recognised by staff, a patient needed to become a stable boundary object.

Algorithms used in telemonitoring programmes for patients with chronic heart failure: A systematic review.

Introduction: Non-invasive telemonitoring programmes detecting deterioration of heart failure are increasingly used in heart failure care.

Aim: The aim of this study was to compare different monitoring algorithms used in non-invasive telemonitoring programmes for patients with chronic heart failure.

Methods: We performed a systematic literature review in MEDLINE (PubMed) and Embase to identify published reports on non-invasive telemonitoring programmes in patients with heart failure aged over 18 years.

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction.

Background: Beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction. There is uncertainty whether these treatments are beneficial for people with heart failure with preserved ejection fraction and a comprehensive review of the evidence is required.

Objectives: To assess the effects of beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction.

Prescription patterns of angiotensin-converting enzyme inhibitors for various indications: A UK population-based study.

Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed for several cardiovascular indications. This study investigated patterns of ACEI use for various indications.

Methods: A descriptive, retrospective population-based study was conducted using data from the UK Clinical Practice Research Datalink.

CogStack - experiences of deploying integrated information retrieval and extraction services in a large National Health Service Foundation Trust hospital.

Background: Traditional health information systems are generally devised to support clinical data collection at the point of care. However, as the significance of the modern information economy expands in scope and permeates the healthcare domain, there is an increasing urgency for healthcare organisations to offer information systems that address the expectations of clinicians, researchers and the business intelligence community alike. Amongst other emergent requirements, the principal unmet need might be defined as the 3R principle (right data, right place, right time) to address deficiencies in organisational data flow while retaining the strict information governance policies that apply within the UK National Health Service (NHS).

Identifying patients with asthma-chronic obstructive pulmonary disease overlap syndrome using latent class analysis of electronic health record data: a study protocol.

Asthma and chronic obstructive pulmonary disease (COPD) are two common different clinical diagnoses with overlapping clinical features. Both conditions have been increasingly studied using electronic health records (EHR). Asthma-COPD overlap syndrome (ACOS) is an emerging concept where clinical features from both conditions co-exist, and for which, however, there is no consensus definition.