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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe

Publication: European Heart Journal

SCORE2 working group and ESC Cardiovascular risk collaboration

13 June 2021

Summary

The researchers analysed data from nearly 700,000 mainly middle-aged participants in 45 large-scale studies to develop risk prediction models (SCORE2) tailored for use in European countries.

The participants did not have previous history of CVD at the outset and 30,000 had a CVD event (heart attack or stroke) during the first 10 years of follow up.

These risk models were then statistically adapted or ‘recalibrated’ to more accurately estimate CVD risk for contemporary populations in four European risk regions, using data on population-specific CVD incidence rates and risk factor values from 10.8 million individuals. Read the full story

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Cardiovascular risk factors and lifestyle behaviours in relation to longevity: a Mendelian randomization study

Publication: Journal of Internal Medicine

S. van Oort, J. W. J. Beulens, A. J. van Ballegooijen, S. Burges,s S. C. Larsson

26 October 2020

Summary

The American Heart Association introduced the Life’s Simple 7 initiative to improve cardiovascular health by modifying cardiovascular risk factors and lifestyle behaviours. It is unclear whether these risk factors are causally associated with longevity.

This study aimed to investigate causal associations of Life’s Simple 7 modifiable risk factors, as well as sleep and education, with longevity using the two‐sample Mendelian randomization design.

Risk factors associated with a lower odds of longevity included the following: genetic liability to type 2 diabetes, genetically predicted systolic and diastolic blood pressure, body mass index, low‐density lipoprotein cholesterol and smoking initiation. Genetically increased high‐density lipoprotein cholesterol and educational level were associated with a higher odds of longevity. Fasting glucose and other lifestyle factors were not significantly associated with longevity.

Most of the Life’s Simple 7 modifiable risk factors are causally related to longevity. Prevention strategies should focus on modifying these risk factors and reducing education inequalities to improve cardiovascular health and longevity.

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Survey of CAMHS clinicians about their experience of remote working: brief report

Publication: BJPsych Open

Bhardwaj A, Moore A, Cardinal RN, Bradley C, Cross L, Ford TJ

13 January 2021

The Covid-19 crisis necessitated rapid adoption of remote consultations across National Health Service (NHS) child and adolescent mental health services (CAMHS).

This study aimed to understand practitioners’ experiences of rapid implementation of remote consultations across CAMHS in one NHS trust in the east of England.

Data were collected through a brief questionnaire documenting clinicians’ experiences following remote delivery of services. The questionnaire began before ‘lockdown’ and focused on 102 assessment consultations as part of a planned move to virtual assessment.

As the roll-out of remote consultations was extended at lockdown, the researchers extended the questionnaire to include all remote clinical contacts (n = 202).

Despite high levels of initial concern, clinicians’ reports were positive overall; importantly, however, their experiences varied by team. When restrictions on face-to-face working are lifted, a blended approach of remote and face-to-face service delivery is recommended to optimise access and capacity while retaining effective and safe care.

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Birth weight, family history of diabetes and diabetes onset in schizophrenia

Publication: BMJ Open Diabetes Research & Care

Fernández-Egea E, Walker R, Ziauddeen H, Cardinal RN, Bullmore ET

28 January 2020

The prevalence of diabetes in schizophrenia is twice that in the general population, but there are few reliable predictors of which individuals will develop glucose dysregulation.

This research tested if abnormal birth weight (either too low or too high) and parental diabetes, both variables that can be ascertained in the clinic, can predict diabetes onset in patients with schizophrenia.

Researchers looked at electronic records of a cohort of 190 clozapine-treated patients (37% treated for more than 20 years) and Cox regression survival analysis (with any type of glucose dysregulation as the event) to account for differences in length of treatment before the event and age at clozapine treatment initiation.

Age at clozapine initiation, family history of diabetes and birth weight were significant predictors of glucose dysregulation onset, while gender was not.

Among individuals with 10 years of follow-up, 80% of those with both abnormal birth weight and a family history of diabetes developed diabetes compared with 56% with only abnormal birth weight, 40% with only a family history of diabetes and 20% in those with neither.

Since 48% of cases had at least one risk factor and 6% had both risk factors, there is a substantial proportion of patients for whom preventive strategies could be implemented.

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Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach

Publication: The Lancet Psychiatry

Varun Warrier, Alex S F Kwong, Mannan Luo, Shareefa Dalvie, Jazz Croft, Hannah M Sallis, et al.

16 March 2021

Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene–environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, the researchers aimed to delineate the sources of gene–environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health.

They did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank, Psychiatric Genomics Consortium, Avon Longitudinal Study of Parents and Children, Adolescent Brain Cognitive Development Study and Generation R.

Family-based and population-based polygenic score analyses were done to elucidate gene–environment correlation mechanisms. The team used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions.

This meta-analysis of genome-wide association studies identified 14 independent loci associated with childhood maltreatment. The researchers identified high genetic overlap among different maltreatment operationalisations, subtypes, and reporting methods.

Within-family analyses provided some support for active and reactive gene–environment correlation but did not show the absence of passive gene–environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration).

Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment.

Family-based analyses point to a role of active and reactive gene–environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. This study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects.

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Improving reporting standards for polygenic scores in risk prediction studies

Publication: Nature

Hannah Wand, Samuel A. Lambert, Cecelia Tamburro, Michael A. Iacocca, Jack W. O’Sullivan, Catherine Sillari, Iftikhar J. Kullo, Robb Rowley, Jacqueline S. Dron, Deanna Brockman, Eric Venner, Mark I. McCarthy, Antonis C. Antoniou, Douglas F. Easton, Robert A. Hegele, Amit V. Khera, Nilanjan Chatterjee, Charles Kooperberg, Karen Edwards, Katherine Vlessis, Kim Kinnear, John N. Danesh, et al

10 March 2021

Summary

This research is a perspective piece that provides a framework to promote the validity, transparency, and reproducibility of polygenic risk scores (PRS) by encouraging authors to detail the study population, statistical methods, and potential clinical utility of a published score.

Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics.

However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, the researchers present the Polygenic Risk Score Reporting Standards (PRS-RS), in which they update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field.

Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications.

The researchers encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.

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The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation;

Publication: Nature Genetics

Samuel A. Lambert, Laurent Gil, Simon Jupp, Scott C. Ritchie, Yu Xu, Annalisa Buniello, Aoife McMahon, Gad Abraham, Michael Chapman, Helen Parkinson, John Danesh, Jacqueline A. L. MacArthur & Michael Inouye

10 March 2021

Summary

Researchers have led a report describing an important new set of reporting guidelines and an international open science database for polygenic risk scores, which are powerful genomic tools being increasingly used to predict disease outcomes and traits.

The Polygenic Score (PGS) Catalog is an open resource of published scores (including variants, alleles and weights) and consistently curated metadata required for reproducibility and independent applications.

The PGS Catalog has capabilities for user deposition, expert curation and programmatic access, thus providing the community with a platform for PGS dissemination, research and translation.

It promotes PGS reproducibility by providing a venue to annotate and distribute scores according to current exemplar reporting standards. As such, it allows users to reuse and evaluate PGSs, to firmly establish their predictive ability and facilitate further investigations of clinical utility.

  • Visit the PGS Catalog website: https://www.PGSCatalog.org

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Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Publication: International Journal of Epidemiology

Aurora Perez-Cornago , Francesca L Crowe, Paul N Appleby, Kathryn E Bradbury, Angela M Wood, Marianne Uhre Jakobsen, Laura Johnson, Carlotta Sacerdote, Marinka Steur, Elisabete Weiderpass, Anne Mette L Würtz, Tilman Kühn, Verena Katzke, Antonia Trichopoulou, Anna Karakatsani, Carlo La Vecchia, Giovanna Masala, Rosario Tumino, Salvatore Panico, Ivonne Sluijs, Guri Skeie, Liher Imaz, Dafina Petrova, J Ramón Quirós, Sandra Milena Colorado Yohar, Paula Jakszyn, Olle Melander, Emily Sonestedt, Jonas Andersson, Maria Wennberg, Dagfinn Aune, Elio Riboli, Matthias B Schulze, Emanuele di Angelantonio, Nicholas J Wareham, John Danesh, Nita G Forouhi, Adam S Butterworth, Timothy J Key

3 March 2021

Summary

Epidemiological evidence indicates that diets rich in plant foods are associated with a moderately lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre.

This study found that higher intakes of fruit and vegetables combined, total fruit, bananas, nuts and seeds, total fibre, fruit and vegetable combined fibre and fruit fibre are associated with a lower risk of IHD, of small magnitude.

To the best of the researchers’ knowledge, this is the largest prospective study looking at major plant foods, their subtype, and dietary fibre in relation to IHD risk including incident IHD cases and death from IHD.

As with other observational studies, the associations reported may be subject to residual confounding, and whether these small associations are causal remains unclear.

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Are Mendelian randomization investigations immune from bias due to reverse causation?

Publication: European Journal of Epidemiology

Stephen Burgess, Sonja A Swanson & Jeremy A Labrecque

21 February 2021

Mendelian randomization uses genetic variants as instrumental variables to make causal inferences about the effect of a risk factor on an outcome. If a genetic variant satisfies the instrumental variable assumptions for the given risk factor and outcome, then an association between the genetic variant and the outcome implies the risk factor affects the outcome in some individuals at some point in the life-course.

Combining the instrumental variable assumptions with further assumptions and precise specification of the outcome (including specifying a time period for the outcome) allows valid testing of a more specific causal hypothesis and/or valid estimation of global or local, and point or period average causal effects.

In this short manuscript, the researchers discuss three ways in which Mendelian randomization analyses may be susceptible to bias due to reverse causation. They conclude that while the analyses offer some protection against biases, they are not totally immune from the phenomenon; and that researchers should consider carefully whether their findings could be explained by genetic variants having a primary association with the outcome, and how previous versions of an outcome can impact the stated risk factor.

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Modifiable Lifestyle Factors and Risk of Stroke: A Mendelian Randomization Analysis

Publication: Stroke AHA

Eric L. Harshfield, Marios K. Georgakis, Rainer Malik, Martin Dichgans, Hugh S. Markus

4 February 2021

Summary

Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data.

Here the research team evaluated whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischemic stroke and its subtypes and hemorrhagic stroke.

They performed 2-sample and multivariable Mendelian randomization to assess the causal effect of 12 lifestyle factors on risk of stroke and whether these effects are independent.

Genetically predicted years of education was inversely associated with ischemic, large artery, and small vessel stroke, and intracerebral hemorrhage.

Genetically predicted smoking, body mass index, and waist-hip ratio were associated with ischemic and large artery stroke. The effects of education, body mass index, and smoking on ischemic stroke were independent.

These findings support the hypothesis that reduced education and increased smoking and obesity increase risk of ischemic, large artery, and small vessel stroke, suggesting that lifestyle modifications addressing these risk factors will reduce stroke risk.

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