You are here: / / / Population and Quantitative Science /

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Publication: Nature Genetics

Praveen Surendran, Joanna M. M. Howson et al

23 November 2020

Increased blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and related disability worldwide. Identifying biological pathways associated with blood pressure is important to understand the aetiology of CVD.

In this study involving collaborators from across the globe, and participants from diverse ancestries, researchers investigated whether genetic variants that a small proportion of people carry have an impact on blood pressure regulation and more readily implicate the genes underlying blood pressure regulation.

They identified 87 such genetic variants influencing blood pressure regulation that only a small proportion of people carry. In addition to identifying novel candidate genes associated with blood pressure, they showed a potential link between foetal development and an inverse relationship between systolic and diastolic blood pressure with stroke.

As shown in this study, a complex outcome like blood pressure requires large sample sizes to detect genetic variation associated with blood pressure that are rare in humans; studies to date have mainly looked at genetic variants that are carried by many people and therefore have very small effects on blood pressure regulation.

This study contributes to a significant improvement in researchers’ understanding of key genes controlling a risk factor like BP so they can better understand complex diseases like CVD and help identify new blood pressure therapies.

View publication

Accuracy of UK Rapid Test Consortium (UK-RTC) “AbC-19 Rapid Test” for detection of previous SARS-CoV-2 infection in key workers: test accuracy study

Publication: BMJ

Ranya Mulchandani, Hayley E Jones, Sian Taylor-Phillips, Justin Shute, Keith Perry, Shabnam Jamarani, Tim Brooks, Andre Charlett, Matthew Hickman, Isabel Oliver, Stephen Kaptoge, John Danesh, Emanuele Di Angelantonio, Anthony E Ades, David H Wyllie, 

11 November 2020

Summary:

The accuracy of a COVID-19 test is lower than previously believed. Testing nearly 5,000 samples found some results were giving false positives.

View publication

Investigation of risk of dementia diagnosis and death in patients in older people’s secondary care mental health services

Publication: International Journal of Geriatric Psychiatry

Kershenbaum A, Cardinal RN, Chen S, Underwood B, Seyedsalehi A, Lewis JR, Rubinsztein JS

4 November 2020

Previous studies have shown increased rates of death and dementia in older people in specific serious mental illnesses (SMI) such as bipolar disorder or depression.

In this study researchers examined the rates of death and dementia in older people referred into a secondary care psychiatric service across a range of SMIs, using an anonymised dataset across 6 consecutive years with 28,340 patients aged 65 years and older from a single secondary care psychiatric trust in the United Kingdom.

They identified deaths and incident dementia in patients with bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders. They compared mortality and dementia rates between these diagnostic groups and in different treatment settings, and also examined mortality rates and dementia rates compared with general population rates.

Patients with schizophrenia showed the highest hazard rate for death compared to other groups with SMIs. Survival was reduced in patients referred to liaison psychiatry services. There were no significant differences between the SMI groups in terms of rates of dementia. However, risks of death and dementia were significantly increased compared to the general population; and older adults referred into an old age psychiatry service showed higher rates of dementia and death than those reported for the general population.

View publication

Distinguishing between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) using mental health records: a classification approach

Publication: ACL Anthology

Wang Z, Ive J, Moylett S, Mueller C, Cardinal RN, Velupillai S, O’Brien J, Stewart R

1 November 2020

While Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia following Alzheimer’s Disease (AD), it is difficult to distinguish from AD.

Here the researchers propose a method for DLB detection by using mental health record (MHR) documents from a (3-month) period before a patient has been diagnosed with DLB or AD. The objective is to develop a model that could be clinically useful to differentiate between DLB and AD across datasets from different healthcare institutions.

The researchers cast this as a classification task using Convolutional Neural Network (CNN), an efficient neural model for text classification. They experiment with different representation models, and explore the features that contribute to model performances.

In addition, they apply temperature scaling, a simple but efficient model calibration method, to produce more reliable predictions. They believe the proposed method has important potential for clinical applications using routine healthcare records, and for generalising to other relevant clinical record datasets.

To the best of the team’s knowledge, this is the first attempt to distinguish DLB from AD using mental health records, and to improve the reliability of DLB predictions.

View publication

The early impact of COVID-19 on mental health and community physical health services and their patients’ mortality in Cambridgeshire and Peterborough, UK

Publication: Journal of Psychiatric Research

Chen S, Jones PB, Underwood BR, Moore A, Bullmore ET, Banerjee S, Osimo EF, Deakin JB, Hatfield CF, Thompson FJ, Artingstall JD, Slann MP, Lewis JR, Cardinal RN

22 September 2020

COVID-19 has affected social interaction and healthcare worldwide.

Here researchers examined changes in presentations and referrals to the primary provider of mental health and community health services in Cambridgeshire and Peterborough, UK (population ~0·86 million), plus service activity and deaths.

They conducted interrupted time series analyses with respect to the time of UK “lockdown”, which was shortly before the peak of COVID-19 infections in this area, and examined changes in standardized mortality ratio for those with and without severe mental illness (SMI).

Referrals and presentations to nearly all mental and physical health services dropped at lockdown, with evidence for changes in both supply (service provision) and demand (help-seeking).

This was followed by an increase in demand for some services. This pattern was seen for all major forms of presentation to liaison psychiatry services, except for eating disorders, for which there was no evidence of change.

Inpatient numbers fell, but new detentions under the Mental Health Act were unchanged. Many services shifted from face-to-face to remote contacts. Excess mortality was primarily in the over-70s. There was a much greater increase in mortality for patients with SMI, which was not explained by ethnicity.

In conclusion, the research showed that COVID-19 has been associated with a system-wide drop in the use of mental health services, with some subsequent return in activity. “Supply” changes may have reduced access to mental health services for some. “Demand” changes may reflect a genuine reduction of need or a lack of help-seeking with pent-up demand. There has been a disproportionate increase in death among those with SMI during the pandemic.

View publication

Causes of death in clozapine-treated patients in a catchment area: a 10-year retrospective case-control study

Publication: European Neuropsychopharmacology

Rose E, Chen S, Turrion C, Jenkins C, Cardinal RN, Fernández-Egea E

17 September 2020

Approximately one-third of patients presenting with a first episode of psychosis need long-term support, but there is a limited understanding of the sociodemographic or biological factors that predict this outcome. ]

Researchers used electronic health records from a naturalistic cohort of consecutive patients referred to an early intervention in psychosis service to address this question.

They extracted data on demographic (age, sex, ethnicity and marital status), immune and metabolic factors at baseline, and subsequent need for long-term secondary (specialist) psychiatric care.

Of 749 patients with outcome data available, 447 (60%) had a good outcome and were discharged to primary care, while 302 (40%) required follow-up by secondary mental health services indicating a worse outcome.

The need for ongoing secondary mental healthcare was associated with high triglyceride levels, a low basophil:lymphocyte ratio, and a high monocyte count at baseline.

In conclusion, the research provides evidence that triglyceride levels and several blood cell counts measured at presentation may be clinically useful markers of long-term prognosis for first episode psychosis in clinical settings. These findings will require replication.

View publication

Sleep duration and risk of overall and 22 site-specific cancers: A Mendelian randomization study

Publication: International Journal of Cancer

Olga E. Titova, Karl Michaëlsson, Mathew Vithayathil, Amy M. Mason, Siddhartha Kar, Stephen Burgess, Susanna C. Larsson

7 September 2020

Studies of sleep duration in relation to the risk of site‐specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. In this study researchers aimed to investigate the potential causal associations of sleep duration with overall and site‐specific cancers using the Mendelian randomization (MR) design.

The researchers concluded that this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site‐specific cancers. The suggestive associations of short‐ or long‐sleep duration with certain cancers merit further investigation in other large MR studies.

View publication

Effectively Measuring Exercise-related Variations in T1ρ and T2 Relaxation Times of Healthy Articular Cartilage

Publication: Journal of Magnetic Resonance Imaging

Dimitri A. Kessler, James W. MacKay, Scott McDonald, Stephen McDonnell, Andrew J. Grainger, Alexandra R. Roberts, Robert L. Janiczek, Martin J. Graves, Joshua D. Kaggie, Fiona J. Gilbert

The researchers wanted to further understanding of the biomechanical properties of articular cartilage in our knee joints. By combining quantitative magnetic resonance imaging (MRI) and sophisticated 3D surface analysis methods of articular cartilage they were able to determine changes in cartilage microstructure following a mild, 5-minute stepping exercise in young, healthy individuals.

The team determined that our quantitative MRI methods are sensitive to changes of different compositional characteristics of articular cartilage such as changes in its water content or macromolecular structure following the stepping exercise. While previous studies have shown that changes in cartilage morphology (thickness, volume) recovers almost fully in about 45–90 minutes, they showed that the compositional changes induced by the exercise do not recover within an hour following cessation.

This is important because measuring the responses of cartilage to dynamic joint loading may present a way of determining cartilage health state as well as differences in healthy and diseased cartilage. With the exercise performed in this study being short and of limited duration, it could be extended for use in patients with early‐stage knee joint disease and minimal accompanying pain. As exercise is recommended as a form of conservative management of joint disease-related symptoms, the study provides an initial interpretation of short-term changes that occur in cartilage microstructure in response to exercise.

View publication

The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries

Publication: European Heart Journal

Tammy Y N Tong, Paul N Appleby, Timothy J Key, Christina C Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Verena Katzke, Tilman Kühn, Heiner Boeing, Anna Karakatsani, Eleni Peppa, Antonia Trichopoulou, Elisabete Weiderpass, Giovanna Masala, Sara Grioni, Salvatore Panico, Rosario Tumino, Jolanda M A Boer, W M Monique Verschuren, J Ramón Quirós, Antonio Agudo, Miguel Rodríguez-Barranco, Liher Imaz, María-Dolores Chirlaque, Conchi Moreno-Iribas, Gunnar Engström, Emily Sonestedt, Marcus Lind, Julia Otten, Kay-Tee Khaw, Dagfinn Aune, Elio Riboli, Nicholas J Wareham, Fumiaki Imamura, Nita G Forouhi, Emanuele di Angelantonio, Angela M Wood, Adam S Butterworth, Aurora Perez-Cornago

24 February 2020

Summary: 

This research looked at more than 418,000 people in nine European countries who were recruited to the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000. Researchers found that while higher intakes of fruit, vegetables, fibre, milk, cheese or yoghurt were each linked to a lower risk of ischaemic stroke, there was no significant association with a lower risk of haemorrhagic stroke.

As the study is observational, it cannot show that the foods studied cause an increase or decrease in risk of ischaemic or haemorrhagic stroke, only that they are associated with different risks.

View publication

Probabilistic reversal learning under acute tryptophan depletion in healthy humans: a conventional analysis

Publication: Journal of Psychopharmacology

Kanen JW, Arntz FE, Yellowlees R, Cardinal RN, Price A, Christmas DM, Sahakian BJ, Apergis-Schoute AM, Robbins TW

18 February 2020

The involvement of serotonin in responses to negative feedback is well established. Acute serotonin reuptake inhibition has enhanced sensitivity to negative feedback (SNF), modelled by behaviour in probabilistic reversal learning (PRL) paradigms. Whilst experiments employing acute tryptophan depletion (ATD) in humans, to reduce serotonin synthesis, have shown no clear effect on SNF, sample sizes have been small.

The researchers studied a large sample of healthy volunteers, male and female, and found ATD had no effect on core behavioural measures in PRL.

These results indicate that ATD effects can differ from other manipulations of serotonin expected to have a parallel or opposing action.

View publication

The NIHR Cambridge BRC is part of the NIHR and hosted by Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge. We are at the heart of the Cambridge Biomedical Campus, Europe’s largest health research area.

Bluesky

Contact Us

Cambridge Biomedical Research Centre
Box 277
Hills Road
Cambridge
CB2 0QQ

Tel: 01223 348490

Useful Links

About Us
Research
Governance Structure
Partners
Publications
PPIE in Research
News/Events
Vacancies
Accessibility
Privacy

cambridgebrc NIHR Cambridge Biomedical Research Centre @cambridgebrc ·
8 Jan

The Cambridge-led IVORY trial has shown that targeting the immune system, by giving a low-dose of aldesleukin, could prevent future heart attacks by nearly 8%.

Learn more about the study >>https://bit.ly/4aLzW6Q

@CUH_NHS @Cambridge_Uni @NIHRresearch @RoyalPapworth

Reply on Twitter 2009304033052266815 Retweet on Twitter 2009304033052266815 Like on Twitter 2009304033052266815 1 Twitter 2009304033052266815
Retweet on Twitter NIHR Cambridge Biomedical Research Centre Retweeted
themilnerinst Milner Therapeutics Institute @themilnerinst ·
6 Jan

📣 The Milner Consortium Call returns with its sixth call for research proposals. Academic researchers – join our Q&A webinar to learn more and ask questions about the Call!

🗓️ 22 Jan ⏰ 10am 📍 Online

🔗 Register: https://ow.ly/5PMb50XCIuF

🔗 More info: http://www.milner.cam.ac.uk/consortiumcall/

Reply on Twitter 2008448511176511797 Retweet on Twitter 2008448511176511797 3 Like on Twitter 2008448511176511797 3 Twitter 2008448511176511797
cambridgebrc NIHR Cambridge Biomedical Research Centre @cambridgebrc ·
5 Jan

👉 Want to help shape a future trial focused on preventing falls in older people?
👉 Are you an older adult and/or family member/carer? 👉 Free on Wed 21st Jan 2026 at 13.30 for an online group?
👉 Contact James Piercy - james@brainhrc.org
@CUH_NHS @NIHRBrainHRC @Cambridge_Uni

Reply on Twitter 2008222023550726191 Retweet on Twitter 2008222023550726191 Like on Twitter 2008222023550726191 Twitter 2008222023550726191
cambridgebrc NIHR Cambridge Biomedical Research Centre @cambridgebrc ·
31 Dec

🎉Wishing everyone a very Happy New Year!🎉
Thinking of making a #NewYearsResolution?
Are you interested in giving feedback on the #research we do?
Live in the #EastOfEngland?
Then why not join our Patient & Public Involvement Panel >> https://bit.ly/3LlRX1c
@CUH_NHS

Reply on Twitter 2006354596873265413 Retweet on Twitter 2006354596873265413 Like on Twitter 2006354596873265413 2 Twitter 2006354596873265413
cambridgebrc NIHR Cambridge Biomedical Research Centre @cambridgebrc ·
24 Dec

Merry Christmas and a happy #NewYear from the #NIHR #Cambridge BRC!!
#Thankyou to all our amazing staff, everyone who has supported us and all those who took part in #research this year!
@CUH_NHS @Cambridge_Uni @NIHRresearch

Reply on Twitter 2003783374734066150 Retweet on Twitter 2003783374734066150 Like on Twitter 2003783374734066150 4 Twitter 2003783374734066150
cambridgebrc NIHR Cambridge Biomedical Research Centre @cambridgebrc ·
22 Dec

🥳 As 2025 draws to a close, we’ve put together a snapshot of some of our key research stories over the year.
🥳 We’d like to thank everyone who took part in, or contributed to our research over 2025!
To learn more >>
@CUH_NHS @Cambridge_Uni @NIHRresearch

Reply on Twitter 2003053625208344860 Retweet on Twitter 2003053625208344860 1 Like on Twitter 2003053625208344860 5 Twitter 2003053625208344860
View more Tweets
© Copyright - NIHR Cambridge Biomedical Research Centre 2026