Insights into genetic variants associated with NASH-fibrosis from metabolite profiling 

Publication: Nature

Alexandra Strauss, Peter Swann, Stacey L. Kigar, Rafailia Christou, Natalia Savinykh Yarkoni, Lorinda Turner, Alexander G. Murley, Leonidas Chouliaras, Noah Shapiro, Nicholas J. Ashton, George Savulich, W. Richard Bevan-Jones, Ajenthan Surendranthan, Kaj Blennow, Henrik Zetterberg, John T. O’Brien, James B. Rowe & Maura Malpetti

29 October 2024

Summary

The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g., microglia), peripheral innate immune cells (e.g., blood monocytes, natural killer cells, and dendritic cells) may also differ in these conditions. However, the characterization of peripheral innate immune cell types across different neurodegenerative diseases remains incomplete. This study aimed to characterize peripheral innate immune profiles using flow cytometry for immunophenotyping of peripheral blood mononuclear cells.

Publication: Journal of Hospital Infection

Rebecca C. Brock, Robert J.B. Goudie, Christine Peters, Rachel Thaxter, Theodore Gouliouris, Christopher J.R. Illingworth, Andrew Conway Morris, Clive B. Beggs, Matthew Butler, Victoria L. Keevil

5 October 2024

Summary

Researchers have been leading the Addenbrookes Air Disinfection Study (AAirDS) looking at whether Air Cleaning Units in hospital wards reduce hospital-acquired infections, particularly COVID-19.

Publication: Brain

Catarina Rua, Betty Raman, Christopher T Rodgers, Virginia F J Newcombe, Anne Manktelow, Doris A Chatfield, Stephen J Sawcer, Joanne G Outtrim, Victoria C Lupson, Emmanuel A Stamatakis, Guy B Williams, William T Clarke, Lin Qiu, Martyn Ezra, Rory McDonald, Stuart Clare, Mark Cassar, Stefan Neubauer, Karen D Ersche, Edward T Bullmore, David K Menon, Kyle Pattinson, James B Rowe 

08 October 2024

Summary

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford and supported by NIHR Cambridge and Oxford BRCs, were able to observe the damaging effects Covid-19 can have on the brain. Read the full news story.

Publication: Sleepmedicine

Aviva Stafford, Sheri Oduola, Sarah Reeve

Published online 10 September 2024

Highlights

• Sleep is minimally documented in severe mental illness (SMI) patient records.
• Recommended sleep interventions (e.g., CBT-I) are rarely delivered in SMI settings.
• Further work is needed to improve sleep assessment and intervention in SMI settings.
• Targeting sleep in SMI patients could significantly improve symptoms and wellbeing.

Publication: Nature Communications

M. Kelemen, J. Danesh, E. Di Angelantonio, M. Inouye, J. O’Sullivan, L. Pennells, T. Roychowdhury, M. J. Sweeting, A. M. Wood, S. Harrison & L. G. Kim,

14 September 2024

Summary

Abdominal aortic aneurysm (AAA) is a serious condition where the abdominal aorta enlarges and can rupture.  AAA usually causes no symptoms; therefore, screening is important. 

AAA has a heritable element of up to 70% multiple genetic variants contribute to the genetic risk. Researchers used a polygenic risk score (PRS), a method that aggregates the propensity for a trait, to capture the genetic risk for AAA. Using a computer simulation model, we explore the possibility of using the PRS to inform the age for AAA screening and compare this to the current strategy in England.

Publication: Social Psychiatry and Psychiatric Epidemiology

Kaminska J, Hodgekins J, Lewis JR, Cardinal RN, Oduola S

09 September 2024

Summary

This study examined de-identified NHS data about people having a first episode of psychosis, and looked at how the psychosis began (abruptly or slowly), how long it went untreated, and factors including rural or urban residence. Among such people, some factors differed between rural and urban settings, e.g. employment and living with family. A slow onset of psychosis was associated with a longer time untreated, but rural/urban differences in “time untreated” were not found.

Publication: Nature Communications

Samantha Ip, Teri-Louise North, Fatemeh Torabi, Yangfan Li, Hoda Abbasizanjani, Ashley Akbari, Elsie Horne, Rachel Denholm, Spencer Keene, Spiros Denaxas, Amitava Banerjee, Kamlesh Khunti, Cathie Sudlow, William N. Whiteley, Jonathan A. C. Sterne, Angela M. Wood, Venexia Walker, the CVD-COVID-UK/COVID-IMPACT Consortium & the Longitudinal Health and Wellbeing COVID-19 National Core Study

31 July 2024

Summary

A new study has found heart attacks and strokes were lower after COVID-19 vaccination than before or without vaccination.

Publication: American Journal of Human Genetics

Thomas Vanderstichele, Katie L. Burnham, Niek de Klein, Michael Inouye, Dirk S. Paul, Emma E. Davenport et al

24 July 2024

Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors.

We found that while individual misexpression events occur rarely, in aggregate they were found in almost all samples and a third of inactive protein-coding genes. Using 2,821 paired whole-genome and RNA sequencing samples, we identified that misexpression events are enriched in cis for rare structural variants. We established putative mechanisms through which a subset of SVs lead to gene misexpression, including transcriptional readthrough, transcript fusions, and gene inversion. Overall, we develop misexpression as a type of transcriptomic outlier analysis and extend our understanding of the variety of mechanisms by which genetic variants can influence gene expression.

Publication: eClinicaMedicine

Liz Yuanxi Lee j, Delshad Vaghari j, Michael C. Burkhart, Peter Tino, Marcella Montagnese, Zhuoyu Li,
Katharina Zühlsdorff, Joseph Giorgio, Guy Williams, Eddie Chong, Christopher Chen, Benjamin R. Underwood, Timothy Rittman, Zoe Kourtzi

12 July 2024

Summary

Cambridge researchers have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease. Read the full press release.

Publication: BMC Medicine

Chen S, Underwood BR, Cardinal RN, Chen X, Chen S, Amin J, Jin H, Mueller C, Yan LL, Brayne C, Kuper H

26 June 2024

Summary

This was an analysis of pre-existing data from the English Longitudinal Study of Ageing, examining changes over time in risk factors for dementia that have the potential to be altered (such as hypertension, obesity, hearing loss, and social isolation).

Publication: Magnetic Resonance Materials in Physics, Biology and Medicine

Jonathan Birchall, Ines Horvat-Menih, Joshua Kaggie, Arnold Benjamin, Martin Graves, Ian Wilkinson, Ferdia Gallagher, Mary McLean

1 June 2024

Summary

We estimated the sodium content and relaxation of organs within the abdomen of healthy human volunteers using magnetic resonance imaging (MRI). Existing techniques for measuring sodium content are non-specific or require an invasive biopsy. Clinical translation of sodium content monitoring may aid in diagnosis of disease such as cancer, chronic kidney disease and hypertension at earlier stages, and more regular monitoring may help to evaluate efficacy of treatment.

Publication: BJPsych

London SR, Chen S, Sidhom E, Lewis JR, Wolverson E, Cardinal RN, Roalf D, Mueller C, Underwood BR

13 May 2024

Summary

People diagnosed with dementia are often diagnosed in memory clinics and then discharged back to their GP. Some later need intensive mental health support (e.g. crisis teams, or inpatient admission) but others do not. This study shows that it’s possible to predict who will and who won’t, with useful accuracy, based on information collected routinely at the time of initial diagnosis.

Publication: The Lancet regional health - Europe

Isaac Allen, Hend Hassan, Walburga Yvonne Joko-Fru, Catherine Huntley, Lucy Loong, Tameera Rahman, Bethany Torr, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Margreet Lüchtenborg, Joanna Pethick, Katrina Lavelle, Fiona McRonald, Diana Eccles, Eva J.A Morris, Steven Hardy, Clare Turnbull,
Marc Tischkowitz, Paul Pharoah, Antonis C. Antoniou,

25 April 2024

Summary

Survivors of breast cancer are at significantly higher risk of developing second cancers, including endometrial and ovarian cancer for women and prostate cancer for men, according to new research studying data from almost 600,000 NHS England patients. Read the full news item.

Publication: BJPsych

Emilio Fernandez-Egea, Shanquan Chen, Estela Sangüesa, Patricia Gassó, Marjan Biria, James Plaistow, Isaac Jarratt-Barnham, Nuria Segarra, Sergi Mas, Maria-Pilar Ribate, Cristina B García, Naomi A Fineberg, Yulia Worbe, Rudolf N Cardinal, Trevor W Robbins

Summary

This study looked at a group of people treated with clozapine for schizophrenia, examining obsessive-compulsive symptoms (OCS). For some, genetic variants were examined. OCS were common in this group (37.9%). Analysis suggested that both psychosis and clozapine may drive aspects of OCS.

Publication: Nature Neuroscience

Richard Dear, Konrad Wagstyl, Jakob Seidlitz, Ross D. Markello, Aurina Arnatkevičiūtė, Kevin M. Anderson, Richard A. I. Bethlehem, Lifespan Brain Chart Consortium, Armin Raznahan, Edward T. Bullmore & Petra E. Vértes

22 April 2024

Summary

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development.

Publication: PNAS

Sofia C. Orellana Richard A. I. Bethlehem, Ivan L. Simpson-Kent and Edward T. Bullmore

9 April 2024

Summary

A new study has found that childhood maltreatment can have an impact into adulthood because of how it effects an individual’s risk of poor physical health and traumatic experiences many years later

Publication: Nature Genetics

Yajie Zhao, Maria Chukanova, Katherine A. Kentistou, Zammy Fairhurst-Hunter, Anna Maria Siegert, Raina Y. Jia, Georgina K. C. Dowsett, Eugene J. Gardner, Katherine Lawler, Felix R. Day, Lena R. Kaisinger, Yi-Chun Loraine Tung, Brian Yee Hong Lam, Hsiao-Jou Cortina Chen, Quanli Wang, Jaime Berumen-Campos, Pablo Kuri-Morales, Roberto Tapia-Conyer, Jesus Alegre-Diaz, Inês Barroso, Jonathan Emberson, Jason M. Torres, Rory Collins, Danish Saleheen, Katherine R. Smith, Dirk S. Paul, Florian Merkle, I. Sadaf Farooqi, Nick J. Wareham, Slavé Petrovski, Stephen O’Rahilly, Ken K. Ong, Giles S. H. Yeo & John R. B. Perry

4 April 2024

Summary

A study has identified genetic variants in two genes that have some of the largest impacts on obesity risk discovered to date.

The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.

Publication: Nature aging

Yang Liu, Scott C. Ritchie, Shu Mei Teo, Matti O. Ruuskanen, Oleg Kambur, Qiyun Zhu, Jon Sanders, Yoshiki Vázquez-Baeza, Karin Verspoor, Pekka Jousilahti, Leo Lahti, Teemu Niiranen, Veikko Salomaa, Aki S. Havulinna, Rob Knight, Guillaume Méric & Michael Inouye

25 March 2024

Summary

Researchers have shown that risk scores based on our genes and gut bacteria can improve the prediction of diseases such as type 2 diabetes and prostate cancer over traditional risk factors alone.

Publication: Nature Communications

Genevieve I. Cezard, Rachel E. Denholm, Rochelle Knight, Yinghui Wei, Lucy Teece, Renin Toms, Harriet J. Forbes, Alex J. Walker, Louis Fisher, Jon Massey, Lisa E. M. Hopcroft, Elsie M. F. Horne, Kurt Taylor, Tom Palmer, Marwa Al Arab, Jose Ignacio Cuitun Coronado, Samantha H. Y. Ip, Simon Davy, Iain Dillingham, Sebastian Bacon, Amir Mehrkar, Caroline E. Morton, Felix Greaves, Catherine Hyams, George Davey Smith, John Macleod, Nishi Chaturvedi, Ben Goldacre, William N. Whiteley, Angela M. Wood, Jonathan A. C. Sterne & Venexia Walker On behalf of the Longitudinal Health and Wellbeing and Data and Connectivity UK COVID-19 National Core Studies, CONVALESCENCE study and the OpenSAFELY collaborative

11 March 2024

Summary

Researchers looked at cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. They studied distinct groups: a ‘pre-vaccination’ cohort in the wild-type/Alpha variant eras and ‘vaccinated’ and ‘unvaccinated’ cohorts in the Delta variant era.

They showed that people with COVID-19 are more likely to develop cardiovascular diseases in the first 4 weeks after diagnosis compared to people without COVID-19. The effects can be long lasting. The excess risk of cardiovascular disease remains elevated up to 6 months after COVID-19 diagnosis but it reduces over time. People who had COVID-19 in the wild-type/Alpha variant eras (before vaccination became available to them) are at higher risk of cardiovascular events up to two years after COVID-19.

Publication: Pediatrics

Grace H. Kromm; Hilary Patankar; Shubang Nagalotimath; Hilary Wong, Topun Austin,

5 March 2024

Summary

Babies who suffer brain injury before, during or shortly after birth because of lack of oxygen to the brain may face longer-term socioemotional and psychological complications, research supported by the NIHR Cambridge BRC has shown. Read the news article.