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

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.

Publication: Nature

L. Peruzzotti-Jametti, C. M. Willis, G. Krzak, R. Hamel, L. Pirvan, R.-B. Ionescu, J. A. Reisz, H. A. Prag, M. E. Garcia-Segura, V. Wu, Y. Xiang, B. Barlas, A. M. Casey, A. M. R. van den Bosch, A. M. Nicaise, L. Roth, G. R. Bates, H. Huang, P. Prasad, A. E. Vincent, C. Frezza, C. Viscomi, G. Balmus, Z. Takats, J. C. Marioni, A. D’Alessandro, M. P. Murphy, I. Mohorianu & S. Pluchino

13 March 2024

Summary

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species.

Publication: Nature

Minna K. Karjalainen, Savita Karthikeyan, Clare Oliver-Williams, Eeva Sliz, Elias Allara, Wing Tung Fung, Praveen Surendran, Weihua Zhang, Pekka Jousilahti, Kati Kristiansson, Veikko Salomaa, Matt Goodwin, David A. Hughes, Michael Boehnke, Lilian Fernandes Silva, Xianyong Yin, Anubha Mahajan, Matt J. Neville, Natalie R. van Zuydam, Renée de Mutsert, Ruifang Li-Gao, Dennis O. Mook-Kanamori, Ayse Demirkan, Jun Liu, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, …Johannes Kettunen

6 March 2024

Summary

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases. Researchers present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. 

Publication: JAC-Antimicrobial Resistance

Nick K Jones, Brian Tom, Constantinos Simillis, John Bennet, Stavros Gourgiotis, Jo Griffin, Helen Blaza, Shuaib Nasser, Stephen Baker, Theodore Gouliouris

16 February 2024

Summary

Being labelled as allergic to penicillin has been associated with an increase in the risk of infection after surgery in a number of studies in USA, Canada and France. This is thought to be due to the use of inferior antibiotic regimens for preventing infection at the time of surgery. We studied a large cohort of patients that had undergone gastrointestinal surgery at Addenbrooke’s Hospital to see if this observation could be generalised to a UK population, where the range of preventative antibiotic regimens in routine use differs significantly. We found no evidence of association between penicillin allergy labels and likelihood of surgical site infection in this cohort, suggesting significant international variation in the impact of penicillin allergy labels on patients.

Publication: The Lancet

Nurulamin M Noor, James C Lee, Simon Bond, Francis Dowling, Biljana Brezina, Kamal V Patel, Tariq Ahmad, Paul J Banim, James W Berrill, Rachel Cooney, Juan De La Revilla Negro, Shanika de Silva, Shahida Din, Dharmaraj Durai, John N Gordon, Prof Peter M Irving, Matthew Johnson, Alexandra J Kent, Klaartje B Kok, Prof Gordon W Moran, Craig Mowat, Pritash Patel, Prof Chris S Probert, Tim Raine, Rebecca Saich, Abigail Seward, Dan Sharpstone, Melissa A Smith, Sreedhar Subramanian, Sara S Upponi, Alan Wiles, Horace R T Williams, Prof Gijs R van den Brink, Prof Séverine Vermeire, Prof Vipul Jairath, Prof Geert R D’Haens, Prof Eoin F McKinney, Paul A Lyons, Prof James O Lindsay, Nicholas A Kennedy, Prof Kenneth G C Smith, Prof Miles Parkes,  

22 February 24

Summary

A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold. Read the full news story.

Publication: The British Journal of Psychiatry

Axel A. S. Laurell, Ashwin V. Venkataraman, Tatjana Schmidt, Marcella Montagnese, Christoph Mueller,
Robert Stewart, Jonathan Lewis, Clare Mundell, Jeremy D. Isaacs, Mani S. Krishnan, Robert Barber, Timothy Rittman and Benjamin R. Underwood

18 January 2024

Summary

Clinical researchers at Cambridgeshire and Peterborough NHS Foundation Trust and South London and Maudsley NHS Foundation Trust have collaborated to model how many patients might receive new treatments for Alzheimer’s disease currently under review.

Using data on eligible patients from both Trusts and scaling up, the team estimate that a maximum of 30,000 people using dementia services around the country would be suitable for these potential treatments and that NHS providers could provide them on a small scale if approved. Read the full news story.

Publication: Lancet Microbe

Francesc Coll, Theodore Gouliouris, Beth Blane, Corin A Yeats, Kathy E Raven, Catherine Ludden, Fahad A Khokhar, Hayley J Wilson, Leah W Roberts, Ewan M Harrison, Carolyne S Horner, Le Thi Hoi, Nguyen Thi Hoa, Nguyen Vu Trung, Nicholas M Brown, Prof Mark A Holmes, Prof Julian Parkhill, P Mili Estee Török, Prof Sharon J Peacock,

11 January 2024

Summary

A team of scientists at the Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Wellcome Sanger Institute and the London School of Hygiene and Tropical Medicine have gone a step forward by establishing the agreement between culture-based laboratory methods and genome sequencing for antibiotic resistance determination in Enterococcus faecium, one of the top 10 bacterial pathogens with the highest mortality burden globally. The team curated a set of over 200 genetic markers that most accurately predict resistance to 12 different, clinically relevant antibiotics in a collection of over 4,000 E. faecium strains. For key antibiotics such as ampicillin, ciprofloxacin, vancomycin and linezolid, the team reported very high diagnostic accuracy, and improved accuracy for the detection of resistance to other antibiotics compared to previous state-of-the-art predictive methods. In addition, the authors implemented the antibiotic resistance predictions on Pathogenwatch

Publication: Nature

M. Fejzo, N. Rocha, I. Cimino, S. M. Lockhart, C. J. Petry, R. G. Kay, K. Burling, P. Barker, A. L. George, N. Yasara, A. Premawardhena, S. Gong, E. Cook, D. Rimmington, K. Rainbow, D. J. Withers, V. Cortessis, P. M. Mullin, K. W. MacGibbon, E. Jin, A. Kam, A. Campbell, O. Polasek, G. Tzoneva, F. M. Gribble, G. S. H. Yeo, B. Y. H. Lam, V. Saudek, I. A. Hughes, K. K. Ong, J. R. B. Perry, A. Sutton Cole, M. Baumgarten, P. Welsh, N. Sattar, G. C. S. Smith, D. S. Charnock-Jones, A. P. Coll, C. L. Meek, S. Mettananda, C. Hayward, N. Mancuso & S. O’Rahilly

Summary

13 December 2023

A Cambridge-led study supported by the NIHR Cambridge BRC has shown why many women experience nausea and vomiting during pregnancy – and why some women become so sick they need to be admitted to hospital. The culprit is a hormone produced by the fetus – a protein known as GDF15. But how sick the mother feels depends on a combination of how much of the hormone is produced by the fetus and how much exposure the mother had to this hormone before becoming pregnant. Read the full news story.

Publication: BJOG

Yasmina Al Ghadban, Yuheng Du, D. Stephen Charnock-Jones, Lana X. Garmire, Gordon C. S. Smith, Ulla Sovio

20 November 2023

Summary

This study identified metabolites from the blood of pregnant mothers that are predictive of spontaneous preterm birth. The results require validation in external populations.

Publication: Nature Microbiology

29 November 2023

Francesca Gaccioli, Katie Stephens, Ulla Sovio, Flora Jessop, Hilary S. Wong, Susanne Lager, Emma Cook, Marcus C. de Goffau, Kirsty Le Doare, Sharon J. Peacock, Julian Parkhill, D. Stephen Charnock-Jones, Gordon C. S. Smith

Summary:

One in 200 newborns is admitted to a neonatal unit with sepsis caused by a bacteria commonly carried by their mothers – much greater than the previous estimate, say Cambridge researchers. The team has developed an ultra-sensitive test capable of better detecting the bacteria, as it is missed in the vast majority of cases. Read the full news story.

Publication: BJOG

Yasmina Al Ghadban, Yuheng Du, D. Stephen Charnock-Jones, Lana X. Garmire, Gordon C. S. Smith, Ulla Sovio

20 November 2023

Summary

This study identified metabolites from the blood of pregnant mothers that are predictive of spontaneous preterm birth. The results require validation in external populations.

Publication: Stem Cell Reports

Maha Al-Thani Mary Goodwin-Trotma Steven Bel Krushangi Pate Lauren K. Flemin Catheline Vilain, Marc Abramowicz, Stuart M. Allan, Tao Wang, M. Zameel Cader, Karen Horsburgh, Tom Van Agtmael, Sanjay Sinha, Hugh S. Markus, Alessandra Granata,

16 November 2023

Summary
Cambridge scientists have grown small blood vessel-like models in the lab and used them to show how damage to the scaffolding that support these vessels can cause them to leak, leading to conditions such as vascular dementia and stroke.

Publication: Journal of Neuroscience

Rong Ye, Frank H. Hezemans, Claire O’Callaghan, Kamen A. Tsvetanov, Catarina Rua, P. Simon Jones, Negin Holland, Maura Malpetti, Alexander G. Murley, Roger A. Barker, Caroline H. Williams-Gray, Trevor W. Robbins, Luca Passamonti and James B. Rowe

5 September 2023

Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals and are linked with worse prognosis, and lack improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system.

Here we test the hypothesis that structural variation of the LC explains response inhibition deficits in PSP and PD. Twenty-four people with idiopathic PD, 14 with PSP-Richardson’s syndrome, and 24 age- and sex-matched controls undertook a stop-signal task and ultrahigh field 7T magnetisation-transfer-weighted imaging of the LC. Parameters of ‘race models’ of go- versus stop-decisions were estimated using hierarchical Bayesian methods to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between LC integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. PSP caused a distinct pattern of abnormalities in inhibitory control with a paradoxically reduced threshold for go responses, but longer non-decision times, and more lapses of attention.

The variation in response inhibition correlated with the variability of LC integrity across participants in both clinical groups. Structural imaging of the LC, coupled with behavioural modelling in parkinsonian disorders, confirms that LC integrity is associated with response inhibition and LC degeneration contributes to neurobehavioural changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimisation of noradrenergic treatment is likely to benefit from stratification according to LC integrity.

Publication: Journal of Internal Medicine

Youngwon Kim, Haeyoon Jang, Mengyao Wang, Qiaoxin Shi, Tessa Strain, Stephen J Sharp, Shiu Lun Au Yeung, Shan Luo, Simon Griffin, Nicholas J. Wareham, Katrien Wijndaele, Soren Brage

23 August 2023

Summary

Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown.