Publications

Publication: Scientific Reports

Tomas I. Gonzales, Kate Westgate, Tessa Strain, Stefanie Hollidge, Justin Jeon, Dirk L. Christensen, Jorgen Jensen, Nicholas J. Wareham & Søren Brage

28 July 2021

Summary

High cardiorespiratory fitness is associated with improved health, but exercise tests to measure fitness can be risky for some people.

Researchers developed a novel method to estimate fitness from lower-risk personalised exercise tests. The validity of the new method outperformed previous methods. The team then applied it to examine associations between fitness and health outcomes in the UK Biobank Study. Again, the new method was better than other approaches: Fitness could be estimated in more study participants, and fitness-to-health relationships were stronger. These results reinforce the importance of cardiorespiratory fitness for human health.

Publication: Neurobiology of Aging

David JWhiteside, P. Simon Jones, Boyd C P Ghosh, Ian Coyle-Gilchrist, Alexander Gerhard, Michele T. Hu, Johannes C Klein, P. Nigel Leigh, Alastair Church, David J Burn, Huw R Morris, James B Rowe, TimothyRittman

16 July 2021

Summary

This study investigated patterns of brain activity at rest in the neurodegenerative disease progressive supranuclear palsy (PSP).

The study found that participants with PSP spend more time than individuals without the disease in certain brain states, meaning their brain activity was less flexible and less efficient than normal. The time spent in these brain states was more apparent in participants who were more severely affected.

The changes in the brain’s activity did not only involve regions of the brain that are most affected by PSP, meaning that effect of the tau protein pathology of PSP has consequences across the whole brain, even where it may appear normal on a scan or have no tau pathology.

Publication: International Journal of Epidemiology

Peige Song, Ananya Gupta, Ian Y Goon, Mehedi Hasan, Sara Mahmood, Rajendra Pradeepa, Samreen Siddiqui, Gary S Frost, Dian Kusuma, Marisa Miraldo, Franco Sassi, Nick J Wareham, Sajjad Ahmed, Ranjit M. Anjana, Soren Brage, Nita G Forouhi, Sujeet Jha, Anuradhani Kasturiratne, Prasad Katulanda, Khadija I Khawaja, Marie Loh, Malay K Mridha, Ananda R Wickremasinghe, Jaspal S Kooner, John C Chambers,

09 July 2021

Summary

Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are leading and closely interlinked global health challenges. The burdens of T2DM and CVD are especially high in South Asia, one of the most populous and the most densely populated regions of the world. Identification of the primary risk factors for T2DM and CVD is central to the development of effective approaches for the prevention and treatment of chronic diseases such as T2DM and CVD. To address this important need, we have established a unique cross-sectional population-based study focused on the South Asian population: the South Asia Biobank (SAB).

Publication: Pediatric Obesity

Laurentya Olga, Inge A. L. P. van Beijsterveldt, Ieuan A. Hughes, David B. Dunger, Ken K. Ong, Anita C. S. Hokken-Koelega, Emanuella De Lucia Rolfe

10 June 2021

Summary

Anthropometry-based equations (included weight, height, body mass index etc.) are commonly used to estimate infant body composition. However, existing equations were designed for newborns or adolescents. We aimed to (a) derive new prediction equations in infancy against air-displacement plethysmography (ADP-PEA Pod) as the criterion, (b) validate the newly developed equations in an independent infant cohort and (c) compare them with published equations (Slaughter-1988, Aris-2013, Catalano-1995).

Publication: Nutrients

Tuck Seng Cheng, Felix R. Day, John R. B. Perry, Jian’an Luan, Claudia Langenberg, Nita G. Forouhi, Nicholas J. Wareham and Ken K. Ong

20 May 2021

Summary

Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid saturated fatty acids with several puberty timing traits in boys and girls.

Publication: Journal of Nutrition

Philip T James, Zakari Ali, Andrew E Armitage, Ana Bonell, Carla Cerami, Hal Drakesmith, Modou Jobe, Kerry S Jones, Zara Liew, Sophie E Moore, Fernanda Morales-Berstein, Helen M Nabwera, Behzad Nadjm, Sant-Rayn Pasricha, Pauline Scheelbeek, Matt J Silver, Megan R Teh, Andrew M Prentice

1 July 2021

Summary

Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19.

Publication: European Journal of Nutrition

Tuck Seng Cheng, Stephen J. Sharp, Soren Brage, Pauline M. Emmett, Nita G. Forouhi & Ken K. Ong

7 July 2021

Summary

Early puberty is associated with adverse health outcomes. To identify potential modifiable factors for puberty timing, we examined the associations of prepubertal childhood macronutrient intakes with puberty timing in boys and girls. The findings suggest habitual total energy intakes in children, and protein intakes in girls, as potential modifiable determinants of puberty timing.

Publication: International Journal of Environmental Research and Public Health

Annie M. Constable, Josie E. Porter, Danielle Benger, Dimitris Vlachopoulos, Alan R. Barker, Sarah A. Moore 3 , Sonja Soininen, Eero A. Haapala, Kate Westgate, Soren Brage, Ricardo R. Agostinete, Romulo A. Fernandes, and Timo A. Lakka

18 May 2021

Summary

Moderate-to-vigorous physical activity (MVPA) positively influences bone mineral content (BMC) in prepubertal children, but it is unknown whether this relationship is partially mediated by free leptin index. The aim of this study was to examine whether the relationship between MVPA and total body less head (TBLH) BMC is mediated or moderated by free leptin index in prepubertal children.

Publication: Nature Communications

William S. Harris, Nathan L. Tintle, Fumiaki Imamura, Frank Qian, Andres V. Ardisson Korat, Matti Marklund, Luc Djoussé, Julie K. Bassett, Pierre-Hugues Carmichael, Yun-Yu Chen, Yoichiro Hirakawa, Leanne K. Küpers, Federica Laguzzi, Maria Lankinen, Rachel A. Murphy, Cécilia Samieri, Mackenzie K. Senn, Peilin Shi, Jyrki K. Virtanen, Ingeborg A. Brouwer, Kuo-Liong Chien, Gudny Eiriksdottir, Nita G. Forouhi, Johanna M. Geleijnse, Graham G. Giles, Vilmundur Gudnason, Catherine Helmer, Allison Hodge, Rebecca Jackson, Kay-Tee Khaw, Markku Laakso, Heidi Lai, Danielle Laurin, Karin Leander, Joan Lindsay, Renata Micha, Jaako Mursu, Toshiharu Ninomiya, Wendy Post, Bruce M. Psaty, Ulf Risérus, Jennifer G. Robinson, Aladdin H. Shadyab, Linda Snetselaar, Aleix Sala-Vila, Yangbo Sun, Lyn M. Steffen, Michael Y. Tsai, Nicholas J. Wareham, Alexis C. Wood, Jason H. Y. Wu, Frank Hu, Qi Sun, David S. Siscovick, Rozenn N. Lemaitre, Dariush Mozaffarian

24 April 2021

Summary

The EPIC-Norfolk Study from the MRC Epidemiology Unit and sixteen other study groups from Europe, the United States, and Asia came together to do research in the framework of the FORCE – Fatty Acids & Outcomes Research – Consortium. In this global collaboration, researchers examined the relationship between markers of fish consumption in the blood and the risk of death from any cause, analysing data from a total of 42,466 study volunteers.

Researchers measured blood levels of ‘omega-3 polyunsaturated fatty acids’, which are molecules circulating in our blood. Fish is typically rich in those markers or ‘omega-3s’. Our body cannot synthesise them, and thus the blood levels of those markers reflect habitual or usual fish consumption.   Our analysis showed  that those showing higher blood levels of omega-3s lived longer than those with lower levels. In other words, those people with relatively low omega-3 levels died prematurely, i.e., all else being equal, they might have lived longer had their blood omega-3 levels been higher.

Publication: Journal of Obesity

Marie W. Lundblad, Bjarne K. Jacobsen, Jonas Johansson, Emanuella De Lucia Rolfe, Sameline Grimsgaard, and Laila A. Hopstock

17 May 2021

Summary

Reference values for visceral adipose tissue (VAT) are needed and it has been advocated that body composition measures depend on both the technique and methods applied, as well as the population of interest.

We aimed to develop reference values for VAT in absolute grams (VATg), percent (VAT%), and as a kilogram-per-meters-squared index (VATindex) for women and men, and investigate potential differences between these measures and their associations with cardiometabolic risk factors (including metabolic syndrome (MetS).

These VAT reference values and thresholds, developed in a sample of adults of Norwegian origin, could be applied to other studies with similar populations using the same DXA device and protocols. The associations between VAT and cardiometabolic risk factors were similar across different measurement units of VAT.

Publication: The American Journal of Clinical Nutrition

Jelisa Gallant, Kathleen Chan, Tim J Green, Frank T Wieringa, Shalem Leemaqz, Rem Ngik, Jeffrey R Measelle, Dare A Baldwin, Mam Borath, Prak Sophonneary, Lisa N Yelland, Daniela Hampel, Setareh Shahab-Ferdows, Lindsay H Allen, Kerry S Jones, Albert Koulman, Damon A Parkington, Sarah R Meadows, Hou Kroeun, Kyly C Whitfield

07 April 2021

Summary

Thiamine (vitamin B1) is essential for normal growth, development and energy metabolism. Thiamine is found in a wide-range of foods and deficiency is not usually a problem with a varied diet. However, in some populations, with diets that consist mostly of thiamine-poor white, polished rice, there may be an increased risk of thiamine deficiency.

The NIHR Cambridge BRC Nutritional Biomarker Laboratory was responsible for the blood analysis of two thiamine biomarkers for a recently published study led by Dr Kyly Whitfield (Mount Saint Vincent University, Canada). The aim of the study was to investigate the amount of supplemental thiamine intake required to optimise breastmilk thiamine concentrations and mother and infant blood thiamine status.

In the study, 335 mothers in rural Cambodia were randomised to one of four daily thiamine supplementation doses (0, 1.2, 2.4, or 10 mg per day) from 2 weeks to 6 months postpartum. At the end of the intervention period, blood samples were collected from mothers and infants, and breastmilk from mothers to estimate the optimal thiamine dose to improve thiamine status.

The results showed that women taking any of the thiamine-containing supplements had significantly higher thiamine content in their milk compared to the placebo group. Both mothers and infants had improved blood thiamine status after supplementation. In the study, a dose of 1.2 mg thiamine/day improved the thiamine status of breastfeeding mothers and their infants, normalising thiamine status, and may reduce the risk of thiamine deficiency and infantile beriberi. We hope the results of this study will inform a future thiamine fortification program in Cambodia, and elsewhere in South and Southeast Asia where thiamine deficiency remains a public health concern.

Publication: Nature

Ekaterina Yonova-Doing, Claudia Calabrese, Aurora Gomez-Duran, Katherine Schon, Wei Wei, Savita Karthikeyan, Patrick F. Chinnery & Joanna M. M. Howson

17 May 2021

Summary

Mitochondrial DNA (mtDNA) variation in common diseases has been underexplored, partly due to a lack of genotype calling and quality-control procedures. Developing an at-scale workflow for mtDNA variant analyses, we show correlations between nuclear and mitochondrial genomic structures within subpopulations of Great Britain and establish a UK Biobank reference atlas of mtDNA–phenotype associations.

Publication: Stroke

Segun Fatumo , Ville Karhunen, Tinashe Chikowore, Toure Sounkou , Brenda Udosen, Chisom Ezenwa, Mariam Nakabuye, Opeyemi Soremekun, Iyas Daghlas, David K. Ryan, Amybel Taylor, Amy M. Mason, Scott M. Damrauer, Marijana Vujkovic, Keith L. Keene, Myriam Fornage, Marjo-Riitta Järvelin, Stephen Burgess, Dipender Gill,

3 June 2021

Summary

Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals

Publication: Proceedings of the National Academy of Sciences (PNAS)

Irene Cimino, Hanna Kim, Y. C. Loraine Tung, Kent Pedersen, Debra Rimmington, John A. Tadross,  Sara N. Kohnke, Ana Neves-Costa, André Barros, Stephanie Joaquim, Don Bennett, Audrey Melvin, Samuel M. Lockhart,  Anthony J. Rostron, Jonathan Scott, Hui Liu,  Keith Burling, Peter Barker, Menna R. Clatworthy, E-Chiang Lee,A. John Simpson, Giles S. H. Yeo, Luís F. Moita, Kendra K. Bence, Sebastian Beck Jørgensen, Anthony P. Coll, Danna M. Breen, and Stephen O’Rahilly

30 June 2021

Summary

Researchers have described a new way that the body senses damage and activates hormones in response to stressful situations – involving the protein GDF15

Publication: Clinical Trials

Estée Török, Benjamin R Underwood, Mark Toshner, Claire Waddington, Emad Sidhom, Katherine Sharrocks, Rachel Bousfield, Charlotte Summers, Caroline Saunders, Zoe McIntyre, Helen Morris, Jo Piper, Gloria Calderon, Sarah Dennis, Tracy Assari, Anita Marguerie de Rotrou, Ashley Shaw, John Bradley, John O’Brien, Robert C Rintoul, Ian Smith, Ed Bullmore, Krishna Chatterjee

22 June 2021

Summary

Researchers describe their experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom.

Researchers encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. These were overcome by setting up a project team that included key members from all three organisations that met at least daily by teleconference.

Publication: Cell Reports

Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova

29 June 2021

One of the key mutations seen in the ‘Alpha variant’ of SARS-CoV-2 – the deletion of two amino acids, H69/V70 – enables the virus to overcome chinks in its armour as it evolves, say an international team of scientists.

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation – the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Researchers led by scientists at the University of Cambridge show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

• Read the press release about this research.

Publication: Science Direct

Setareh Alabaf, Brian Kirkpatrick, Shanquan Chenc, Rudolf N. Cardinal, Emilio Fernandez-Egea

28 June 2021

Summary

Researchers examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms.

Publication: Authorea (pre-print)

Mark Ferris, Rebecca Ferris, Chris Workman, Eoin O’Connor, David A Enoch, Emma Goldesgeyme, Natalie Quinnell, Parth Patel, Jo Wright, Geraldine Martell, Christine Moody, Ashley Shaw, Christopher J.R. Illingworth, Nicholas J. Matheson, Michael P. Weekes

24 June 2021

When Addenbrooke’s Hospital in Cambridge upgraded its face masks for staff working on COVID-19 wards to filtering face piece 3 (FFP3) respirators, it saw a dramatic fall – up to 100% – in hospital-acquired SARS-CoV-2 infections among these staff.

The findings are reported by a team at the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust. The research has not yet been peer-reviewed, but is being released early because of the urgent need to share information relating to the pandemic.

Publication: Annals of Clinical and Translational Neurology

Maura Malpetti, , Negin Holland, P. Simon Jones, Rong Ye, , Thomas E. Cope, Tim D. Fryer, Young T. Hong, George Savulich, Timothy Rittman, Luca Passamonti, Elijah Mak, Franklin I. Aigbirhio, John T. O’Brien, & James B. Rowe

16 June 2021

Summary

Brain cells communicate via special connections called synapses. The loss of these synapses is common and early in dementia. We can now measure the amount of synapses across the brain, in people, with a brain scanning technique called positron emission tomography.

Researchers studied healthy adults who were at risk of developing dementia because of a mutation in a gene called C9orf72. They found that synapse loss was already present many years before symptoms were expected, especially in a part of the brain called the thalamus. Such early pre-symptomatic changes are vital to measure, in order to test preventative treatments to step dementia in people at high genetic risk

Publication: Geriatric Psychiatry

Kathy Y. Liu, Robert Howard, Sube Banerjee, Adelina Comas-Herrera, Joanne Goddard, Martin Knapp, Gill Livingston, Jill Manthorpe, John T. O’Brien, Ross W. Paterson, Louise Robinson, Martin Rossor, James B. Rowe, David J. Sharp, Andrew Sommerlad, Aida Suárez-González, Alistair Burns

16 May 2021

In response to a commissioned research update on dementia during the COVID-19 pandemic, a UK-based working group, comprising dementia researchers from a range of fields and disciplines, aimed to describe the impact of the pandemic on dementia wellbeing and identify priorities for future research.