Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

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.

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Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy

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.

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Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease

Publication: Cell Reports Medicine

Ruth Hanssen, Chiara Auwerx, Maarja Jõeloo, Sadaf Farooqi, Alexandre Reymond, Katherine Lawler

15 August 2023


New approaches are needed to treat people whose obesity and type 2 diabetes (T2D) are driven by specific mechanisms. We investigate a deletion on chromosome 16p11.2 (breakpoint 2–3 [BP2–3]) encompassing SH2B1, a mediator of leptin and insulin signaling. Phenome-wide association scans in the UK (N = 502,399) and Estonian (N = 208,360) biobanks show that deletion carriers have increased body mass index (BMI; p = 1.3 × 10−10) and increased rates of T2D. Compared with BMI-matched controls, deletion carriers have an earlier onset of T2D, with poorer glycemic control despite higher medication usage. Cystatin C, a biomarker of kidney function, is significantly elevated in deletion carriers, suggesting increased risk of renal impairment. In a Mendelian randomization study, decreased SH2B1 expression increases T2D risk (p = 8.1 × 10−6). We conclude that people with 16p11.2 BP2–3 deletions have early, complex obesity and T2D and may benefit from therapies that enhance leptin and insulin signaling.

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Accelerated waning of the humoral response to COVID-19 vaccines in obesity

Publication: Nature Medicine

Agatha A. van der Klaauw, Emily C. Horner, Pehuén Pereyra-Gerber, Utkarsh Agrawal, William S. Foster, Sarah Spencer, Bensi Vergese, Miriam Smith, Elana Henning, Isobel D. Ramsay, Jack A. Smith, Stephane M. Guillaume, Hayley J. Sharpe, Iain M. Hay, Sam Thompson, Silvia Innocentin, Lucy H. Booth, Chris Robertson, Colin McCowan, Steven Kerr, Thomas E. Mulroney, Martin J. O’Reilly, Thevinya P. Gurugama, Lihinya P. Gurugama, Maria A. Rust, Alex Ferreira, Soraya Ebrahimi, Lourdes Ceron-Gutierrez, Jacopo Scotucci, Barbara Kronsteiner, Susanna J. Dunachie, Paul Klenerman, PITCH Consortium, Adrian J. Park, Francesco Rubino, Abigail A. Lamikanra, Hannah Stark, Nathalie Kingston, Lise Estcourt, Heli Harvala, David J. Roberts, Rainer Doffinger, Michelle A. Linterman, Nicholas J. Matheson, Aziz Sheikh, I. Sadaf Farooqi & James E. D. Thaventhiran

11 May 2023

Summary

Clinical trials have shown that COVID-19 vaccines are highly effective at reducing symptoms, hospitalisation and deaths caused by the virus, including for people with obesity. Previous studies have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear. Read the news story.

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Factors Associated with Significant Weight Loss in Hospitalised Patients with COVID-19: A Retrospective Cohort Study in a Large Teaching Hospital

Publication: Nutrients

Dimitra Zannidi, Pinal S. Patel, Eleni Leventea, Jessica Paciepnik,  Frances Dobson,  Caroline Heyes, Robert J. B. Goudie,  Linda M. Oude Griep,  Jacobus Preller, and Lynsey N. Spillman, 

8 October 2022


Summary

Previous research has shown that people hospitalised with COVID-19 are at risk of weight loss and malnutrition. This study looked at patients who experienced weight loss of 10% or more during their hospital admission to Cambridge University Hospitals NHS with COVID-19 during the first wave of the pandemic. Weight loss of 10% or more is considered a large amount to lose as it increases the chance of someone becoming more poorly and not surviving. Therefore, preventing weight loss may help patients to survive and recover. The study looked at risk factors for weight loss to help better recognise the patients that need more support to prevent weight loss. 

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Association of Accelerometer‐Measured Sedentary Accumulation Patterns With Incident Cardiovascular Disease, Cancer, and All‐Cause Mortality

Publication: Journal of the American Heart Association

Paddy C. Dempsey, Tessa Strain, Elisabeth A. H. Winkler, Kate Westgate, Kirsten L. Rennie, Nicholas J. Wareham, Soren Brage, Katrien Wijndaele

26 April 2022


Summary

Emerging evidence suggests accruing sedentary behavior in relatively more prolonged periods may convey additional cardiometabolic risks, but few studies have examined prospective outcomes. Researchers examined the association of sedentary behavior accumulation patterns with incident cardiovascular disease, cancer, and all‐cause mortality.

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Data Resource Profile: United Kingdom National Diet and Nutrition Survey Rolling Programme (2008-19)

Publication: International Journal of Epidemiology

Michelle Venables, Caireen Roberts, Kerry Jones, Anila Farooq, Albert Koulman, Nick Wareham, Polly Page

28 May 2022


Since 2008, the Government in the United Kingdom has funded a large, annual survey called the National Diet and Nutrition Survey Rolling Programme (NDNS RP) to collect detailed information from people on the foods they are eating and their nutritional health.

The survey is used to monitor how well the UK population is doing in terms of dietary guidelines and inform the development of new nutrition policies. It is also used to monitor chemical exposure risk to protect food safety. In this NIHR Cambridge BRC paper, the authors have provided easy access to comprehensive information about the NDNS for the academic and wider public health community.

The paper describes the data collected in the first 11 years of the NDNS RP, how it has been used, and demonstrates the scope of publicly available data. The authors present an overview of survey methods to collect and analyse the data.

Between 2008 and 2019, 7999 adults and 7656 children completed food diaries; 4181 adults and 2014 children had a blood sample taken; 3246 adults and 2318 children gave a urine sample and 419 adults and 352 children had their energy expenditure measured. The authors explain how NDNS survey reports and data provide information on the foods, calories and nutrients such as fat, sugar and vitamins consumed by the UK population, and how Government use these data in public health campaigns such as the Change4Life, 5 A DAY and sugar reduction and folate fortification policies.

They also highlight that many other institutions and individuals use the survey including international organisations like the World Health Organisation. Reports are published regularly by Government: https://www.gov.uk/government/collections/national-diet-and-nutrition-survey. Anonymised individual data can be accessed from the Data Service and stored blood and urine samples are available for further research via the NDNS Bioresource.

The NDNS RP provides a unique and valuable publicly available resource for the UK Government, researchers, health professionals and others looking to understand and improve population health and nutrition.

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Effects of Limiting Recreational Screen Media Use on Physical Activity and Sleep in Families With Children: A Cluster Randomized Clinical Trial

Publication: JAMA Pediatrics

Soren Brage

23 May 2022


This was a randomised controlled trial examining the effect of restricting screen use in 89 families living in Denmark. Children in intervention families reduced their objectively measured sedentary time by 45 min/day, which was significantly more than the 1 min/day increase observed in children from control families.

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Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis

Publication: JAMA Psychiatry

Soren Brage

13 April 2022


Depression is a disorder characterised by persistent sadness and a lack of interest or pleasure in previously enjoyable activities. It is the leading cause of mental health-related disease burden, affecting approximately 1 in 20 adults worldwide. Reviews of the scientific evidence have shown that depression may be prevented by physical activity, but the benefits at different levels of activity are unclear.

The aim of this study was to combine results from previously published studies to estimate the association between different levels of physical activity and depression. We searched medical databases for studies including at least 3000 adults published up until 12th November 2020. The studies had to report the risk of developing depression for at least three different levels of physical activity.

We included studies irrespective of how they measured physical activity. We standardised these measures to a common format so that the published results could be analysed together and make sense on the same physical activity scale. We estimated what proportion of depression cases would have been avoided if all adults in the studies met the current physical activity recommendations. We included 15 studies with 191,130 participants and found that even small doses of physical activity appeared to substantially lower risks of depression. Adults meeting physical activity recommendations (equivalent to 2.5 hrs/week of brisk walking) had 25% lower risk of depression compared with adults reporting no physical activity.

Our findings suggested that most benefits occurred when moving from no activity to at least some, and that only minor additional benefits were achieved by further increasing activity levels. Approximately 1 in 9 cases of depression might have been prevented if everybody in the population was active at the level of current health recommendations.

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Physical activity attenuates but does not eliminate coronary heart disease risk amongst adults with risk factors: EPIC-CVD case-cohort study

Publication: European Journal of Preventive Cardiology

Nita Forouhi, Soren Brage, Nick Wareham

11 April 2022


This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.

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