̽��ֱ�� of Cambridge - Medical Research Council (MRC) Epidemiology Unit

Young adults generally more active after starting work, but sleep less – unless working from home

cjb250 — Tue, 28 Jan 2025 00:01:41 +0000

̽��ֱ��increase in physical activity was mainly seen in those doing semi-routine occupations such as bus driving or hairdressing, and routine occupations such as cleaning or waiting, or technical jobs. There was little change seen among people entering managerial or professional occupations.

People who work from home saw a decrease in levels of physical activity – though their sleep levels did not change when they started work.

Young adulthood – ages 16 to 30 years – is an important time in terms of health. Although we are typically at our peak physical health, it is also a time when many risk factors for long term diseases such as heart disease, type 2 diabetes and cancer begin to develop.

Health guidelines recommend young adults get between seven and nine hours of sleep a night, engage in 150 minutes or more of moderate physical activity per week, and consume at least five portions of fruit and vegetables per day.

Young adulthood is also the time when most people start work, which changes their daily routines and activities, resources such as time and money, and social and physical environments – all of which affect health behaviours and health in later life.

To quantify the impact that starting work has on health-related behaviours, a team led by researchers at the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge examined repeated data taken over time from more than 3,000 participants in the UK Household Longitudinal Study. All the participants were aged 16–30 years and started work for the first time between 2015 and 2023.

̽��ֱ��results are published today in the International Journal of Behavioral Nutrition and Physical Activity.

Dr Eleanor Winpenny, who was based at the ̽��ֱ�� of Cambridge when she carried out the work, but is now at Imperial College London, said: “We know about physical activity and sleep patterns among young people while they’re at school, but very little about what happens when they start work. Given the impact that work can have on our lives – and the lasting impacts this can have on our health – it’s important to try and understand what happens at this transition.”

̽��ֱ��analysis showed that when people started work, their physical activity increased by an amount equivalent to around 28 min of moderate activity (such as cycling) per day on average – but then decreased each year after starting work by around 7 min per day.

̽��ֱ��biggest increase was among males – up by an equivalent of around 45 min of moderate activity per day compared to an increase of around 16 min for females. People who did not have a university degree also showed a greater increase in physical activity compared to those with a university degree – equivalent to around a 42 min increase of moderate physical activity per day compared to 15 min per day.

Working from home, however, appeared to be associated with an initial decrease in physical activity, equivalent to around 32 min of moderate activity per day.

When young adults started work, the amount of time they slept per night dropped immediately by almost 10 minutes and remained stable at this level over time; however, people without a degree showed a continuing decrease of about 3 minutes of sleep per night each year after starting work, while those with a degree slowly increased back to their pre-work sleep levels.

There was little change in the amount of fruit and vegetables consumed after starting work.

Alena Oxenham, from the MRC Epidemiology Unit, said: “Beginning work can have a profound impact on our lifestyles and on behaviours that might make a difference to our health, if not immediately then later in life.

“Although we found that people tend to do more physical activity when they begin work, which is good news, these are averages, and some people – particularly those who work from home and, to a lesser degree, those with office-based jobs – may do less.

“If we want to stay healthy throughout our lives, we need to remember that keeping active is an important way of helping us achieve this goal. Those working at home might want to consider incorporating physical activity into their day, for example by going for a walk before or after work, or during a lunch break.”

Dr Winpenny added: “Workplaces provide an opportunity to create environments and cultures that support healthier diets, more physical activity and better sleep for young adults. This could result in healthier employees and fewer sick days in the immediate term, but also have long term benefits, helping prevent health issues in later life.”

̽��ֱ��research was funded by the MRC and the National Institute for Health and Care Research.

Reference
Oxenham, AF, et al. New job, new habits? A multilevel interrupted time series analysis of changes in diet, physical activity and sleep among young adults starting work for the first time. International Journal of Behavioral Nutrition and Physical Activity; 28 Jan 2025; DOI: 10.1186/s12966-024-01682-8

When young adults start working, the amount of daily physical activity they do increases sharply, only to fall away again over the next few years, while the amount of sleep they get falls slightly, according to new research led by scientists at the ̽��ֱ�� of Cambridge.

If we want to stay healthy throughout our lives, we need to remember that keeping active is an important way of helping us achieve this goal

Alena Oxenham

Roman Koester

Cyclist in London

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Children switch to walking and cycling to school after introduction of London’s Ultra-Low Emission Zone

cjb250 — Wed, 04 Sep 2024 23:01:29 +0000

Car travel contributes to air pollution, a major cause of heart and lung diseases including asthma attacks. Beyond this, it limits children's opportunities for physical activity, hindering their development and mental health, and increasing their risk of obesity and chronic illnesses.

Despite UK guidelines recommending a daily average of 60 minutes of moderate-to-vigorous physical activity for school-aged children and adolescents, less than half (45%) of children aged 5-16 met these levels in 2021. One in three children aged 10-11 in the UK are overweight or obese.

In April 2019, London introduced the ULEZ to help improve air quality by reducing the number of vehicles on the road that do not meet emissions standards. According to Transport for London, the central London ULEZ reduced harmful nitrogen oxides by 35% and particulate matter by 15% in central London within the first 10 months of its introduction.

In a study published on 5 September in the International Journal of Behavioral Nutrition and Physical Activity, a team led by researchers at the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ�� of London examined the impact of the ULEZ on how children travelled to school. ̽��ֱ��research was part of the CHILL study (Children’s Health in London and Luton).

̽��ֱ��study examined data from almost 2,000 children aged 6 to 9 years attending 84 primary schools in London and the control area, Luton. 44 schools were located with catchment areas within or bordering London’s ULEZ, and these were compared to a similar number in Luton and Dunstable (acting as a comparison group). ̽��ֱ��inclusion of the comparison site enabled the researchers to draw more robust conclusions and increased confidence in attributing the observed changes to the introduction of the ULEZ.

̽��ֱ��researchers collected data from the period June 2018 to April 2019, prior to ULEZ implementation, and again in the period June 2019 to March 2020, the year after implementation of the ULEZ but prior to COVID-19-related school closures.

Among those children in London who travelled by car prior to the introduction of the ULEZ, 4 in 10 (42%) switched to active modes, while one in 20 (5%) switched from active to inactive modes.

In contrast, only one in 5 (20%) children in Luton swapped from car travel to active modes, while a similar number (21%) switched from active to car travel. This means that children in London within the ULEZ were 3.6 times as likely to shift from travelling by car to active travel modes compared to those children in Luton and far less likely (0.11 times) to switch to inactive modes.

̽��ֱ��impact of the ULEZ on switching to active travel modes was strongest for those children living more than half a mile (0.78km) from school. This was probably because many children who live closer to school already walked or cycled to school prior to the ULEZ and therefore there was more potential for change in those living further away from their school.

̽��ֱ��study’s first author, Dr Christina Xiao from the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��introduction of the ULEZ was associated with positive changes in how children travelled to school, with a much larger number of children moving from inactive to active modes of transport in London than in Luton.

“Given children's heightened vulnerability to air pollution and the critical role of physical activity for their health and development, financial disincentives for car use could encourage healthier travel habits among this young population, even if they do not necessarily target them.”

Joint senior author Dr Jenna Panter from the MRC Epidemiology Unit, ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��previous Government was committed to increasing the share of children walking to school by 2025 and we hope the new Government will follow suit. Changing the way children travel to school can have significant effects on their levels of physical activity at the same time as bringing other co-benefits like improving congestion and air quality, as about a quarter of car trips during peak morning hours in London are made for school drop-offs.”

After ULEZ was introduced in Central London, the total number of vehicles on the roads fell by 9%, and by one-third (34%) for vehicles that failed to meet the required exhaust emission standards, with no clear evidence of traffic moving instead to nearby areas.

Joint senior author Professor Chris Griffiths from the Wolfson Institute of Population Health, Queen Mary ̽��ֱ�� of London, said: “Establishing healthy habits early is critical to healthy adulthood and the prevention of disabling long term illness, especially obesity and the crippling diseases associated with it. ̽��ֱ��robust design of our study, with Luton as a comparator area, strongly suggests the ULEZ is driving this switch to active travel. This is evidence that Clean Air Zone intervention programmes aimed at reducing air pollution have the potential to also improve overall public health by addressing key factors that contribute to illness.”

Due to the introduction of COVID-19 restrictions in late March 2020, the study was paused in 2020/2021 and results are only reported for the first year of follow-up. However, as both London and Luton, the study areas, were similarly affected, the researchers believe this disruption is unlikely to have affected the results. ̽��ֱ��study has restarted following up with the children to examine the longer-term impacts of the ULEZ. This will identify if the changes they observed in the year following the introduction of the ULEZ persist.

̽��ֱ��study was conducted in collaboration with Queen Mary ̽��ֱ�� of London, Imperial College, ̽��ֱ�� of Bedfordshire, ̽��ֱ�� of Edinburgh, ̽��ֱ�� of Oxford and ̽��ֱ�� of Southern California and funded by the National Institute for Health and Care Research Public Health Research (NIHR), NIHR Applied Research Collaboration North Thames, and Cambridge Trust.

Reference
Xiao, C et al. Children’s Health in London and Luton (CHILL) cohort: A 12-month natural experimental study of the effects of the Ultra Low Emission Zone on children’s travel to school. IJBNPA; 5 Sept 2024; DOI: 10.1186/s12966-024-01621-7

Four in ten children in Central London who travelled to school by car switched to more active modes of transport, such as walking, cycling, or public transport, following the introduction of the Ultra-Low Emission Zone (ULEZ), according to new research. In the comparison area with no ULEZ, Luton, only two in ten children made this switch over the same period.

Changing the way children travel to school can have significant effects on their levels of physical activity at the same time as bringing other co-benefits like improving congestion and air quality

Jenna Panter

Matt Brown

ULEZ signs (cropped)

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Red and processed meat consumption associated with higher type 2 diabetes risk

Anonymous — Tue, 20 Aug 2024 22:30:56 +0000

̽��ֱ��findings are published today in ̽��ֱ��Lancet Diabetes and Endocrinology.

Global meat production has increased rapidly in recent decades and meat consumption exceeds dietary guidelines in many countries. Earlier research indicated that higher intakes of processed meat and unprocessed red meat are associated with an elevated risk of type 2 diabetes, but the results have been variable and not conclusive.

Poultry such as chicken, turkey, or duck is often considered to be an alternative to processed meat or unprocessed red meat, but fewer studies have examined the association between poultry consumption and type 2 diabetes.

To determine the association between consumption of processed meat, unprocessed red meat and poultry and type 2 diabetes, a team led by researchers at the ̽��ֱ�� of Cambridge used the global InterConnect project to analyse data from 31 study cohorts in 20 countries. Their extensive analysis took into account factors such as age, gender, health-related behaviours, energy intake and body mass index.

̽��ֱ��researchers found that the habitual consumption of 50 grams of processed meat a day - equivalent to 2 slices of ham - is associated with a 15% higher risk of developing type 2 diabetes in the next 10 years. ̽��ֱ��consumption of 100 grams of unprocessed red meat a day - equivalent to a small steak - was associated with a 10% higher risk of type 2 diabetes.

Habitual consumption of 100 grams of poultry a day was associated with an 8% higher risk, but when further analyses were conducted to test the findings under different scenarios the association for poultry consumption became weaker, whereas the associations with type 2 diabetes for each of processed meat and unprocessed meat persisted.

Professor Nita Forouhi of the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, and a senior author on the paper, said: “Our research provides the most comprehensive evidence to date of an association between eating processed meat and unprocessed red meat and a higher future risk of type 2 diabetes. It supports recommendations to limit the consumption of processed meat and unprocessed red meat to reduce type 2 diabetes cases in the population.

“While our findings provide more comprehensive evidence on the association between poultry consumption and type 2 diabetes than was previously available, the link remains uncertain and needs to be investigated further.”

InterConnect uses an approach that allows researchers to analyse individual participant data from diverse studies, rather than being limited to published results. This enabled the authors to include as many as 31 studies in this analysis, 18 of which had not previously published findings on the link between meat consumption and type 2 diabetes. By including this previously unpublished study data the authors considerably expanded the evidence base and reduced the potential for bias from the exclusion of existing research.

Lead author Dr Chunxiao Li, also of the MRC Epidemiology Unit, said: “Previous meta-analysis involved pooling together of already published results from studies on the link between meat consumption and type 2 diabetes, but our analysis examined data from individual participants in each study. This meant that we could harmonise the key data collected across studies, such as the meat intake information and the development of type 2 diabetes.

“Using harmonised data also meant we could more easily account for different factors, such as lifestyle or health behaviours, that may affect the association between meat consumption and diabetes.”

Professor Nick Wareham, Director of the MRC Epidemiology Unit, and a senior author on the paper said: “InterConnect enables us to study the risk factors for obesity and type 2 diabetes across populations in many different countries and continents around the world, helping to include populations that are under-represented in traditional meta-analyses.

“Most research studies on meat and type 2 diabetes have been conducted in USA and Europe, with some in East Asia. This research included additional studies from the Middle East, Latin America and South Asia, and highlighted the need for investment in research in these regions and in Africa.”

InterConnect was initially funded by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602068.

Reference
Li, C et al. Meat consumption and incident type 2 diabetes: a federated meta-analysis of 1·97 million adults with 100,000 incident cases from 31 cohorts in 20 countries. Lancet Diabetes Endocrinol.; 20 August 2024

Adapted form a press release from the MRC Epidemiology Unit

Meat consumption, particularly consumption of processed meat and unprocessed red meat, is associated with a higher type 2 diabetes risk, an analysis of data from almost two million participants has found.

Our research supports recommendations to limit the consumption of processed meat and unprocessed red meat to reduce type 2 diabetes cases in the population

Nita Forouhi

Lauri Patterson

Preparing a Monte Cristo Sandwich, with Black Forest Ham

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Ultra-processed food makes up almost two-thirds of calorie intake of UK adolescents

cjb250 — Wed, 17 Jul 2024 01:30:13 +0000

̽��ֱ��study found that UPF consumption was highest among adolescents from deprived backgrounds, those of white ethnicity, and younger adolescents.

UPFs are food items that are manufactured from industrial substances and contain additives such as preservatives, sweeteners, colourings, flavourings, and emulsifiers. UPFs vary greatly, but tend to indicate poor dietary quality, with higher levels of added sugars, saturated fat, and sodium, as well as decreased fibre, protein, and micronutrient content. They have been suggested as one of the key drivers of the global rise in diseases such as obesity, type 2 diabetes, and cancer.

Globally, the availability and sales of UPFs have increased over time and previous evidence suggests that this has led to increased consumption among adolescents. To look at trends within the UK, researchers from Cambridge and Bristol analysed data from four-day food diaries of almost 3,000 adolescents in the UK National Diet and Nutrition Survey between 2008/09 and 2018/19.

In research published today in the European Journal of Nutrition, the researchers found that a mean of 66% of adolescents’ energy intake came from UPF consumption during this period, though there was a slight fall from 68% to 63% between 2008/09 and 2018/2019.

Parents’ occupation, ethnic group and UK region all influenced the proportion of calorie intake from UPFs:

Adolescents from disadvantaged backgrounds consumed a higher proportion of their calorie intake from UPFs compared to adolescents from less disadvantaged backgrounds (68.4% compared with 63.8%).
Adolescents from a non-white ethnicity consumed a lower proportion of their calorie intake from UPFs (59.0% compared with 67.3%).
Adolescents living in the North of England consumed a higher proportion of their calorie intake from UPFs compared with those living in the South of England and London (67.4% compared with 64.1%).
18-year-olds consumed a lower proportion of their calorie intake from UPFs compared with 11-year-olds (63.4% compared with 65.6%).

Dr Yanaina Chavez-Ugalde from the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, the study’s first author, said: “Adolescents’ food patterns and practices are influenced by many factors, including their home environment, the marketing they are exposed to and the influence of their friends and peers. But adolescence is also an important time in our lives where behaviours begin to become ingrained.

“It’s clear from our findings that ultra-processed foods make up the majority of adolescents’ diets, and their consumption is at a much higher level than is ideal, given their potential negative health impacts.”

̽��ֱ��researchers argue that the observed reduction in UPF intake pre-pandemic could be partly explained by an increased public awareness and health concerns associated with sugar consumption, government-led campaigns, sugar-taxes in other countries and the reformulation of sugary drinks to reduce their sugar content.

Dr Esther van Sluijs from the MRC Epidemiology Unit at Cambridge, joint senior author, said: “Ultra-processed foods offer convenient and often cheaper solutions to time- and income-poor families, but unfortunately many of these foods also offer poor nutritional value. This could be contributing to the inequalities in health we see emerging across childhood and adolescence.”

Dr Zoi Toumpakari from the Centre for Exercise, Nutrition and Health Sciences at the ̽��ֱ�� of Bristol, joint senior author, added: “Our findings suggest that disparities in consumption of ultra-processed foods are not just down to individual choices. We hope this evidence can help guide policymakers in designing more effective policies to combat the negative effects of ultra-processed food consumption among youth and the ripple effects this has on public health.”

This study was largely funded by the National Institute for Health and Care Research School for Public Health Research.

Reference
Chavez-Ugalde, Y et al. Ultra-processed food consumption in UK adolescents: distribution, trends, and sociodemographic correlates using the National Diet and Nutrition Survey 2008/09 to 2018/19. Eur J Nutr; 17 Jul 2024; DOI: 10.1007/s00394-024-03458-z

Adolescents consume around two-thirds of their daily calories from ultra-processed foods (UPFs), new research from the Universities of Cambridge and Bristol has found.

Ultra-processed foods make up the majority of adolescents’ diets, and their consumption is at a much higher level than is ideal, given their potential negative health impacts

Yanaina Chavez-Ugalde

Juanmonino (Getty Images)

Boy eating a burger

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Largest ever genetic study of age of puberty in girls shows links with weight gain

cjb250 — Mon, 01 Jul 2024 09:00:22 +0000

In the largest study of its kind to date, an international team led by researchers at the Medical Research Council (MRC) Epidemiology Unit, ̽��ֱ�� of Cambridge, studied the DNA of around 800,000 women from Europe, North America, China, Japan, and Korea.

Published on 1 July in Nature Genetics, the researchers found more than 1,000 variants – small changes in DNA – that influence the age of first menstrual period. Around 600 of these variants were observed for the first time.

̽��ֱ��age at which girls hit puberty and start having periods normally occurs between ages 10 to 15, though this has been getting earlier and earlier in recent decades. ̽��ֱ��reasons for this are not fully understood. Early puberty is linked with increased risk of a number of diseases in later life, including type 2 diabetes, cardiovascular disease, and certain cancers. Later puberty on the other hand, has been linked to improved health in adulthood and a longer lifespan.

Just under half (45%) of the discovered genetic variants affected puberty indirectly, by increasing weight gain in early childhood.

Corresponding author Professor John Perry said: “Many of the genes we’ve found influence early puberty by first accelerating weight gain in infants and young children. This can then lead to potentially serious health problems in later life, as having earlier puberty leads to higher rates of overweight and obesity in adulthood.”

Previous work by the team – together with researchers at Cambridge’s MRC Metabolic Diseases Unit – showed that a receptor in the brain, known as MC3R, detects the nutritional state of the body and regulates the timing of puberty and rate of growth in children, providing a mechanism by which this occurs. Other identified genes appeared to be acting in the brain to control the release of reproductive hormones.

̽��ֱ��scientists also analysed rare genetic variants that are carried by very few people, but which can have large effects on puberty. For example, they found that one in 3,800 women carry variants in the gene ZNF483, which caused these women to experience puberty on average, 1.3 years later.

Dr Katherine Kentistou, lead study investigator, added: “This is the first time we’ve ever been able to analyse rare genetic variants at this scale. We have identified six genes which all profoundly affect the timing of puberty. While these genes were discovered in girls, they often have the same impact on the timing of puberty in boys. ̽��ֱ��new mechanisms we describe could form the basis of interventions for individuals at risk of early puberty and obesity.”

̽��ֱ��researchers also generated a genetic score that predicted whether a girl was likely to hit puberty very early or very late. Girls with the highest 1% of this genetic score were 11 times more likely to have extremely delayed puberty – that is, after age 15 years. On the other hand, girls with the lowest 1% genetic score were 14 times more likely to have extremely early puberty – before age 10.

Senior author and paediatrician Professor Ken Ong said: “In the future, we may be able to use these genetic scores in the clinic to identify those girls whose puberty will come very early or very late. ̽��ֱ��NHS is already trialling whole genome sequencing at birth, and this would give us the genetic information we need to make this possible.

“Children who present in the NHS with very early puberty – at age seven or eight – are offered puberty blockers to delay it. But age of puberty is a continuum, and if they miss this threshold, there’s currently nothing we have to offer. We need other interventions, whether that’s oral medication or a behavioural approach, to help. This could be important for their health when they grow up.”

̽��ֱ��research was supported by the Medical Research Council and included data from the UK Biobank.

Reference
Kentistou, KA & Kaisinger, LR, et al. Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nat Gen; 1 July 2024; DOI: 10.1038/s41588-024-01798-4

Genes can indirectly influence the age at which girls have their first period by accelerating weight gain in childhood, a known risk factor for early puberty, a Cambridge-led study has found. Other genes can directly affect age of puberty, some with profound effects.

Many of the genes we’ve found influence early puberty by first accelerating weight gain in infants and young children. This can then lead to potentially serious health problems in later life

John Perry

Halfpoint Images (Getty Images)

Portrait of a young girl writing in her diary

Yes

Moving our bodies - and mindsets

skbf2 — Fri, 07 Jun 2024 12:44:51 +0000

Moving your body and mind can help promote mental wellbeing in the workplace, say Cambridge researchers.

Cambridge experts awarded 2024 Academy of Medical Sciences Fellowships

cjb250 — Mon, 20 May 2024 23:01:02 +0000

Professor Nita Forouhi from the Medical Research Council (MRC) Epidemiology Unit and Professor Susan Gathercole from the Department of Psychiatry and MRC Cognition and Brain Sciences Unit join an esteemed Fellowship of over 1,400 researchers who have been recognised for their remarkable contributions to advancing biomedical and health sciences, ground-breaking research discoveries and translating developments into benefits for patients and wider society.

Professor Nita Forouhi is a clinical scientist whose research is focused on the link between diet, nutrition and the risk of diabetes, obesity and related disorders. She is Professor of Population Health and Nutrition and leads the Nutritional Epidemiology programme, which was awarded the Vice-Chancellor’s Best Impact Award in 2016. She frequently engages with the media to promote knowledge in the area of diet and health.

Professor Susan Gathercole is a cognitive psychologist with interests in memory and learning, including the causes of specific learning difficulties in children and how they might be overcome. Susan became a Fellow of the British Academy in 2014 and was awarded an OBE for services to psychology and education in 2016.

Professor Andrew Morris PMedSci, President of the Academy of Medical Sciences, said: “It is an honour to welcome these brilliant minds to our Fellowship. Our new Fellows lead pioneering work in biomedical research and are driving remarkable improvements in healthcare. We look forward to working with them, and learning from them, in our quest to foster an open and progressive research environment that improves the health of people everywhere through excellence in medical science.

“It is also welcoming to note that this year's cohort is our most diverse yet, in terms of gender, ethnicity and geography. While this progress is encouraging, we recognise that there is still much work to be done to truly diversify our Fellowship. We remain committed to our EDI goals and will continue to take meaningful steps to ensure our Fellowship reflects the rich diversity of the society we serve."

̽��ֱ��new Fellows will be formally admitted to the Academy at a ceremony on Wednesday 18 September 2024.

Two Cambridge Fellows are among the new Academy of Medical Sciences Fellows announced today.

Academy of Medical Sciences

Academy of Medical Sciences logo

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Scientists identify rare gene variants that confer up to 6-fold increase in risk of obesity

Anonymous — Thu, 04 Apr 2024 12:36:17 +0000

̽��ֱ��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.

̽��ֱ��study, published in Nature Genetics, was led by researchers at the Medical Research Council (MRC) Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the ̽��ֱ�� of Cambridge.

̽��ֱ��researchers used UK Biobank and other data to perform whole exome sequencing of body mass index (BMI) in over 500,000 individuals.

They found that genetic variants in the gene BSN, also known as Bassoon, can raise the risk of obesity as much as six times and was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes.

̽��ֱ��Bassoon gene variants were found to affect 1 in 6,500 adults, so could affect about 10,000 people in the UK.

̽��ֱ��brain’s role in obesity

Obesity is a major public health concern as it is a significant risk factor for other serious diseases, including cardiovascular disease and type 2 diabetes, yet the genetic reasons why some people are more prone to weight gain are incompletely understood.

Previous research has identified several obesity-associated gene variants conferring large effects from childhood, acting through the leptin-melanocortin pathway in the brain, which plays a key role in appetite regulation.

However, while both BSN and APBA1 encode proteins found in the brain, they are not currently known to be involved in the leptin-melanocortin pathway. In addition, unlike the obesity genes previously identified, variants in BSN and APBA1 are not associated with childhood obesity.

This has led the researchers to believe that they may have uncovered a new biological mechanism for obesity, different to those we already know for previously identified obesity gene variants.

Based on published research and laboratory studies they report in this paper, which indicate that BSN and APBA1 play a role in the transmission of signals between brain cells, the researchers suggest that age-related neurodegeneration could be affecting appetite control.

Professor John Perry, study author and an MRC Investigator at the ̽��ֱ�� of Cambridge, said: “These findings represent another example of the power of large-scale human population genetic studies to enhance our understanding of the biological basis of disease. ̽��ֱ��genetic variants we identify in BSN confer some of the largest effects on obesity, type 2 diabetes and fatty liver disease observed to date and highlight a new biological mechanism regulating appetite control.”

̽��ֱ��use of global data

̽��ֱ��accessibility of large-scale databases such as UK Biobank has enabled researchers to search for rare gene variants that may be responsible for conditions including obesity.

For this study, the researchers worked closely with AstraZeneca to replicate their findings in existing cohorts using genetic data from individuals from Pakistan and Mexico. This is important as the researchers can now apply their findings beyond individuals of European ancestry.

If the researchers can better understand the neural biology of obesity, it could present more potential drug targets to treat obesity in the future.

Dr Slavé Petrovski, VP of the Centre for Genomics Research at AstraZeneca, said: “Rigorous large-scale studies such as this are accelerating the pace at which we uncover new insights into human disease biology. By collaborating across academia and industry, leveraging global datasets for validation, and embedding a genomic approach to medicine more widely, we will continue to improve our understanding of disease – for the benefit of patients.”

Next steps for research

Professor Giles Yeo, study author based at the MRC Metabolic Diseases Unit, added: “We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen, but perhaps more importantly, that the variation in Bassoon is linked to adult-onset and not childhood obesity. Thus these findings give us a new appreciation of the relationship between genetics, neurodevelopment and obesity.”

Reference
Zhao, T et al. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease. Nat Gen; 4 Apr 2024; DOI: 10.1038/s41588-024-01694-x

Adapted from a press release from the Medical Research Council

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

We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen

Giles Yeo

World Obesity Federation

Woman with obesity washing food

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