UNDER STRICT EMBARGO UNTIL TUESDAY 13 MAY 2025 AT 10AM UK TIME
Peer reviewed | Observational study | People
The results of an international study led by researchers from Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) shed new light the underlying biological mechanisms which cause differences in health risks, symptoms and outcomes between males and females.
The study, carried out in collaboration with the Berlin Institute of Health at Charité, Universitätsmedizin Berlin, and the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, was published today in Nature Communications. Using data from UK Biobank and the Fenland study, the team carried an in-depth analysis of the genetic links between ~6,000 proteins and hundreds of diseases in 56,000 males and females.
The team found that for two-thirds of these proteins, their levels differed between males and females. Further examination revealed that only a very small fraction, around 100 proteins out of the 6,000 studied, had differences in the genetic ‘switches’ which control their levels, when compared between males and females.
These findings, which may have implications for drug development, indicate that while there are differences between the sexes in relation to how much they express certain proteins, what’s causing these differences isn’t solely down to differences in their genetics.
Instead, the authors highlight the importance of looking beyond genetics – and other medical factors such as hormones – when comparing health risks and outcomes between males and females. Their findings indicate that non-medical factors such as where people work and live, their education, financial situation, access to resources, as well as their lifestyle also contribute to the health differences experiences between the sexes and so should be explored further and considered more when exploring sex differences in health.
Mine Koprulu, lead author of the study and a postdoctoral researcher at Queen Mary’s PHURI, said: “For the first time in history, we are able to study human biology at this level of detail—across genes, proteins, and more. This is the largest study to date exploring the similarities and differences in how our genetic code regulates blood protein levels between sexes. Our findings highlight the need to better understand the factors that impact health differences — at the genetic level and beyond— to create more tailored and equitable healthcare for everyone.”
Professor Claudia Langenberg, Director of the PHURI at Queen Mary and Professor of Computational Medicine at the Berlin Institute of Health at Charité, Germany, said: “Drug development pipelines increasingly incorporate information on genetic differences in protein levels and function and this has led to large investment in human cohorts, such as UK Biobank. From this perspective, better understanding of population differences in the regulation of proteins, such as those between males and females, is essential to guide precision medicine approaches and identify where one size may not fit all. Our results clearly show that with very few exceptions, protein regulating genetic variants identified so far behave in a very similar way in males and females. This provides evidence for an important implicit assumption – that insights arising from studying these variants apply to both sexes.”
In this study, data was categorised as male or female based on chromosomal information (XX or XY). The authors acknowledge that chromosomal information does not always align with an individual’s gender identity. However, for the purposes of this study (genetic and protein-level scientific analyses), this categorisation was necessary, and data on gender identity was not reliably recoded meaning it could not be consistently used across all data.
ENDS
NOTES TO EDITORS
Contact
Honey Lucas
Faculty Communications Officer – Medicine and Dentistry
Queen Mary University of London
Email: h.lucas@qmul.ac.uk or press@qmul.ac.uk
Paper details:
Mine Koprulu, et al. “Sex differences in the genetic regulation of the human plasma proteome.” Published in Nature Communications.
DOI: 10.1038/s41467-025-59034-4
Available after publication at: https://www.nature.com/articles/s41467-025-59034-4
Under strict embargo until 10AM (UK time) on Tuesday 13 May 2025.
A copy of the paper is available upon request.
Conflicts of interest: Eleanor Wheeler is now an employee of AstraZeneca. The remaining authors declare no competing interests.
Funded by:
The Fenland Study (DOI 10.22025/2017.10.101.00001) is funded by the Medical Research Council (MC_UU_12015/1, Claudia Langenberg, Nicholas J. Wareham).
This work is supported by the Medical Research Council (MC_UU_00006/1 - Aetiology and Mechanisms) (Claudia Langenberg, Eleanor Wheeler, Maik Pietzner, Nicola D. Kerrison, and Nicholas J. Wareham).
Mine Koprulu is supported by Gates Cambridge Trust.
Harry Hemingway is supported by Health Data Research UK and the NIHR University College London Hospitals Biomedical Research Centre.
Spiros Denaxas is supported by a) the BHF Data Science Centre led by HDR UK (grant SP/19/3/34678), b) BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement 116074, c) the NIHR Biomedical Research Centre at University College London Hospital NHS Trust (UCLH BRC), d) a BHF Accelerator Award (AA/18/6/24223), e) the CVD-COVID-UK/COVID-IMPACT consortium and f) the Multimorbidity Mechanism and Therapeutic Research Collaborative (MMTRC, grant number MR/V033867/1).
Julia Carrasco-Zanini was supported by a 4-year Wellcome Trust PhD Studentship and the Cambridge Trust. We are grateful for all the participants from Fenland Study and UK Biobank cohort who have enabled this work.
About Queen Mary
At Queen Mary University of London, we believe that a diversity of ideas helps us achieve the previously unthinkable.
Throughout our history, we’ve fostered social justice and improved lives through academic excellence. And we continue to live and breathe this spirit today, not because it’s simply ‘the right thing to do’ but for what it helps us achieve and the intellectual brilliance it delivers.
Our reformer heritage informs our conviction that great ideas can and should come from anywhere. It’s an approach that has brought results across the globe, from the communities of east London to the favelas of Rio de Janeiro.
We continue to embrace diversity of thought and opinion in everything we do, in the belief that when views collide, disciplines interact, and perspectives intersect, truly original thought takes form.
About the MRC Epidemiology Unit
The MRC Epidemiology Unit is a department at the University of Cambridge. It is working to improve the health of people in the UK and around the world. Obesity, type 2 diabetes and related metabolic disorders present a major and growing global public health challenge. These disorders result from a complex interplay between genetic, developmental, behavioural and environmental factors that operate throughout life. The mission of the Unit is to investigate the individual and combined effects of these factors and to develop and evaluate strategies to prevent these diseases and their consequences.
About the Medical Research Council
The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. The Medical Research Council is part of UK Research and Innovation.
About the University of Cambridge
The University of Cambridge is one of the world’s leading universities, with a rich history of radical thinking dating back to 1209. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence.
The University comprises 31 autonomous Colleges and over 100 departments, faculties and institutions. Its 24,000 students include around 9,000 international students from 147 countries. In 2023, 73% of its new undergraduate students were from state schools and more than 25% from economically disadvantaged backgrounds.
Cambridge research spans almost every discipline, from science, technology, engineering and medicine through to the arts, humanities and social sciences, with multi-disciplinary teams working to address major global challenges. In the Times Higher Education’s rankings based on the UK Research Excellence Framework, the University was rated as the highest scoring institution covering all the major disciplines.
A 2023 report found that the University contributes nearly £30 billion to the UK economy annually and supports more than 86,000 jobs across the UK, including 52,000 in the East of England. For every £1 the University spends, it creates £11.70 of economic impact, and for every £1 million of publicly-funded research income it receives, it generates £12.65 million in economic impact across the UK.
The University sits at the heart of the ‘Cambridge cluster’, in which more than 5,000 knowledge-intensive firms employ more than 71,000 people and generate £21 billion in turnover. Cambridge has the highest number of patent applications per 100,000 residents in the UK.
Journal
Nature Communications
Method of Research
Observational study
Subject of Research
People
Article Title
Mine Koprulu, et al. “Sex differences in the genetic regulation of the human plasma proteome.”
Article Publication Date
13-May-2025
COI Statement
Eleanor Wheeler is now an employee of AstraZeneca. The remaining authors declare no competing interests.