In the largest study of its kind, scientists reveal that differences in male and female health go far beyond genetics — pointing to a more complex mix of biology, environment and society.
Key Points at a Glance
- Researchers analyzed ~6,000 proteins and their links to disease across 56,000 individuals
- Two-thirds of proteins differed in levels between males and females
- But genetic regulation of proteins was nearly identical in both sexes
- Study urges deeper focus on lifestyle, environment and social factors in sex-based health gaps
For decades, scientists have known that men and women often experience disease differently — from risk factors to symptoms and outcomes. But what actually causes these differences? According to a landmark international study led by Queen Mary University of London, the answers are far more complex than just our genetic code.
Published in Nature Communications, the study analyzed genetic and protein-level data from 56,000 participants across the UK Biobank and Fenland studies. Working in collaboration with the Berlin Institute of Health at Charité and the University of Cambridge’s MRC Epidemiology Unit, the researchers set out to explore how sex-linked differences in protein levels relate to health risks and disease outcomes.
The team looked at nearly 6,000 proteins — essential molecules in the blood that play key roles in everything from immune response to metabolism. They found that two-thirds of these proteins differ in concentration between men and women. At first glance, this seemed to confirm that male and female biology is fundamentally different.
But then came a twist: when the researchers examined genetic regulation — the molecular switches that control how much of each protein is produced — they found that only about 100 proteins (roughly 1.6%) showed sex-specific differences in genetic control.
In other words, while protein levels vary widely between sexes, the genetic instructions for regulating them are nearly the same.
“This is the largest study to date exploring the similarities and differences in how our genetic code regulates blood protein levels between sexes,” said Dr. Mine Koprulu, lead author and postdoctoral researcher at Queen Mary’s Precision Healthcare University Research Institute (PHURI). “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.”
If not genetics, then what’s behind these pronounced differences? The study’s authors suggest a broader set of influences: hormonal profiles, lifestyle, education, work environment, socioeconomic status, and access to resources may all contribute to how diseases manifest and progress differently between men and women.
Professor Claudia Langenberg, Director of PHURI and co-senior author, emphasized the implications for precision medicine — the fast-growing field of tailoring treatments to individuals. “Drug development pipelines increasingly incorporate information on genetic differences in protein levels and function. 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.”
Importantly, the study reaffirms an assumption long held in biomedical science: that most genetic insights apply similarly across sexes. This supports the continued use of large-scale, mixed-sex datasets in genomic research — while also stressing the need to interpret health data through a broader lens.
For example, while heart disease might present with chest pain in men, it may show up as fatigue or nausea in women — a difference often overlooked in clinical settings. Likewise, autoimmune diseases affect women at far higher rates, yet the genetic triggers remain elusive. Studies like this one show that the causes may not lie in DNA alone.
While the study used chromosomal information (XX or XY) to categorize sex, the authors acknowledge that this may not align with individual gender identity — a limitation shaped by available data, not ideology. Still, the insights gleaned offer a valuable roadmap for more inclusive and responsive healthcare in the future.
As Dr. Koprulu puts it: “For the first time in history, we are able to study human biology at this level of detail — across genes, proteins, and more. And we’re learning that biology is only part of the story.”
Source: Queen Mary University of London
