What is it about?

Males and females often differ in traits like height, but the reasons behind these differences aren’t fully understood. Typically, females have two X chromosomes, while males have one X and one Y chromosome. Genetic content on the X or Y chromosomes may shape differences between the sexes. This study used height as a model trait to investigate how the X and Y chromosomes contribute to sex differences, as height is reliably recorded in healthcare, shows a strong and consistent difference between sexes, and is not fully explained by hormones related to sex determination. The heights of nearly one million individuals — including many with atypical numbers of X and Y chromosomes, a condition known as sex chromosome aneuploidy — were compared to isolate the relationship between X and Y chromosome dosage and height, independent of sex hormones.

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Why is it important?

This research showed that a Y chromosome contributes more to height than a second X chromosome does, independent of sex hormones. This difference accounts for approximately 22.6%, or 3.1 centimeters, of the average height gap between typical men and women. The results support the hypothesis that a gene called SHOX, which is found on both the X and Y chromosomes and is known to influence height, plays a key role in the height difference. Despite being found on both the X and Y chromosomes, SHOX is less active on the second X chromosome in females, whereas it is fully active on both the X and Y chromosomes in males. This difference in SHOX activity may explain a significant portion of the height difference between the sexes.

Perspectives

It is surprising that the question “Why are men generally taller than women?” is still not fully answered. My hope is that this study brings us one step closer to finally solving that mystery. While height is a biologically interesting trait, the methods used here can also help us understand other clinically important sex-based differences — such as why some diseases, including autoimmune diseases and neuropsychiatric disorders, affect males and females differently.

Alexander Berry
Geisinger Commonwealth School of Medicine

Read the Original

This page is a summary of: X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height, Proceedings of the National Academy of Sciences, May 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2503039122.
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