Context:

A recent study published in the Proceedings of the National Academy of Sciences (PNAS) analysed genetic data from over 9 lakh individuals using three major biobanks. The study provided rare evidence on how variations in sex chromosomes affect height.

Chromosome Variations and Height:

The study compared individuals with additional X or Y chromosomes. Findings included:

• An extra Y chromosome led to a greater increase in height than an extra X chromosome.
• This pattern was consistent across various population groups, suggesting a strong genetic influence.

·         Researchers used statistical models to isolate the role of sex chromosomes from hormonal influences and known conditions like Turner and Klinefelter syndromes.

·         The results showed that genetic contribution from the Y chromosome explains up to 22.6% of the average height difference between men and women.

The study also ties into broader societal and health issues:

• Over the past century, men have gained height faster than women.
• Social preferences often favor taller men, though researchers caution that taller individuals may face increased risks for certain cancers, due to more frequent cell division.

SHOX Gene and Its Function:

The SHOX (Short Stature Homeobox) gene regulates bone growth and is located in the pseudoautosomal region 1 (PAR1)—a segment shared by both the X and Y chromosomes.

• In females (XX), one X chromosome is mostly inactive, but genes in PAR1 (including SHOX) remain partially active.
• In males (XY), both the X and Y chromosomes actively express the SHOX gene, resulting in higher gene activity and greater height potential.

Other conditions related to SHOX:

When one copy of SHOX gene is missing or not working properly (a condition called SHOX haploinsufficiency), it can lead to short stature and certain skeletal problems.

SHOX haploinsufficiency is known to cause short stature in the following conditions:

• Turner Syndrome
• Leri–Weill Syndrome (LWS)
• Some cases of idiopathic short stature (short stature with no known cause)

Conclusion:

While hormones remain important for growth, this study confirms that sex-linked genetic factors—especially SHOX gene expression—play a major role in explaining height differences between men and women. These findings strengthen the understanding of sex-based biological variation and offer a foundation for further genetic research related to growth and health outcomes.