I married my wife because I love her, and she completes me in many ways. That said, one of the benefits was that while I was average in height, she was taller, so I hoped that breeding for height might be at play. A study in PNAS shows the folly in that presumptive benefit.
“Sex-related differences are observed for many medical phenotypes, from autoimmune conditions which disproportionately affect females to the strong male predominance in autism spectrum disorder.”
While the media pushes our attention to disparities in gender-related sports performance, there are some significant complexities of the disparities that gender brings. Height is easily measured and a good metric to consider because it is a “normally distributed” trait, and adult males are generally 5 inches taller than adult females. The underlying biology remains unknown.
A gene called SHOX, found on a shared region of the X and Y chromosomes, plays a role in determining height because it is essential to bone development. Both males (XY) and females (XX) usually have two working copies of this gene because PAR1, SHOX’s shared region, escapes the inactivation that affects one X chromosome in females. However, this escape is incomplete, meaning males may have higher overall SHOX activity. This height “advantage” does not seem to be mediated by sex hormones because adults with an XY chromosome set but no sex hormones are about 7 cm taller than those with XX chromosomes.
Combinatorial Confusion
Individuals may have fewer or more than the expected two sex chromosomes. Individuals with Turner’s syndrome, with only one X, and therefore only one copy of SHOX, are short in stature. Individuals with Klinefelter syndrome have an additional copy of SHOX and are generally taller. To add to the combinatorial confusion, the “gene dosage effect” varies depending on whether it is an X or Y gained or lost. These combinations, along with the impact of male sex hormones, were the knot the researchers sought to untie.
The dataset includes over 900,000 adult participants in genetically different biobanks. All the participants were measured, and their complement of sex chromosomes determined.
- After accounting for male sex hormones, 46,XY (males) participants were roughly 13 cm taller than 46,XX (females) in both European and African biobanks.
- Based on 1200 individuals with atypical numbers of sex chromosomes, the presence of an additional Y chromosome “tended to have a larger effect” than an additional X chromosome.
- In the typical case, 46,XY vs. 46,XX, the presence of the Y chromosome had an estimated impact of 22% on an individual’s height.
As for my personal experiment, one son is my height; the second is his mother’s. Mendel’s work on peas remains more theoretical than practicable. Of greater import is that the study demonstrates how individuals with more or fewer sex chromosomes, medically termed sex chromosomal aneuploids, “can facilitate the modeling of phenotypic variability in response to changes in sex chromosome dosage.”
More specifically, the researchers point to other studies they have performed demonstrating that for autism spectrum disorder (ASD), the Y chromosome plays an outsized role, helping to explain the finding of a nearly 4-fold greater incidence of ASD among males. This technique may be helpful for other sex-influenced diseases like autoimmune disorders.
The idea that height is all about hormones is officially outdated. This massive genetic study shows that sex chromosomes, especially the dosage of the SHOX gene on X and Y, have a measurable, hormone-independent effect on height. So, while society obsesses over gender differences in sports, science reminds us that our chromosomes are quietly running the show behind the scenes—determining not just how tall we are but possibly our risks for conditions like autism and autoimmune disorders. If you’re counting on your partner’s tall genes to do the heavy lifting, you might want to recalibrate your expectations. Evolution’s roll of the dice is messier and more interesting than we imagined.
Source: X and Y gene dosage effects are primary contributors to human sexual dimorphism: The case of height PNAS DOI:10.1073/pnas.2503039122
Chuck Dinerstein, MD, MBA
Director of Medicine
Dr. Charles Dinerstein, M.D., MBA, FACS is Director of Medicine at the American Council on Science and Health. He has over 25 years of experience as a vascular surgeon.
