X Chromosome Linked to Differences in Height Between Sexes

Scientists studying the X chromosome have concluded that a small proportion, 1 to 2 percent, of the height difference between men and women can be blamed directly on the X chromosome.

The researchers from the University of Helsinki analyzed commonly occurring genetic variations in the X chromosome, one of the two sex-determining chromosomes, in almost 25,000 Northern European individuals, to explain differences in "twelve commonly studied cardiometabolic and anthropometric traits."

"Studying the X chromosome has some particular challenges. The fact that women have two copies of this chromosome and men only one has to be taken into account in the analysis. We nevertheless wanted to take up the challenge since we had a strong belief that opening 'the X files' for research would reveal new, interesting biological insights," said Dr. Taru Tukiainen, who is currently working at the Massachusetts General Hospital in Boston.

The study showed that a genetic variant close to ITM2A, a gene that has a role in cartilage development, is frequent among shorter than average individuals. The identified variant, which is present in more than a third of Europeans, was also shown to increase the expression of ITM2A, suggesting that the more the gene is expressed the shorter the person will be. Interestingly, the effect of this variant on height was shown to be much stronger in women.

"The double dose of X-chromosomal genes in women could cause problems during the development. To prevent this, there is a process by which one of the two copies of the X chromosome present in the cell is silenced. When we realized that the height associated variant we identified was nearby a gene that is able to escape the silencing we were particularly excited," explained Professor Samuli Ripatti, the principal investigator behind the study.

The study is available in PLOS Genetics.