A large-scale international study involving 700,000 participants has revealed 83 genetic variations controlling human height. 

It is well-known that above-average-height parents often have above-average-height children just as below-average-height parents often have below-average-height children. Indeed, this observation suggests that parent-to-child transmission of genetic information is the primary factor that determines an individual's height.

To discover the 83 genetic variations, the research team measured the presence of 250,000 genetic variations in the study's 700,000 participants - an enormous job.

"Of these 83 genetic variations, some influence adult height by more than 2 centimetres, which is enormous," said Guillaume Lettre, a professor at Université de Montréal's Faculty of Medicine. "The genes affected by these genetic variations modulate, among other things, bone and cartilage development and growth hormone production and activation." 

Human height as a starting point for precision medicine

"In our study, we used adult height as a simple observable physical trait to understand how information in our DNA can explain how we are all different," said Lettre. "The idea was that if we could understand the genetics of human height, we could then apply this knowledge to develop genetic tools to predict other traits or the risk of developing common diseases."

Which people will have a heart attack before age 55 despite having a healthy lifestyle? Which children will develop leukemia, and how will they respond to treatment? Questions like these are at the heart of precision medicine, an emerging approach to healthcare that involves customizing treatment and prevention to the individual patient. The results of this study on human height could help to identify genetic variations that influence the risk of developing human diseases, the researchers believe. Eventually, these variations will be valuable tools for practioners of precision medicine to use.

The genetics of human height and of growth problems

In regards to height, the researchers found several genes that may represent good therapeutic targets for growth problems often observed in children. For example, they demonstrated that variations that inactivate the gene STC2 increase the height of individuals who carry them in their DNA by acting on certain growth factors. "In this sense, evaluating whether drugs that block STC2 activity could have an impact on growth seems to us very promising," concluded Lettre.

Citation: Joel N. Hirschhorn, Panos Deloukas, Guillaume Lettre, et al. "Rare and low-frequency coding variants alter human adult height", Nature, February 1st, 2017. DOI:10.1038/nature21039