Tall or short? Rare genes explain differences in human height

Scientists have identified 83 new rare genetic variants that influence human height, in what is the largest research about human height to date. Despite their low frequency, these genes appear to have a very significant impact on how tall people are, offering new insights into human skeletal growth and growth disorders.

Height is a complex genetic trait that is largely inherited. The role of environmental factors is considered to be relatively minor.

"Compared to other traits, height receives a very high contribution of genes and this is why it can be a model for large genetic studies. Some environmental factors like diet may also contribute to height, but to a lesser extent", co-author Panagiotis Deloukas, from Queen Mary University of London, told IBTimes UK.

Although the link between genes and height is indisputable, how babies grow into adults and what influences skeletal growth remain poorly understood, with many variants thought to be playing a role.

The study now published in Nature looked at the genome of more than 700 000 people from a database known as the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium. This has led to the discovery of the 83 rare variants, bringing the total of genetic variants known to be involved in human height to around 700.

Target for growth disorders

Among the new variants identified by the scientists, 51 were "low-frequency" variants, found in less than 5 percent of people, and 32 rare variants, found in less than 0.%. Nevertheless, their effect was very important, and some of the variants could account for differences in height of up to 2cm – over 10 times the average effect of previously discovered gene variants.

This was the case of two variants of a gene known as STC2, which made people 1 to 2cm taller on average than non-carriers. This gene's pathway could thus serve as a potential therapeutic target for people with growth disorders resulting in short sizes.

Many of the variants have been identified in genes that were already known to be playing a role in skeletal growth and in growth disorders, but they also pointed to potential new gene candidates and biological pathways previously unidentified as involved in bone development and skeletal growth.

'Poster child' of complex genetic traits

The study may also provide new insights into other traits and common disorders that, like height, depend on a number of genetic variants. Height is considered to be a simple and valuable model for understanding traits produced by not one gene, but many.

"Height is a very good trait to study because it is highly heritable and can be very accurately measured compared to other complex genetic traits like blood pressure, which can vary. Our findings can shed a light on the potentially important role of rare variants to complex genetic traits and common diseases, such as diabetes or cardiovascular diseases", Deloukas said.

Furthermore, this research shows the importance of having large samples of participants to identify rare variants that can be helpful in understanding diseases like diabetes.

"Other studies published on common diseases suggested there was a paucity of rare variants, but the scientists had looked at much smaller samples of people. Our study can help improve future studies' designs, and the strong message is that big sample size are needed to identify interesting rare genetic variants", he added.