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83 rare genes influence height, says GIANT

06 February 2017

By Jamie Rickman

Appeared in BioNews 887

A large international study has uncovered 83 rare genetic variants that can significantly affect a person's height.

Some variants resulted in a 2 cm height difference, compared with just 1 mm difference linked to more common variants, and one variant identified is a potential drug target for short stature. The variants were identified by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium in the most extensive study on height to date.

'Overall, we still think the majority of height genetics is due to common variants,' said Joel Hirschhorn, professor of paediatrics and genetics at Boston Children's Hospital, the co-senior investigator of the study. 'This study shows that at least some of height is due to rare variants and, for people who carry them, it can affect their height to a greater degree.'

Height is a trait which is mainly inherited, with environmental factors playing a relative minor role. Preliminary research by GIANT had identified nearly 700 common genetic variants linked to height. However, common variants are typically found outside protein-coding regions of DNA, making the affected genes difficult to discern.

Using a technology called ExomeChip, GIANT looked for 200,000 known rarer variants found inside protein-coding regions. The study involved over 700,000 participants and over 270 research groups.

They identified 83 genes previously unconnected with height, of which 51 were found in less than five percent of the population, and 32 in less than 0.5 percent. The traits control processes such as bone and cartilage development and growth hormone production, giving insight into the processes by which height is determined.

One variant found in less than 0.1 percent of the population was connected to a protein that could be a potential drug target for short stature.

'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,' Panagiotis Deloukas, professor of cardiovascular genomics at Queen Mary University of London and co-author of the study, told the International Business Times.

'Our study can help improve future studies' designs, and the strong message is that big sample sizes are needed to identify interesting rare genetic variants,' he added.

Following this study, 27.4 percent of the heritability of height is now accounted for.

'We probably won't get all of the way to explaining 100 percent of the genetic factors, but in some sense that's not really our goal,' said Professor Hirschhorn to NPR. 'Our goal is to use the genetics to do our best at understanding the biology.'

The study appeared in the journal Nature.

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