A tall story: Great strides in identifying genetic factors in height

A study which examined data on DNA from more than 250,000 people, published on October 6 in Nature Genetics, roughly doubles the number of known genome regions involved in height to more than 400. It also revealed that more than half of the factors involved in determining height are explained by simple common genetic variation - the sort of genetic variation that exists in more than 1 in 10 people.

The collaboration, co led by the University of Exeter Medical School and part-funded by the Wellcome Trust, involved more than 450 experts from well over 300 institutions in Australia, the USA and several European countries. Together, they form the aptly named GIANT consortium. The study is the largest of its kind to date. They checked more than 2 million common genetic factors – those shared by at least five per cent of participants. From this they found 697 genetic variants in 424 regions of the genome that are related to height. The findings represent a massive stride forward in an area of research in which virtually nothing was known as recently as 2007.

Professor Tim Frayling, of the University of Exeter Medical School, oversaw the study. He said: “It’s common knowledge that people born to tall parents are more likely to be tall themselves. Most of this is down to the variations in our DNA sequence that we inherit from our parents - the different versions of all our genes. In 2007 we published the first paper that identified the first common height gene, and since then the research has come on leaps and bounds. We have now identified nearly 700 genetic variants that are involved in determining height. This goes a long way towards fulfilling a scientific curiosity that could have real impact in the treatment of diseases that can be influenced by height, such as osteoporosis, cancer or heart disease. It also a step forward towards a test that may reassure parents worried that their child is not growing as well as they'd hoped - most of these children have probably simply inherited a big batch of "short genes"."

Height is determined by a very large, but finite, number of contributing factors. Genetic causes are located throughout the genome, and environmental factors such as diet also play a role. The GIANT consortium is working towards identifying the thousands of hidden factors which have varying effects in height, ranging from minute to gigantic. The results arise from analysis of DNA data on 253,288 individuals of European ancestry. The research team says increasing sample sizes of this magnitude make it far easier to find commonalities that determine traits such as size.

Lead author Dr Andrew Wood, of the University of Exeter Medical School, said: “Our findings have helped to identify a large proportion of the genetic architecture that contributes to determining our height. We know that as a population we have become taller over the last few generations, because of factors including improved nutrition. But more than 80 per cent of the factors in height variation are known to be down to genetics, with the rest caused by environmental factors. Thanks to advances in technology, we now have access to far greater quantities of DNA data. These data sets are proving to be a genetic treasure trove which has enabled us to shed light on height, and we expect to continue to make significant advances, both in this field and in other human traits. Our results suggest that massive human genetic studies, possibly into the millions, will continue to uncover all the subtle effects of our genetic variation that influence our health, behaviour, body shape and all aspects of what makes us who we are.”

Dr Joel Hirschhorn, of Boston Children’s Hospital and the Broad Institute of MIT and Harvard, is leader of the GIANT Consortium and co-senior investigator on the study. Dr Hirschhorn said: “When you double the sample size and increase your statistical power, you can make new discoveries. Our results prioritise many genes and pathways as important in skeletal growth during childhood. Without a highly collaborative model, there’s no way we could get this work done. We can now explain about 20 percent of the heritability of height, up from about 12 percent where we were before.”

Professor Peter Visscher, of the University of Queensland, Australia, said: “The study narrows down the genomic regions that contain a substantial proportion of remaining variation—to be discovered with even larger sample sizes.”

Professor Frayling said: “The genes and pathways involved in height should help facilitate future studies, and we have made them publicly available to this end. We believe that large genetic studies could yield similarly rich lists in a variety of other traits, and could generate new biological hypotheses and motivate future research into the basis of human biology and disease.”

Height chart picture via Shutterstock.