Height study casts light on genetic mechanisms

Published 25 October 2010

An extensive global gene-mapping project has identified a large number of loci that dictate whether a person is tall or short. The aim of the project is to find out more about how many genes interact to form biologically interesting mechanisms behind diseases. "Height on its own is perhaps not tremendously interesting but it serves as a good indicator when determining how genetic mechanisms work", says Martin Ridderstråle, Lund University Diabetes Centre, who is one of the researchers behind the study, the results of which were recently published in the highly respected journal Nature.

Easy to measure
Height has several important advantages in genetic studies. Firstly, it is highly heritable, which is evidenced by the fact that short parents as a rule have short children and tall parents have tall children. Secondly, a large number of genes are involved. The researchers identified 180 different genetic loci, 100 of which were previously unknown. "Another advantage is that height is easy to measure, with a high degree of accuracy", adds Martin Ridderstråle.

Complex interactions

A large number of common diseases, such as type 2 diabetes and obesity, are caused by complex interactions between many genes and lifestyle and other environmental factors. "Height is an easier matter. We know that approximately 80 per cent of the variance in height is determined by hereditary factors, and the rest by the environment, for example diet," Martin Ridderstråle explains.

The extreme and the common

There are two principal ways of identifying genes that raise disease risk: "One is to look for rare variants which mean that carriers run the risk of becoming very fat, for example, but these are uncommon and don’t say very much about the excess weight that many people carry. The other way is to try to identify variants that are common in the population but where each variant has only a very small effect. It’s only when a person carries multiple risk alleles that the impact is evident at individual level", says Martin Ridderstråle.

Relevant genetic loci

The research group chose the second approach when examining the genetics of height. More than 180　000 individuals took part in the study. From the large amount of data, 180 relevant genetic loci were selected. Five of these where strongly associated with loci that have previously been related with different diseases, such as osteoporosis, rheumatoid arthritis, type 1 diabetes, and obesity.

Biological signal pathways
"The study confirms that large mapping projects reveal patterns for the concerned genes. If this is possible for height, it’s also possible for disease", explains Martin Ridderstråle. "The next step is to find out how the genes form biologic signalling pathways and mechanisms behind diseases", he concludes.

Link to publication in Nature
Hundreds of variants clustered in genomic loci and biological pathways affect human height

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09410.html

Text: Tord Ajanki/Camilla Franks