A study conducted by the International Genetic Investigation of Anthropometric Traits (GIANT) Consortium, provides a better insight into the biology of height. It also offers a model for investigating traits and diseases that are typically caused by many common gene changes acting together. The findings of the study were published online on October 5th by Nature Genetics. It is the largest genome-wide association study (GWAS) that has been conducted till date and involves more than 300 institutions and more than 250,000 subjects which is roughly double (around 400) the number of known gene regions which influences height.
Joel Hirschhorn, MD, PhD, of Boston Children’s Hospital and the Broad Institute of MIT and Harvard, leader of the GIANT Consortium and co-senior investigator on the study said that height is almost completely determined by genetics. However, the studies that have been conducted in the field were only able to explain just about 10% of this genetic influence. By doubling the number of participants in the study, the scientists are now able to have a much more complete picture of how common genetic variations have an influence on the height. It can also be ascertained to an extent how many genetic variants are there and how much influence they have.
Hundreds of GIANT investigators shared and analyzed data from the genomes of 253,288 people. They carried out the herculean task of checking about two million common genetic variants which showed up in at least 5 percent of their subjects. From this pool, 697 were chosen in 424 gene regions and were said to be related to height. This is the largest number to be associated with any trait or disease. With the results of this study, about 20% of the heritability of height can be explained.
The previous studies has hinted that a large number of genes influence height, and also pointed that the majority of heritability comes from common genetic variants, not rare ones. Since, the sample size was not big enough; a definitive conclusion could not be drawn. That is why it was decided to double the sample size; this way one is able to make new discoveries.
Co-senior investigator Peter Visscher, PhD, of the University of Queensland, Australia remarked that the study narrows down the genomic regions that contain a substantial proportion of remaining variationto be discovered with even larger sample sizes. It is understood that height is a model trait that could explain how human genetics works since this trait is not determined by one by many. It is estimated that 80% of height is due to genes.
Hirschhorn added that the result of the study was to prioritize many genes and pathways as important in skeletal growth during childhood. That is why it needed a collaborative model, to get the work done.
In 2007 the first paper was published that identified the first common height gene, and today the research team has identified nearly 700 genetic variants that determine height. It was seen that a number of the 697 height-related genetic variants were located near genes that were known to be involved in growth. However, there were also plenty of surprises as well. There were some pathways that had not been identified in previous studies but were important. Many of the genes identified in this research are likely to be important regulators of skeletal growth, but had not been known until now. As the sample size grows, there are more surprises from biology.