Scientists identify more than 400 genes that influence height

In what is the largest genome-wide association study so far, an international research team has found more than 400 genes that influence height - nearly doubling the number of height-related genes identified in previous research.

Approximately 80% of height variation is genetic. The remaining 20% is thought to be influenced by environmental and lifestyle factors.

The researchers say their findings, reached by analyzing genome-wide data from more than 250,000 people, can explain around 20% of height heritability in humans, increasing from 12% prior to this study.

The study also narrows down the genomic regions that contain a substantial proportion of remaining variation - to be discovered with even larger sample sizes.

The researchers publish their findings in the journal Nature Genetics.

Height is a model characteristic for determining the mechanisms behind human genetics, according to the investigators. 

It particularly helps improve understanding of traits that are produced by multiple genes. They note that height is simple to measure, and approximately 80% of height variation is genetic. The remaining 20% is thought to be influenced by environmental and lifestyle factors.

Previous studies have suggested that height is influenced by lots of genes, most of which come from common genetic variants rather than rare ones. But the investigators involved in this latest research say that these studies have not been large enough to confirm such findings.

697 genetic variants in 424 genetic regions linked to height

With this in mind, the researchers set up the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. This involved analyzing the genomic data of 253,288 individuals from more than 300 worldwide institutions.

The team searched approximately 2 million genetic variants that were present in at least 5% of participants. From this, they identified 697 genetic variants located in 424 genetic regions that were linked to height.

Some of the genes identified as being linked to height came as a surprise, according to the researchers. They point to a gene called mTOR as an example. This gene has previously been associated with cellular growth, but it had never before been associated with skeletal growth.

Commenting on the findings, Dr. Hirschhorn, of Boston Children's Hospital and the Broad Institute of Massachusetts Institutes of Technology (MIT) and Harvard University in Cambridge, MA, says:

"There were some pathways that we knew were important, but had not come out in previous genome-wide association studies.

Many of the genes we identified are likely to be important regulators of skeletal growth, but were not known to be involved until now. Some may also be responsible for unexplained syndromes of abnormal skeletal growth in children. As you increase the sample size, you get more biology."

The researchers have no doubt that the larger sample size in the GIANT study helped lead to the discovery of many more height-related genes, and they believe that similar-sized studies in the future could do the same.

Going forward, the GIANT team plans to analyze genetic variants that occur among less than 5% of subjects and search for genetic variants that are present in the non-coding parts of genes.

Earlier this year, researchers reported on a study claiming that a genetic variant in chromosome Xmay explain why men and women differ in height.