03 February 2017
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Why am I shorter than you?

More than 200 scientists co-lead by Erasmus MC researchers assembled a study published in Nature with more than 700,000 participants to study changes in our DNA which lead to differences in height.


Adult height is mostly determined by the information encoded in our DNA: children from tall parents tend to be taller, and vice versa. “The idea is that if we can understand the genetics of a simple human trait like height, we could then apply this knowledge to develop tools to predict more complex human diseases such as diabetes or schizophrenia”, says Carolina Medina-Gomez, Erasmus MC post-doctoral researcher and co-first author of the publication.

Genome-wide association studies have identified along the last decade hundreds of DNA changes – called single nucleotides polymorphisms (SNPs) – that influence human height, all with weak effects of no more than 1mm. Furthermore, these DNA changes were for the most part located in regulatory regions of the human DNA that do not encode proteins, rendering difficult the identification of the genes that control height in humans.


This new study, which was conducted in cooperation with BBMRI-NL, focused on DNA changes that alter the structure of proteins. The researchers found 83 of them, which influence height considerably, some of which by more than 2 cm. “Considering that we brought ¾ of a million participants together in a highly collaborative effort we anticipated new discoveries to come, but the impact of this SNPs on height is just remarkable”, says Fernando Rivadeneira, co-director of the study and Associate Professor at Erasmus MC.

“Many of these DNA changes are located in genes implicated in growth hormone or bone biology, but many also highlight new biological processes that modulate human stature. As an example, carriers of a variation in the STC2 gene (seen in 9 out of every 10,000 people) are 1-2 cm taller. The study demonstrated also how the presence of this variation increases the levels of circulating growth factors in the blood, opening new avenues for the treatment of disorders of growth.”


The large-scale study also serves as a model to understand common diseases (like diabetes, cancer and heart disease) where the size of patient collections is far smaller. Demonstrating that DNA variants of large effect exist in a reduced fraction of carriers is a strong proof-of-concept of the type of knowledge needed for the personalized medicine approach.
See the article in Nature: ‘Rare and low-frequency coding variants alter human adult height’.

Text and image courtesy of Erasmus MC