Why do some people grow to be giants while others only grow to modest proportions? In the largest genome-wide association study to date, researchers have uncovered the genetic factors behind the increase in size. In doing so, the highly complex basis of this trait became clear once again: The team has identified more than 12,000 genetic variants that are linked to human body size. The results could contribute to the understanding of growth disorders. In addition, the study can stimulate further investigations into traits and diseases with complex genetic bases, say the scientists.
Assessment matter! Many characteristics of a person are pre-programmed from birth - they are based on certain genetic factors that are inherited. There are characteristics that are based on individual or only a few special features in the genome. Others, on the other hand, are shaped by a smorgasbord of different genetic variations. This is particularly the case with human height, as previous studies have shown. Many genetic variants have already been identified that are linked to differences in human body size. But it became apparent that the actual extent of possible genetic influencing factors is far greater.
Enormous scope of study
An international team of researchers is now presenting the most comprehensive study on the subject to date. While the largest genome-wide body size association study to date was based on a sample size of around 700,000 people, the current study now includes genetic analyzes of more than five million people. Of these, 76 percent were predominantly of European descent, while approximately one million had an African, East Asian, Hispanic, or South Asian background. In addition to the genetic information, the height of all study participants was known. This enabled so-called genotyping, on which association studies are based: the scientists were able to use statistical methods to show the connection between genetic characteristics and different body sizes.
In this way, they have now identified 12,111 gene variants that are linked to body size. When they examined their positions in the genome, they found that they are particularly often located near genetic areas that are already known to be associated with growth disorders. The scientists believe that the variations discovered now account for a large proportion of all variants associated with body size, particularly in the populations of European descent. Specifically, they probably explain about 40 percent of the differences in body size. For people with a non-European background, on the other hand, there are probably still many undiscovered variations due to the smaller amount of data, the researchers say.
The fact that the study included more than a million people of non-European descent was already more than usual for genetic studies - but there is room for improvement on this aspect, the scientists say. "While this is a success, the data is still biased too heavily towards people of European descent, a well-known problem in genetic studies," says first author Loic Yengo from the University of Queensland in Brisbane.
What the insights could bring
As the researchers explain, the new insights into the genetics of height growth also have a meaning that goes beyond basic research: Because the new results, the genetic profile of a person can in turn provide indications of their height. The information could thus also help to examine non-genetics-based factors that also influence height. Specifically, it may become possible to identify people who don't reach their genetically predicted height, which could help diagnose hidden diseases or disorders that stunt their growth or harm their health. Another possible application could be in forensics: the information could be used in police investigations to predict the height of a suspect at a crime scene based on a DNA sample.
However, the researchers also see groundbreaking importance in their work: It is becoming clear that genome-wide association studies can contribute to clarifying the causes of characteristics or diseases that can be traced back to a very broad genetic basis. "Genomic studies are revolutionary and could hold the key to solving many global health problems - their potential is tremendously exciting," says co-first author Eirini Marouli from Queen Mary University of London. "If we can get a clearer picture of a trait like height at the genomic level, we might have a model that we can use to better diagnose and treat gene-driven diseases like heart disease or schizophrenia," says the scientist.
Source: Queen Mary University of London, University of Queensland, Article: Nature, doi: Nature 10.1038/s41586-022-05275-y