Milestone study answers genetic mysteries of human height
The results of the world's largest ever gene study have been published, revealing almost all the genetic variants that influence a person's height. The study involved analyzing DNA from more than five million people and ultimately homed in on 12,000 variants that play a role in how tall we are.
The new study, published in Nature, is the fruit of nearly 20 years of work from an international team of researchers. Joel Hirschhorn, from the Broad Institute, was one of the first researchers to start working on the project in the early 2000s.
According to Hirschhorn, many suspected height was far too complex a trait to ever fully understand. Even though it was well understood that height was a trait primarily determined by genetics, it was evident that hundreds, or even thousands, of gene variants likely played a role in the trait. And to catalog such a complex trait would require the kind of massive dataset that is simply impossible to gather.
Fifteen years ago conducting a genome-wide association study (GWAS) on just 1,000 people was a challenging and time-consuming task. So while it seemed hypothetically possible complex traits such as height could be predicted through genetic studies, not even Hirschhorn thought enough data could be gathered to be successful this quickly.
“Even the most optimistic among us didn’t think we’d get this big this fast,” Hirschhorn said. “When it became apparent that GWAS would be possible, I used to make sure in every talk I said, ‘there’s no way we’re going to get enough information that this will add to what we can do clinically to predict adult height.' But we succeeded beyond our wildest dreams. So now I get the chance to prove myself wrong.”
The new study reports on a massive GWAS involving DNA from nearly 5.4 million people, and found 12,111 genetic variants that can be associated with a person's height. Instead of being widely spread across the entire genome, as some had predicted, these height-influencing gene variants tended to cluster across regions covering only 20% of the genome.
While the findings are certainly a landmark scientific achievement, Hirschhorn does suggest there are clinical uses to this knowledge. At some point in the future a genetically predicted height score could be added to routine childhood health tracking. This would allow doctors to detect children who may be growing at a slower rate than their genetically determined height, indicating a possible problem or undiagnosed disease hindering their development.
The success of these findings also validate the idea that complex genetic traits can be effectively gauged using GWAS techniques as long as the dataset is big enough. Of course, height is a relatively simple trait to easily measure and correlate with millions of genetic records. Other more complex things like diseases such as depression or schizophrenia will prove much more challenging to genetically study but these results do prove it isn't impossible if large enough sample sizes can be gathered.
The biggest limitation to these new findings is the lack of diversity in the DNA data. Around four million of the samples were from people of European ancestry, meaning the results are only completely accurate for certain populations. Even though over one million participants were from diverse locations covering Africa, Asia and South America, more samples would be necessary to develop accurate genetic height predictions for those groups.
“Genomic studies are revolutionary and might hold the key to solving many global health challenges – their potential is tremendously exciting," said co-first author on the study Erin Marouli. "If we can map specific parts of the genome to certain traits, it opens the door to widespread targeted, personalized treatments further down the line that could benefit people everywhere.”
The new study was published in Nature.