Scientists have long known that height is mostly hereditary, but even the geneticists who set out to study height two decades ago weren't certain they'd ever be able to find the common genetic factors influencing this trait.
- By ALLESSANDRA DiCORATO | Broad Institute
Now, by studying the DNA of 5.4 million people, a team led by those same geneticists has done what they thought years ago would be impossible.
In the largest study of its kind to date, members of the GIANT consortium - including researchers at the Broad Institute of MIT and Harvard, Harvard Medical School, and Boston Children's Hospital - have identified more than 12,000 genetic variants that influence height.
These variants explain 10 percent to 40 percent of all variation in height, depending on a person's ancestry. They cluster around parts of the genome involved in skeletal growth.
The team said that because of its unprecedented size, the study has uncovered the vast majority of the genetic variants linked to height and is the capstone of a 20-year effort.
"We feel that this is really a milestone," said co-senior author Joel Hirschhorn, HMS professor of genetics, the HMS Concordia Professor of Pediatrics at Boston Children's Hospital, and leader of the GIANT consortium. "We'd been studying height for a while but had only identified a small fraction of common variant heritability."
"We're now basically done mapping this heritability to specific genomic regions," he added, "and that highlights what increasing sample size can tell us about traits controlled by multiple genes."
Hirschhorn said that the findings, published in Nature on Oct. 12, could one day help physicians identify individuals who aren't reaching their genetically predicted height and might have a hidden disease or deficiency affecting their growth and health.
The results illustrate the power of genome-wide association studies, or GWAS, to uncover the biological basis and, in larger studies, the heritability of disease.
Heritable height
In 2000, as a pediatric endocrinology fellow at Boston Children's, Hirschhorn saw many children who had been referred by their pediatricians for unusually short stature.
He would often tell parents their child was growing slowly because of the genes the child inherited.
Though scientists estimated that genes contributed to 80 percent of variation in height, they didn't know what those genes were.
"After about the 20th patient, I thought, Hey, I'm working in a place that can figure this out," he said. As a postdoctoral researcher at the Broad Institute, Hirschhorn decided then to study height, though everyone told him height was too polygenic - there were too many genes involved to be able to find them.
Undeterred, Hirschhorn turned to GWAS: studies in which scientists scan whole genomes in a population to identify associations between genetic variants and traits.
