First robust genetic link to height in humans identified

Over a century ago, scientists first proposed that height is a complex trait — one influenced by environmental factors and multiple genes. While subsequent studies revealed that most of the variation in adult height is genetically determined, there has been little success in pinpointing the responsible genes. Some clues have come from rare syndromes of extreme height or shortness caused by severe alterations in specific gene sequences, but by and large, these changes do not explain the normal spectrum of human height.

Now researchers have uncovered the first genetic difference to be reproducibly associated with stature in the general population. The work, published in the September 2 advance online edition of Nature Genetics, is the result of an international collaboration led by researchers at the Broad Institute of Harvard and MIT, Children’s Hospital Boston, the University of Oxford, and Peninsula Medical School, Exeter, and that included researchers from the University of Helsinki, Lund University, the Finland National Public Health Institute, and the University of Bristol.

The research team used a new genome-wide association method to scan the DNA of thousands of people for single-letter differences — single nucleotide polymorphisms, or SNPs — in the genetic code that occur more often in taller people compared to shorter people. The scan zeroed in on a single-letter difference, either a ‘C’ or ‘T’, in the HMGA2 gene that accounted for an estimated 0.3% of the height variation among study participants. Compared to individuals with two ‘T’-containing copies of the gene, those with one ‘C’-containing copy of the gene tended to be taller by roughly half a centimeter, and those with two copies were nearly a centimeter taller on average.